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Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 12682

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Dr. Ming-Ju Hsieh

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Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan
Interests: apoptosis; autophagy; metastasis; anti-cancer; nature compound; cell biochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

More and more anti-cancer and anti-inflammatory active substances are being discovered and applied in cancer and inflammation treatment, and focus on the basic research on antiviral and antibacterial, also playing an important role in the molecular activity and biotechnology innovation of food and cosmetics.

In this Special Issue, we are collecting papers regarding the role and molecular mechanisms of active substances in anti-inflammation and anti-cancer treatment, food and cosmetics. We welcome research articles and review papers focused on anti-cancer and anti-inflammatory active substances in cancer, from basic, translational science studies to clinical research.

This Special Issue is supervised by Dr. Ming-Ju Hsieh and assisted by our Topical Advisory Panel Member Dr. Aleksandra Kalinska (Warsaw University of Life Sciences).

Dr. Ming-Ju Hsieh
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

anti-inflammatory
anti-cancer
antioxidants
antiproliferative
antiviral
antibacterial
antibodies
molecular mechanism
chemoresistance
molecular biology

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Published Papers (11 papers)

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Research

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16 pages, 6791 KiB

Open AccessArticle

Tetramethyl Cucurbit[6]uril–Porphyrin Supramolecular Polymer Enhances Photosensitization

by Bo Xiao, Yueyue Liao, Jinyu Zhang, Ke Chen, Guangwei Feng, Jian Feng and Chunlin Zhang

Int. J. Mol. Sci. 2024, 25(23), 13037; https://doi.org/10.3390/ijms252313037 - 4 Dec 2024

Viewed by 430

Abstract

Porphyrins serve as photosensitizers (PS) in the realm of cancer photodynamic therapy (PDT). Upon excitation by laser light, porphyrins are capable of converting molecular oxygen into highly cytotoxic singlet oxygen (¹O₂). However, the rigid π-conjugated structure of porphyrins frequently results in the formation of aggregates in aqueous solutions, which leads to the self-quenching of the excited state. Cucurbit[n]urils exhibit the capacity to stably bind with porphyrins via host–guest interactions, effectively inhibiting their aggregation and potentially enhancing the therapeutic efficacy of PDT. In this study, water-soluble tetramethyl cucurbit[6]uril (TMeQ[6]) was selected as the host, while four propionic acid group-appended porphyrin cationic (TPPOR) was utilized as guests to construct a supramolecular photosensitizer (TPPOR-2TMeQ[6]) in a molar ratio of 2:1. Further experimental findings demonstrate that the presence of TMeQ[6] inhibits the aggregation of TPPOR through non-covalent interactions. This inhibition reduces the energy difference between the excited singlet and triplet states, thereby enhancing the conversion efficiency of ¹O₂. Moreover, TPPOR-2TMeQ[6] exhibits favorable biocompatibility and minimal dark toxicity against breast cancer cells (4T1). Upon intracellular excitation, the levels of reactive oxygen species (ROS) significantly increase, inducing oxidative stress in 4T1 cells and leading to apoptosis. Consequently, the findings of this study suggest that the enhanced photosensitization achieved through this supramolecular approach is likely to promote the anticancer therapeutic effects of PDT, thereby broadening the application prospects of porphyrins within PDT systems. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

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23 pages, 1498 KiB

Open AccessArticle

Potential Antitumor Mechanism of Propolis Against Skin Squamous Cell Carcinoma A431 Cells Based on Untargeted Metabolomics

by Jie Wang, Liyuan Cheng, Jingjing Li, Yicong Wang, Siyuan Chen, Zhongdan Wang and Wenchao Yang

Int. J. Mol. Sci. 2024, 25(20), 11265; https://doi.org/10.3390/ijms252011265 - 19 Oct 2024

