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Keywords = gingival squamous cell carcinoma

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9 pages, 2443 KiB  
Case Report
A Case of Application of Computer-Aided Design and Manufacturing Technology and Extended Reality Surgical Assistance to Marginal Mandibulectomy
by Takahiro Nakada, Masahide Koyachi, Keisuke Sugahara, Akihiro Nishiyama, Mana Kawakami, Shintaro Nakajima, Kotaro Tachizawa, Kento Odaka, Satoru Matsunaga, Maki Sugimoto and Akira Katakura
J. Clin. Med. 2025, 14(1), 8; https://doi.org/10.3390/jcm14010008 - 24 Dec 2024
Viewed by 272
Abstract
Background/Objectives: Mandibular gingival squamous cell carcinoma (SCC) is the second most common oral cancer after tongue cancer. As these carcinomas often invade the mandible early, accurately defining the resection extent is important. This report highlights the use of preoperative virtual surgery data, computer-aided [...] Read more.
Background/Objectives: Mandibular gingival squamous cell carcinoma (SCC) is the second most common oral cancer after tongue cancer. As these carcinomas often invade the mandible early, accurately defining the resection extent is important. This report highlights the use of preoperative virtual surgery data, computer-aided design and manufacturing (CAD/CAM) technology, surgical guidance, and extended reality (XR) support in achieving highly accurate marginal mandibulectomy without recurrence or metastasis. Methods: CT imaging data obtained a month before surgery were imported into Materialize Mimics and Materialize Magics (Materialize, Leuven, Belgium, Ver22.0) CAD/CAM software and used to design an osteotomy guide. An STL file was generated, and the guide was fabricated using a 3D printer (Objet 260 Connex; Stratasys Ltd., Eden Prairie, MN, USA) prior to the operation. An XR application, installed on a HoloLens (Microsoft, WA, USA) head-mounted display, projected a hologram onto the surgical field. Results: The rapid intraoperative diagnostic tests were negative, and histopathology confirmed SCC without vascular or perineural invasion. No complications, including occlusal or feeding problems and sensory abnormalities, were observed. Postoperative imaging 3 years later showed no recurrence. Conclusions: Combining CAD/CAM and XR techniques for mandibulectomy may improve surgical accuracy and safety in oral and maxillofacial surgeries, whereas in-house 3D printing aids in managing tumor progression. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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14 pages, 9190 KiB  
Article
Parishin A Inhibits Oral Squamous Cell Carcinoma via the AKT/mTOR Signaling Pathway
by Lei Ma, Zhibin Liu, Eungyung Kim, Ke Huang, Chae Yeon Kim, Hyeonjin Kim, Kanghyun Park, Woo-Sung Kwon, Sang In Lee, Yong-Gun Kim, Youngkyun Lee, So-Young Choi, Haibo Zhang and Myoung Ok Kim
Pharmaceuticals 2024, 17(10), 1277; https://doi.org/10.3390/ph17101277 - 26 Sep 2024
Viewed by 913
Abstract
Background: Oral squamous cell carcinoma (OSCC) is an aggressive cancer with limited treatment options. Parishin A, a natural compound derived from Gastrodia elata, possesses multiple therapeutic properties. However, its effects on OSCC remain unexplored. Purpose: This study explores the anti-cancer potential of [...] Read more.
Background: Oral squamous cell carcinoma (OSCC) is an aggressive cancer with limited treatment options. Parishin A, a natural compound derived from Gastrodia elata, possesses multiple therapeutic properties. However, its effects on OSCC remain unexplored. Purpose: This study explores the anti-cancer potential of Parishin A on OSCC and its mechanisms. Methods: OSCC cell lines YD-10B and Ca9-22 were treated with varying Parishin A concentrations. Cell viability was detected using the CCK-8 assay, and colony formation was evaluated in agarose gel. Migration and invasion ability were assessed through wound healing and Matrigel invasion assays. The protein expression levels involved in the PI3K/AKT/mTOR signaling pathway and epithelial–mesenchymal transition (EMT) markers were examined via Western blotting. Results: Parishin A inhibited OSCC cell viability in both dose- and time-dependent manners, with significant reductions at 20, 40, 60, and 80 μM, without affecting normal human gingival fibroblasts. Colony formation decreased substantially at ≥40 μM higher Parishin A concentrations in a dose-dependent manner. Also, migration and invasion assays showed significant suppression by Parishin A treatment concentration ≥40 μM in a dose-dependent manner, as evidenced by decreased wound closure and invasion. Western blot analyses revealed increased E-cadherin levels and decreased N-cadherin and vimentin levels, suggesting EMT inhibition. Parishin A also decreased the phosphorylation levels of PI3K, AKT, and mTOR. Conclusion: Collectively, these findings support the potential of Parishin A as an anti-OSCC agent. Full article
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19 pages, 4248 KiB  
Article
Predicting Leukoplakia and Oral Squamous Cell Carcinoma Using Interpretable Machine Learning: A Retrospective Analysis
by Salem Shamsul Alam, Saif Ahmed, Taseef Hasan Farook and James Dudley
Oral 2024, 4(3), 386-404; https://doi.org/10.3390/oral4030032 - 13 Sep 2024
Viewed by 1419
Abstract
Purpose: The purpose of this study is to assess the effectiveness of the best performing interpretable machine learning models in the diagnoses of leukoplakia and oral squamous cell carcinoma (OSCC). Methods: A total of 237 patient cases were analysed that included [...] Read more.
Purpose: The purpose of this study is to assess the effectiveness of the best performing interpretable machine learning models in the diagnoses of leukoplakia and oral squamous cell carcinoma (OSCC). Methods: A total of 237 patient cases were analysed that included information about patient demographics, lesion characteristics, and lifestyle factors, such as age, gender, tobacco use, and lesion size. The dataset was preprocessed and normalised, and then separated into training and testing sets. The following models were tested: K-Nearest Neighbours (KNN), Logistic Regression, Naive Bayes, Support Vector Machine (SVM), and Random Forest. The overall accuracy, Kappa score, class-specific precision, recall, and F1 score were used to assess performance. SHAP (SHapley Additive ExPlanations) was used to interpret the Random Forest model and determine the contribution of each feature to the predictions. Results: The Random Forest model had the best overall accuracy (93%) and Kappa score (0.90). For OSCC, it had a precision of 0.91, a recall of 1.00, and an F1 score of 0.95. The model had a precision of 1.00, recall of 0.78, and F1 score of 0.88 for leukoplakia without dysplasia. The precision for leukoplakia with dysplasia was 0.91, the recall was 1.00, and the F1 score was 0.95. The top three features influencing the prediction of leukoplakia with dysplasia are buccal mucosa localisation, ages greater than 60 years, and larger lesions. For leukoplakia without dysplasia, the key features are gingival localisation, larger lesions, and tongue localisation. In the case of OSCC, gingival localisation, floor-of-mouth localisation, and buccal mucosa localisation are the most influential features. Conclusions: The Random Forest model outperformed the other machine learning models in diagnosing oral cancer and potentially malignant oral lesions with higher accuracy and interpretability. The machine learning models struggled to identify dysplastic changes. Using SHAP improves the understanding of the importance of features, facilitating early diagnosis and possibly reducing mortality rates. The model notably indicated that lesions on the floor of the mouth were highly unlikely to be dysplastic, instead showing one of the highest probabilities for being OSCC. Full article
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13 pages, 1856 KiB  
Article
Differential Expression of DNA Methyltransferase (DNMT1 and DNMT3), Histone Deacetylase (HDAC1 and HDAC2), and Upstream Target Regulators MiR-145 and Mir-152 among Oral Cancers
by Trevor Holloway and Karl Kingsley
Targets 2024, 2(3), 224-236; https://doi.org/10.3390/targets2030013 - 18 Aug 2024
Viewed by 841
Abstract
Epigenetic modulation of DNA and histones facilitated by and histone deacetylases (HDAC) is associated with the development and progression of many cancers, although less is known about DNA methyltransferase (DNMT) in oral cancers and the regulation of these targets. Using commercially available cell [...] Read more.