Viewed by 934

Abstract

Propolis is a sticky substance produced by honeybees (Apis mellifera) through the collection of plant resins, which they mix with secretions from their palate and wax glands. Propolis can inhibit tumor invasion and metastasis, thereby reducing the proliferation of tumor cells and inducing cell apoptosis. Previous research has shown that propolis has an inhibitory effect on skin squamous cell carcinoma A431 cells. Nevertheless, its inhibitory mechanism is unclear because of many significantly different Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the ethanol extract of the propolis (EEP) group and the control group of cells. In this study, the main components of EEP and the antitumor mechanism at an IC₅₀ of 29.04 μg/mL EEP were determined via untargeted metabolomics determined using ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC‒MS/MS), respectively. The results revealed 43 polyphenolic components in the EEP and 1052 metabolites, with 160 significantly upregulated and 143 significantly downregulated metabolites between cells treated with EEP and solvent. The KEGG enrichment results revealed that EEP significantly inhibited A431 cell proliferation via the steroid hormone biosynthesis and linoleic acid metabolism pathways. These findings may provide valuable insights for the development of targeted therapies for the treatment of cutaneous squamous cell carcinoma. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

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15 pages, 2798 KiB

Open AccessArticle

Betulonic Acid Inhibits Type-2 Porcine Reproductive and Respiratory Syndrome Virus Replication by Downregulating Cellular ATP Production

by Feixiang Long, Lizhan Su, Mingxin Zhang, Shuhua Wang, Qian Sun, Jinyi Liu, Weisan Chen, Haihong Wang and Jianxin Chen

Int. J. Mol. Sci. 2024, 25(19), 10366; https://doi.org/10.3390/ijms251910366 - 26 Sep 2024

Viewed by 712

Abstract

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRS virus (PRRSV) infection, has been a serious threat to the pork industry worldwide and continues to bring significant economic loss. Current vaccination strategies offer limited protection against PRRSV transmission, highlighting the urgent need for novel antiviral approaches. In the present study, we reported for the first time that betulonic acid (BA), a widely available pentacyclic triterpenoids throughout the plant kingdom, exhibited potent inhibition on PRRSV infections in both Marc-145 cells and primary porcine alveolar macrophages (PAMs), with IC₅₀ values ranging from 3.3 µM to 3.7 µM against three different type-2 PRRSV strains. Mechanistically, we showed that PRRSV replication relies on energy supply from cellular ATP production, and BA inhibits PRRSV infection by reducing cellular ATP production. Our findings indicate that controlling host ATP production could be a potential strategy to combat PRRSV infections, and that BA might be a promising therapeutic agent against PRRSV epidemics. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

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13 pages, 4550 KiB

Open AccessArticle

Oleuropein Relieves Pancreatic Ischemia Reperfusion Injury in Rats by Suppressing Inflammation and Oxidative Stress through HMGB1/NF-κB Pathway

by Maged S. Abdel-Kader, Rehab F. Abdel-Rahman, Gamal A. Soliman, Hanan A. Ogaly, Mohammed A. Alamri and Abdulrahman G. Alharbi

Int. J. Mol. Sci. 2024, 25(18), 10171; https://doi.org/10.3390/ijms251810171 - 22 Sep 2024

Viewed by 887

Abstract

Oleuropein (OLP) is a naturally occurring phenolic compound in olive plant with antioxidant and anti-inflammatory potential and can possibly be used in treating pancreatic injuries. This investigation aimed to follow the molecular mechanism behind the potential therapeutic effect of OLP against pancreatic injury persuaded by ischemia–reperfusion (I/R). Pancreatic I/R injury was induced by splenic artery occlusion for 60 min followed by reperfusion. Oral administration of OLP (10 and 20 mg/kg) for 2 days significantly alleviated I/R-persuaded oxidative damage and inflammatory responses in pancreatic tissue as indicated by the decreased malondialdehyde (MDA) content and increased glutathione peroxidase (GPx) activity, accompanied by the suppression of myeloperoxidase (MPO) activity and reduced levels of interleukin-1beta (IL-1β), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α) in pancreatic tissues. Furthermore, OLP treatment markedly restored the serum levels of amylase, trypsinogen-activated peptide (TAP), and lipase, with concurrent improvement in pancreatic histopathological alterations. Moreover, treatment with OLP regulated the pancreatic expression of inducible nitric oxide synthase (iNOS) and high-mobility group box 1 (HMGB1) relative to rats of the pancreatic IR group. Thus, OLP treatment significantly alleviates the I/R-induced pancreatic injury by inhibiting oxidative stress and inflammation in rats through downregulation of HMGB1 and its downstream NF-κB signaling pathway. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

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8 pages, 224 KiB

Open AccessArticle

Association of Titin Polymorphisms with the Progression of Oral Squamous Cell Carcinoma and Its Clinicopathological Characteristics

by Ching-Hui Hsu, Mu-Kuan Chen, Yu-Sheng Lo, Hsin-Yu Ho, Chia-Chieh Lin, Yi-Ching Chuang, Ming-Ju Hsieh and Ming-Chih Chou

Int. J. Mol. Sci. 2024, 25(18), 9878; https://doi.org/10.3390/ijms25189878 - 12 Sep 2024

Viewed by 1079

Abstract

This study examined the correlation of titin (TTN) polymorphisms with the sensitivity of oral squamous cell cancer (OSCC) and clinical characteristics. Six TTN SNPs, including rs10497520, rs12463674, rs12465459, rs2042996, rs2244492, and rs2303838, were evaluated in 322 control groups and 606 patients with oral cancer. We then investigated whether the SNP genotypes rs10497520 had associations with clinical pathological categories. Our data showed that the TC + CC genotype of rs10497520 was associated with moderate/poor tumor cell differentiation. The carriers of TTN rs10497520 polymorphic variant “TC + CC” in OSCC patients with cigarette smoking were linked with poor tumor differentiation (p = 0.008). Our results suggest that the TTN SNP rs10497520 is a possible genetic marker for oral cancer patients in the cigarette-smoking population. The TTN rs10497520 polymorphisms may be essential biomarkers to predict the onset and prognosis of oral cancer disease. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

12 pages, 11142 KiB

Open AccessArticle

Excellent Antibacterial Properties of Silver/Silica–Chitosan/Polyvinyl Alcohol Transparent Film

by Taoyang Cai, Shangjie Ge-Zhang, Chang Zhang, Pingxuan Mu and Jingang Cui

Int. J. Mol. Sci. 2024, 25(15), 8125; https://doi.org/10.3390/ijms25158125 - 25 Jul 2024

Viewed by 789

Abstract

Transparent films with excellent antibacterial properties and strong mechanical properties are highly sought after in packaging applications. In this study, Ag/SiO₂ nanoparticles were introduced into a mixed solution of chitosan (CS) and polyvinyl alcohol (PVA) and a Ag/SiO₂-CS-PVA transparent film was developed. The excellent properties of the film were confirmed by light transmittance, water contact angle tests and tensile tests. In addition, for the antibacterial test, the antibacterial properties of the sample against Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) were explored, and the average size of the bacteriostatic circle was measured by the cross method. The final results show that Ag/SiO₂-CS-PVA transparent film has the advantages of good antibacterial properties, high transparency and high mechanical strength. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

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14 pages, 6445 KiB

Open AccessArticle

Fangchinoline Inhibits African Swine Fever Virus Replication by Suppressing the AKT/mTOR/NF-κB Signaling Pathway in Porcine Alveolar Macrophages

by Guanming Su, Xiaoqun Yang, Qisheng Lin, Guoming Su, Jinyi Liu, Li Huang, Weisan Chen, Wenkang Wei and Jianxin Chen

Int. J. Mol. Sci. 2024, 25(13), 7178; https://doi.org/10.3390/ijms25137178 - 29 Jun 2024

Viewed by 1219

Abstract

African swine fever (ASF), caused by the African swine fever virus (ASFV), is one of the most important infectious diseases that cause high morbidity and mortality in pigs and substantial economic losses to the pork industry of affected countries due to the lack of effective vaccines. The need to develop alternative robust antiviral countermeasures, especially anti-ASFV agents, is of the utmost urgency. This study shows that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid found in the roots of Stephania tetrandra of the family Menispermaceae, significantly inhibits ASFV replication in porcine alveolar macrophages (PAMs) at micromolar concentrations (IC₅₀ = 1.66 µM). Mechanistically, the infection of ASFV triggers the AKT/mTOR/NF-κB signaling pathway. FAN significantly inhibits ASFV-induced activation of such pathways, thereby suppressing viral replication. Such a mechanism was confirmed using an AKT inhibitor MK2206 as it inhibited AKT phosphorylation and ASFV replication in PAMs. Altogether, the results suggest that the AKT/mTOR pathway could potentially serve as a treatment strategy for combating ASFV infection and that FAN could potentially emerge as an effective novel antiviral agent against ASFV infections and deserves further in vivo antiviral evaluations. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