Epigenetic modulation of DNA and histones facilitated by and histone deacetylases (HDAC) is associated with the development and progression of many cancers, although less is known about DNA methyltransferase (DNMT) in oral cancers and the regulation of these targets. Using commercially available cell lines, oral squamous cell carcinomas (SCC4, SCC9, SCC15, SCC25, and CAL27), and normal gingival fibroblasts (HGF-1), growth assays and mRNA expression were evaluated using ANOVA. These results revealed homeostasis enzyme DNMT1 expression was significantly higher among slow-growing HGF-1 cells than among fast-growing oral cancers, p < 0.05. In contrast, DNMT3A and DNMT3B expression was significantly higher among oral cancers compared with HGF-1 cells, p < 0.05. However, differential expression of HDAC1 and HDAC2 was observed among SCC4, SCC25, and CAL27 cells. Further analysis of miR-152 (regulation and control of DNMT expression) and miR-21, miR-221, and miR-145 (regulation of HDAC expression) revealed all oral cancers produced miR-21, but none produced miR-221. However, differential expression of miR-145 (SCC15) and miR-152 (SCC25) suggested alternative epigenetic pathways and mechanisms of DNMT and HDAC regulation may be responsible for some of the observations revealed in this study. Full article
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12 pages, 1583 KiB  
Article
In Vitro Bioassay for Damage-Associated Molecular Patterns Arising from Injured Oral Cells
by Layla Panahipour, Chiara Micucci, Benedetta Gelmetti and Reinhard Gruber
Bioengineering 2024, 11(7), 687; https://doi.org/10.3390/bioengineering11070687 - 5 Jul 2024
Cited by 1 | Viewed by 1001
Abstract
Gingival fibroblasts are a significant source of paracrine signals required to maintain periodontal homeostasis and to mediate pathological events linked to periodontitis and oral squamous cell carcinomas. Among the potential paracrine signals are stanniocalcin-1 (STC1), involved in oxidative stress and cellular survival; amphiregulin [...] Read more.
Gingival fibroblasts are a significant source of paracrine signals required to maintain periodontal homeostasis and to mediate pathological events linked to periodontitis and oral squamous cell carcinomas. Among the potential paracrine signals are stanniocalcin-1 (STC1), involved in oxidative stress and cellular survival; amphiregulin (AREG), a growth factor that mediates the cross-talk between immune cells and epithelial cells; chromosome 11 open reading frame 96 (C11orf96) with an unclear biologic function; and the inflammation-associated prostaglandin E synthase (PTGES). Gingival fibroblasts increasingly express these genes in response to bone allografts containing remnants of injured cells. Thus, the gene expression might be caused by the local release of damage-associated molecular patterns arising from injured cells. The aim of this study is consequently to use the established gene panel as a bioassay to measure the damage-associated activity of oral cell lysates. To this aim, we have exposed gingival fibroblasts to lysates prepared from the squamous carcinoma cell lines TR146 and HSC2, oral epithelial cells, and gingival fibroblasts. We report here that all lysates significantly increased the transcription of the entire gene panel, supported for STC1 at the protein level. Blocking TGF-β receptor 1 kinase with SB431542 only partially reduced the forced expression of STC1, AREG, and C11orf96. SB431542 even increased the PTGES expression. Together, these findings suggest that the damage signals originating from oral cells can change the paracrine activity of gingival fibroblasts. Moreover, the expression panel of genes can serve as a bioassay for testing the biocompatibility of materials for oral application. Full article
(This article belongs to the Special Issue Tissue Engineering for Regenerative Dentistry)
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12 pages, 2190 KiB  
Article
Dimeric 3,5-Bis(benzylidene)-4-piperidones: Tumor-Selective Cytotoxicity and Structure-Activity Relationships
by Swagatika Das, Praveen K. Roayapalley, Hiroshi Sakagami, Naoki Umemura, Dennis K. J. Gorecki, Mohammad Hossain, Masami Kawase, Umashankar Das and Jonathan R. Dimmock
Medicines 2024, 11(1), 3; https://doi.org/10.3390/medicines11010003 - 11 Jan 2024
Viewed by 2139
Abstract
Background: The objective of this study is to find novel antineoplastic agents that display greater toxicity to malignant cells than to neoplasms. In addition, the mechanisms of action of representative compounds are sought. This report describes the cytotoxicity of a number of dimers [...] Read more.
Background: The objective of this study is to find novel antineoplastic agents that display greater toxicity to malignant cells than to neoplasms. In addition, the mechanisms of action of representative compounds are sought. This report describes the cytotoxicity of a number of dimers of 3,5-bis(benzylidene)-4-piperidones against human malignant cells (promyelocytic leukemia HL-60 and squamous cell carcinoma HSC-2, HSC-3, and HSC-4). Methods: Tumor specificity was evaluated by the selectivity index (SI), that is the ratio of the mean CC50 for human non-malignant oral cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) to that for malignant cells. Results: The compounds were highly toxic to human malignant cells. On the other hand, these molecules were less toxic to human non-malignant cells. In particular, a potent lead molecule, 3b, was identified. A QSAR study revealed that the placement of electron-releasing and hydrophilic substituents into the aryl rings led to increases in cytotoxic potencies. The modes of action of a lead compound discovered in this study designated 3b were the activation of caspases-3 and -7, as well as causing PARP1 cleavage and G2 arrest, followed by sub-G1 accumulation in the cell cycle. This compound also depolarized the mitochondrial membrane and generated reactive oxygen species in human colon carcinoma HCT116 cells. In conclusion, this study has revealed that, in general, the compounds described in this report are tumor-selective cytotoxins. Full article
(This article belongs to the Section Cancer Biology and Anticancer Therapeutics)
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18 pages, 5480 KiB  
Article
Immunomodulatory Effect of Hypericin-Mediated Photodynamic Therapy on Oral Cancer Cells
by Marcin Olek, Agnieszka Machorowska-Pieniążek, Zenon P. Czuba, Grzegorz Cieślar and Aleksandra Kawczyk-Krupka
Pharmaceutics 2024, 16(1), 42; https://doi.org/10.3390/pharmaceutics16010042 - 27 Dec 2023
Cited by 2 | Viewed by 1473
Abstract
In 2020, there were 377,713 new oral and lip cancer diagnoses and 177,757 deaths. Oral cancer is a malignancy of the head and neck region, and 90% of cases are squamous cell carcinomas (OSCCs). One of the alternative methods of treating pre-cancerous lesions [...] Read more.
In 2020, there were 377,713 new oral and lip cancer diagnoses and 177,757 deaths. Oral cancer is a malignancy of the head and neck region, and 90% of cases are squamous cell carcinomas (OSCCs). One of the alternative methods of treating pre-cancerous lesions and oral cancer is photodynamic therapy (PDT). In addition to the cytotoxic effect, an important mechanism of PDT action is the immunomodulatory effect. This study used the OSCC (SCC-25) cell line and the healthy gingival fibroblast (HGF-1) line. A compound of natural origin—hypericin (HY)—was used as the photosensitizer (PS). The HY concentrations of 0–1 µM were used. After two hours of incubation with PS, the cells were irradiated with light doses of 0–20 J/cm2. The MTT test determined sublethal doses of PDT. Cell supernatants subjected to sublethal PDT were assessed for interleukin 6 (IL-6), soluble IL-6 receptor alpha (sIL-6Ralfa), sIL-6Rbeta, IL-8, IL-10, IL-11 IL-20, IL-32, and Pentraxin-3 using the Bio-Plex ProTM Assay. The phototoxic effect was observed starting with a light dose of 5 J/cm2 and amplified with increasing HY concentration and a light dose. HY-PDT affected the SCC-25 cell secretion of sIL-6Rbeta, IL-20, and Pentraxin-3. HY alone increased IL-8 secretion. In the case of HGF-1, the effect of HY-PDT on the secretion of IL-8 and IL-32 was found. Full article
(This article belongs to the Special Issue Natural Products in Photodynamic Therapy)
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11 pages, 7474 KiB  
Case Report
Treatment Response of Gingival Squamous-Cell Carcinoma to Palliative Intent Immunotherapy
by Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson and James C. Gates
Curr. Oncol. 2023, 30(12), 10519-10529; https://doi.org/10.3390/curroncol30120767 - 18 Dec 2023
Viewed by 1922
Abstract
The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a [...] Read more.