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18 pages, 12316 KiB

Open AccessArticle

Mechanism Analysis of Antimicrobial Peptide NoPv1 Related to Potato Late Blight through a Computer-Aided Study

by Jiao-Shuai Zhou, Hong-Liang Wen and Ming-Jia Yu

Int. J. Mol. Sci. 2024, 25(10), 5312; https://doi.org/10.3390/ijms25105312 - 13 May 2024

Viewed by 962

Abstract

Phytophthora infestans (Mont.) de Bary, the oomycotic pathogen responsible for potato late blight, is the most devastating disease of potato production. The primary pesticides used to control oomycosis are phenyl amide fungicides, which cause environmental pollution and toxic residues harmful to both human and animal health. To address this, an antimicrobial peptide, NoPv1, has been screened to target Plasmopara viticola cellulose synthase 2 (PvCesA2) to inhibit the growth of Phytophthora infestans (P. infestans). In this study, we employed AlphaFold2 to predict the three-dimensional structure of PvCesA2 along with NoPv peptides. Subsequently, utilizing computational methods, we dissected the interaction mechanism between PvCesA2 and these peptides. Based on this analysis, we performed a saturation mutation of NoPv1 and successfully obtained the double mutants DP1 and DP2 with a higher affinity for PvCesA2. Meanwhile, dynamics simulations revealed that both DP1 and DP2 utilize a mechanism akin to the barrel-stave model for penetrating the cell membrane. Furthermore, the predicted results showed that the antimicrobial activity of DP1 was superior to that of NoPv1 without being toxic to human cells. These findings may offer insights for advancing the development of eco-friendly pesticides targeting various oomycete diseases, including late blight. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

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16 pages, 3290 KiB

Open AccessArticle

Synthesis, Pharmacokinetic Profile, Anticancer Activity and Toxicity of the New Amides of Betulonic Acid—In Silico and In Vitro Study

by Ewa Bębenek, Zuzanna Rzepka, Justyna Magdalena Hermanowicz, Elwira Chrobak, Arkadiusz Surażyński, Artur Beberok and Dorota Wrześniok

Int. J. Mol. Sci. 2024, 25(8), 4517; https://doi.org/10.3390/ijms25084517 - 20 Apr 2024

Cited by 2 | Viewed by 1243

Abstract

Betulonic acid (B(O)A) is a pentacyclic lupane-type triterpenoid that widely exists in plants. There are scientific reports indicating anticancer activity of B(O)A, as well as the amides and esters of this triterpenoid. In the first step of the study, the synthesis of novel amide derivatives of B(O)A containing an acetylenic moiety was developed. Subsequently, the medium-soluble compounds (EB171 and EB173) and the parent compound, i.e., B(O)A, were investigated for potential cytotoxic activity against breast cancer (MCF-7 and MDA-MB-231) and melanoma (C32, COLO 829 and A375) cell lines, as well as normal human fibroblasts. Screening analysis using the WST-1 test was applied. Moreover, the lipophilicity and ADME parameters of the obtained derivatives were determined using experimental and in silico methods. The toxicity assay using zebrafish embryos and larvae was also performed. The study showed that the compound EB171 exhibited a significant cytotoxic effect on cancer cell lines: MCF-7, A-375 and COLO 829, while it did not affect the survival of normal cells. Moreover, studies on embryos and larvae showed no toxicity of EB171 in an animal model. Compared to EB171, the compound EB173 had a weaker effect on all tested cancer cell lines and produced less desirable effects against normal cells. The results of the WST-1 assay obtained for B(O)A revealed its strong cytotoxic activity on the examined cancer cell lines, but also on normal cells. In conclusion, this article describes new derivatives of betulonic acid—from synthesis to biological properties. The results allowed to indicate a promising direction for the functionalization of B(O)A to obtain derivatives with selective anticancer activity and low toxicity. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