The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is ongoing at 19 months from initiation. Patients #2 and 3 are each on treatment with single-agent pembrolizumab, with partial response of their tumors, minimal side effects, and ongoing response at 9 and 5 months of treatment, respectively. Durable clinical treatment response to palliative immunotherapy, as is evident in this report, warrants further consideration and investigation in the geriatric population. With appropriate patient selection, surgery may be avoided and allow patients to prioritize quality of life over curative intent surgery. Full article
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13 pages, 5063 KiB  
Article
Cytotoxicity, Differentiation, and Biocompatibility of Root-End Filling: A Comprehensive Study
by Ignacio Jimenez-Bueno, Rene Garcia-Contreras, Benjamin Aranda-Herrera, Hiroshi Sakagami, Christian Andrea Lopez-Ayuso, Hiroshi Nakajima, Carlos A. Jurado and Hamid Nurrohman
Biomimetics 2023, 8(7), 514; https://doi.org/10.3390/biomimetics8070514 - 29 Oct 2023
Cited by 1 | Viewed by 1773
Abstract
Assessing the biocompatibility of endodontic root-end filling materials through cell line responses is both essential and of utmost importance. This study aimed to the cytotoxicity of the type of cell death through apoptosis and autophagy, and odontoblast cell-like differentiation effects of MTA, zinc [...] Read more.
Assessing the biocompatibility of endodontic root-end filling materials through cell line responses is both essential and of utmost importance. This study aimed to the cytotoxicity of the type of cell death through apoptosis and autophagy, and odontoblast cell-like differentiation effects of MTA, zinc oxide–eugenol, and two experimental Portland cements modified with bismuth (Portland Bi) and barium (Portland Ba) on primary cell cultures. Material and methods: The cells corresponded to human periodontal ligament and gingival fibroblasts (HPLF, HGF), human pulp cells (HPC), and human squamous carcinoma cells from three different patients (HSC-2, -3, -4). The cements were inoculcated in different concentrations for cytotoxicity evaluation, DNA fragmentation in electrophoresis, apoptosis caspase activation, and autophagy antigen reaction, odontoblast-like cells were differentiated and tested for mineral deposition. The data were subject to a non-parametric test. Results: All cements caused a dose-dependent reduction in cell viability. Contact with zinc oxide–eugenol induced neither DNA fragmentation nor apoptotic caspase-3 activation and autophagy inhibitors (3-methyladenine, bafilomycin). Portland Bi accelerated significantly (p < 0.05) the differentiation of odontoblast-like cells. Within the limitation of this study, it was concluded that Portland cement with bismuth exhibits cytocompatibility and promotes odontoblast-like cell differentiation. This research contributes valuable insights into biocompatibility, suggesting its potential use in endodontic repair and biomimetic remineralization. Full article
(This article belongs to the Special Issue Biomimetic Remineralization on Enamel and Dentin: 2nd Edition)
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11 pages, 3087 KiB  
Article
Gingival Fibroblasts Are Sensitive to Oral Cell Lysates Indicated by Their IL11 Expression
by Layla Panahipour, Azarakhsh Oladzad Abbasabadi and Reinhard Gruber
Bioengineering 2023, 10(10), 1193; https://doi.org/10.3390/bioengineering10101193 - 13 Oct 2023
Cited by 1 | Viewed by 1324
Abstract
Damaged cells that appear as a consequence of invasive dental procedures or in response to dental materials are supposed to release damage-associated signals. These damage-associated signals not only support tissue regeneration but might also contribute to unwanted fibrosis. The aim of this study [...] Read more.
Damaged cells that appear as a consequence of invasive dental procedures or in response to dental materials are supposed to release damage-associated signals. These damage-associated signals not only support tissue regeneration but might also contribute to unwanted fibrosis. The aim of this study was to identify a molecular target that reflects how fibroblasts respond to necrotic oral tissue cells. To simulate the cell damage, we prepared necrotic cell lysates by sonication of the osteocytic cell line IDG-SW3 and exposed them to gingival fibroblasts. RNAseq revealed a moderate increase in IL11 expression in the gingival fibroblasts, a pleiotropic cytokine involved in fibrosis and inflammation, and also in regeneration following trauma. Necrotic lysates of the human squamous carcinoma cell lines HSC2 and TR146, as well as of gingival fibroblasts, however, caused a robust increase in IL11 expression in the gingival fibroblasts. Consistently, immunoassay revealed significantly increased IL11 levels in the gingival fibroblasts when exposed to the respective lysates. Considering that IL11 is a TGF-β target gene, IL11 expression was partially blocked by SB431542, a TGF-β receptor type I kinase inhibitor. Moreover, lysates from the HSC2, TR146, and gingival fibroblasts caused a moderate smad2/3 nuclear translocation in the gingival fibroblasts. Taken together and based on IL11 expression, our findings show that fibroblasts are sensitive to damaged oral tissue cells. Full article
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14 pages, 4913 KiB  
Article
A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs
by Tomoyuki Abe, Hiroshi Sakagami, Shigeru Amano, Shin Uota, Kenjiro Bandow, Yoshihiro Uesawa, Shiori U, Hiroki Shibata, Yuri Takemura, Yu Kimura, Koichi Takao, Yoshiaki Sugita, Akira Sato, Sei-ichi Tanuma and Hiroshi Takeshima
Medicines 2023, 10(7), 43; https://doi.org/10.3390/medicines10070043 - 14 Jul 2023
Cited by 2 | Viewed by 1992
Abstract
Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), [...] Read more.
Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds in comparison with four popular anti-cancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one order of magnitude higher TSM than newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two orders of magnitude lower TSE than Compounds A and B. Compounds A and B showed higher TSM, TSE, and TSN values than doxorubicin, 5-FU, and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that Compounds A and B may inhibit the signaling pathway of estrogen-related receptors. Full article
(This article belongs to the Section New Drugs Exploration and Development)
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18 pages, 6365 KiB  
Article
Synergistic Effects of New Curcumin Analog (PAC) and Cisplatin on Oral Cancer Therapy
by Abdelhabib Semlali, Sarra Beji, Ikram Ajala, Mohammed Al-Zharani and Mahmoud Rouabhia
Curr. Issues Mol. Biol. 2023, 45(6), 5018-5035; https://doi.org/10.3390/cimb45060319 - 8 Jun 2023
Cited by 14 | Viewed by 2398
Abstract
Oral cancer has traditionally been treated with surgery, radiotherapy, chemotherapy, or a combination of these therapies. Although cisplatin, a chemotherapy drug, can effectively kill oral cancer cells by forming DNA adducts, its clinical use is limited due to adverse effects and chemo-resistance. Therefore, [...] Read more.
Oral cancer has traditionally been treated with surgery, radiotherapy, chemotherapy, or a combination of these therapies. Although cisplatin, a chemotherapy drug, can effectively kill oral cancer cells by forming DNA adducts, its clinical use is limited due to adverse effects and chemo-resistance. Therefore, there is a need to develop new, targeted anticancer drugs to complement chemotherapy, allowing for reduced cisplatin doses and minimizing adverse effects. Recent studies have shown that 3,5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidine (PAC), a new curcumin analog, possesses anticancer properties and could be considered a complementary or alternative therapy. In this study, we aimed to assess the potential complementary effects of PAC in combination with cisplatin for treating oral cancer. We conducted experiments using oral cancer cell lines (Ca9-22) treated with different concentrations of cisplatin (ranging from 0.1 μM to 1 μM), either alone or in conjunction with PAC (2.5 and 5 μM). Cell growth was measured using the MTT assay, while cell cytotoxicity was evaluated using an LDH assay. Propidium iodide and annexin V staining were employed to examine the impact on cell apoptosis. Flow cytometry was used to investigate the effects of the PAC/cisplatin combination on cancer cell autophagy, oxidative stress, and DNA damage. Additionally, a Western Blot analysis was performed to assess the influence of this combination on pro-carcinogenic proteins involved in various signaling pathways. The results demonstrated that PAC enhanced the efficacy of cisplatin in a dose-dependent manner, leading to a significant inhibition of oral cancer cell proliferation. Importantly, treatment with PAC (5 μM) alongside different concentrations of cisplatin reduced the IC50 of cisplatin tenfold. Combining these two agents increased apoptosis by further inducing caspase activity. In addition, the concomitant use of PAC and cisplatin enhances oral cancer cell autophagy, ROS, and MitoSOX production. However, combined PAC with cisplatin inhibits the mitochondrial membrane potential (ΔΨm), which is a marker for cell viability. Finally, this combination further enhances the inhibition of oral cancer cell migration via the inhibition of epithelial-to-mesenchymal transition genes, such as E-cadherin. We demonstrated that the combination of PAC and cisplatin markedly enhanced oral cancer cell death by inducing apoptosis, autophagy, and oxidative stress. The data presented indicate that PAC has the potential to serve as a powerful complementary agent to cisplatin in the treatment of gingival squamous cell carcinomas. Full article
(This article belongs to the Section Molecular Medicine)
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17 pages, 4018 KiB  
Article
Synergistic Effect of Anethole and Platinum Drug Cisplatin against Oral Cancer Cell Growth and Migration by Inhibiting MAPKase, Beta-Catenin, and NF-κB Pathways
by Abdelhabib Semlali, Ikram Ajala, Sarra Beji, Mohammed Mousa Al-Zharani and Mahmoud Rouabhia
Pharmaceuticals 2023, 16(5), 700; https://doi.org/10.3390/ph16050700 - 5 May 2023
Cited by 12 | Viewed by 2466
Abstract
Cisplatin is a common drug used to treat patients with oral squamous cell carcinoma. However, cisplatin-induced chemoresistance poses a major challenge to its clinical application. Our recent study has shown that anethole possesses an anti-oral cancer effect. In this study, we examined the [...] Read more.
Cisplatin is a common drug used to treat patients with oral squamous cell carcinoma. However, cisplatin-induced chemoresistance poses a major challenge to its clinical application. Our recent study has shown that anethole possesses an anti-oral cancer effect. In this study, we examined the combined effect of anethole and cisplatin on oral cancer therapy. Gingival cancer cells Ca9-22 were cultured in the presence of various concentrations of cisplatin with or without anethole. The cell viability/proliferation and cytotoxicity were evaluated, respectively, by MTT, Hoechst staining, and LDH assay, while colony formation was measured by crystal violet. Oral cancer cell migration was evaluated by the scratch method. Apoptosis, caspase activity, oxidative stress, MitoSOX, and mitochondrial membrane potential (ΔΨm) levels were evaluated by flow cytometry, and the inhibition of signaling pathways was investigated by Western blot. Our results show that anethole (3 µM) potentiates cisplatin-induced inhibition of cell proliferation and decreases the ΔΨm on Ca9-22 cells. Furthermore, drug combination was found to inhibit cell migration and enhanced cisplatin cytotoxicity. The combination of anethole and cisplatin potentiates cisplatin-induced oral cancer cell apoptosis through the activation of caspase, while we also found anethole and cisplatin to enhance the cisplatin-induced generation of reactive oxygen species (ROS) and mitochondrial stress. In addition, major cancer signaling pathways were inhibited by the combination of anethole and cisplatin such as MAPKase, beta-catenin, and NF-κB pathways. This study reports that the combination of anethole and cisplatin might provide a beneficial effect in enhancing the cisplatin cancer cell-killing effect, thus lowering the associated side effects. Full article
(This article belongs to the Topic Advances in Anti-Cancer Drugs)
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14 pages, 4146 KiB  
Article
Effect of Hypericin-Mediated Photodynamic Therapy on the Secretion of Soluble TNF Receptors by Oral Cancer Cells
by Marcin Olek, Agnieszka Machorowska-Pieniążek, Zenon P. Czuba, Grzegorz Cieślar and Aleksandra Kawczyk-Krupka
Pharmaceutics 2023, 15(4), 1279; https://doi.org/10.3390/pharmaceutics15041279 - 19 Apr 2023
Cited by 5 | Viewed by 1799
Abstract
Squamous cell carcinoma is the most common cancer of the head and neck region. In addition to the classic surgical treatment method, alternative therapy methods are sought. One such method is photodynamic therapy (PDT). In addition to the direct cytotoxic effect, it is [...] Read more.
Squamous cell carcinoma is the most common cancer of the head and neck region. In addition to the classic surgical treatment method, alternative therapy methods are sought. One such method is photodynamic therapy (PDT). In addition to the direct cytotoxic effect, it is essential to determine the effect of PDT on persistent tumor cells. The study used the SCC-25 oral squamous cell carcinoma (OSCC) cell line and the HGF-1 healthy gingival fibroblast line. A compound of natural origin—hypericin (HY)—was used as a photosensitizer (PS) at concentrations of 0–1 µM. After two hours of incubation with the PS, the cells were irradiated with light doses of 0–20 J/cm2. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test was used to determine sublethal doses of PDT. Cell supernatants subjected to sublethal PDT were assessed for soluble tumor necrosis alpha receptors (sTNF-R1, sTNF-R2). The phototoxic effect was observed starting with a light dose of 5 J/cm2 and amplified with the increase in HY concentration and light dose. A statistically significant increase in sTNF-R1 secretion by SCC-25 cells was demonstrated after the PDT with 0.5 µM HY and irradiation with 2 J/cm2 (sTNF-R1 concentration = 189.19 pg/mL ± 2.60) compared to the control without HY and irradiated with the same dose of light (sTNF-R1 concentration = 108.94 pg/mL ± 0.99). The baseline production of sTNF-R1 was lower for HGF-1 than for SCC-25, and secretion was not affected by the PDT. The PDT had no effect on the sTNF-R2 production in the SCC-25 or HGF-1 lines. Full article
(This article belongs to the Special Issue Combination Approaches in Photodynamic Therapies for Cancer)
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17 pages, 5013 KiB  
Article
Oxidative Status Determines the Cytotoxicity of Ascorbic Acid in Human Oral Normal and Cancer Cells
by Wei-Zhi Huang, Ting-Ming Liu, Shu-Ting Liu, Ssu-Yu Chen, Shih-Ming Huang and Gunng-Shinng Chen
Int. J. Mol. Sci. 2023, 24(5), 4851; https://doi.org/10.3390/ijms24054851 - 2 Mar 2023
Cited by 4 | Viewed by 2363
Abstract
Oral squamous cell carcinoma (OSCC) can arise anywhere in the oral cavity. OSCC’s molecular pathogenesis is complex, resulting from a wide range of events that involve the interplay between genetic mutations and altered levels of transcripts, proteins, and metabolites. Platinum-based drugs are the [...] Read more.
Oral squamous cell carcinoma (OSCC) can arise anywhere in the oral cavity. OSCC’s molecular pathogenesis is complex, resulting from a wide range of events that involve the interplay between genetic mutations and altered levels of transcripts, proteins, and metabolites. Platinum-based drugs are the first-line treatment for OSCC; however, severe side-effects and resistance are challenging issues. Thus, there is an urgent clinical need to develop novel and/or combinatory therapeutics. In this study, we investigated the cytotoxic effects of pharmacological concentrations of ascorbate on two human oral cell lines, the oral epidermoid carcinoma meng-1 (OECM-1) cell and the Smulow–Glickman (SG) human normal gingival epithelial cell. Our study examined the potential functional impact of pharmacological concentrations of ascorbates on the cell-cycle profiles, mitochondrial-membrane potential, oxidative response, the synergistic effect of cisplatin, and the differential responsiveness between OECM-1 and SG cells. Two forms of ascorbate, free and sodium forms, were applied to examine the cytotoxic effect and it was found that both forms had a similar higher sensitivity to OECM-1 cells than to SG cells. In addition, our study data suggest that the determinant factor of cell density is important for ascorbate-induced cytotoxicity in OECM-1 and SG cells. Our findings further revealed that the cytotoxic effect might be mediated through the induction of mitochondrial reactive oxygen species (ROS) generation and the reduction in cytosolic ROS generation. The combination index supported the agonistic effect between sodium ascorbate and cisplatin in OECM-1 cells, but not in SG cells. In summary, our current findings provide supporting evidence for ascorbate to serve as a sensitizer for platinum-based treatment of OSCC. Hence, our work provides not only repurposing of the drug, ascorbate, but also an opportunity to decrease the side-effects of, and risk of resistance to, platinum-based treatment for OSCC. Full article
(This article belongs to the Special Issue Cytotoxicity, Antioxidant and Anticancer Activity of Natural Products)
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