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26 pages, 4121 KiB

Open AccessArticle

Study on the Anti-Ulcerative Colitis Effect of Pseudo-Ginsenoside RT4 Based on Gut Microbiota, Pharmacokinetics, and Tissue Distribution

by Hui Yu, Caixia Wang, Junzhe Wu, Qianyun Wang, Hanlin Liu, Zhuoqiao Li, Shanmei He, Cuizhu Wang and Jinping Liu

Int. J. Mol. Sci. 2024, 25(2), 835; https://doi.org/10.3390/ijms25020835 - 9 Jan 2024

Viewed by 1685

Abstract

The purpose of this study was to explore the therapeutic effect of the oral administration of pseudo-ginsenoside RT4 (RT4) on ulcerative colitis (UC), and to determine the rate of absorption and distribution of RT4 in mice with UC. Balb/c mice were induced using dextran sulfate sodium salts (DSS) to establish the UC model, and 10, 20, or 40 mg/kg of RT4 was subsequently administered via gavage. The clinical symptoms, inflammatory response, intestinal barrier, content of total short-chain fatty acids (SCFAs), and gut microbiota were investigated. Caco-2 cells were induced to establish the epithelial barrier damage model using LPS, and an intervention was performed using 4, 8, and 16 µg/mL of RT4. The inflammatory factors, transient electrical resistance (TEER), and tight-junction protein expression were determined. Finally, pharmacokinetic and tissue distribution studies following the intragastric administration of RT4 in UC mice were performed. According to the results in mice, RT4 decreased the disease activity index (DAI) score, restored the colon length, reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and boosted the levels of immunosuppressive cytokine IL-10, increased the content of SCFAs, improved the colonic histopathology, maintained the ultrastructure of colonic mucosal epithelial cells, and corrected disturbances in the intestinal microbiota. Based on the results in caco-2 cells, RT4 reduced the levels of TNF-α, IL-6, and IL-1β; protected integrity of monolayers; and increased tight-junction protein expression. Additionally, the main pharmacokinetic parameters (C_max, T_max, t_1/2, V_d, CL, AUC) were obtained, the absolute bioavailability was calculated as 18.90% ± 2.70%, and the main distribution tissues were the small intestine and colon. In conclusion, RT4, with the features of slow elimination and directional distribution, could alleviate UC by inhibiting inflammatory factors, repairing the intestinal mucosal barrier, boosting the dominant intestinal microflora, and modulating the expression of SCFAs. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

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Review

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16 pages, 770 KiB

Open AccessReview

Perspectives and Possibilities for New Antimicrobial Agents in the Treatment and Control of Mastitis Induced by Algae of the Genus Prototheca spp.: A Review

by Weronika Jabłońska, Marcin Gołębiewski, Magdalena Kot, Henadzi Mardan, Bartosz Pawliński and Aleksandra Kalińska

Int. J. Mol. Sci. 2024, 25(15), 8219; https://doi.org/10.3390/ijms25158219 - 27 Jul 2024

Viewed by 1469

Abstract

Innovative approaches in nanotechnology provide a potentially promising alternative to untreatable cases of mastitis caused by genus Prototheca spp. algae infections. Drying of the teats of the affected animals or culling are typically the outcomes of mastitis in dairy cattle caused by these pathogens. A major issue in both veterinary medicine and animal breeding is the Prototheca species’ widespread resistance to the current methods of managing infections and the available drugs, including antibiotics. Commercial antifungal preparations are also ineffective. Nanotechnology, an emerging discipline, has the potential to create an effective alternative treatment for protothecal mastitis. The aim of the paper is to combine the literature data on the use of nanotechnology in the control of mastitis, taking into account data on combating mastitis caused by Prototheca spp. infections. The databases employed were PubMed, Google Scholar, and Scopus, focusing on literature from the last 20 years to ensure relevance and currency. Studies conducted in vitro have demonstrated that nanomaterials have significant biocidal activity against mastitis infections of different etiologies. Analyzed research papers show that (NPs), such as AgNPs, CuNPs, AuNPs, etc., may not negatively impact various cell lines and may be effective agents in reducing the pathogens’ viability. However, it is also critical to assess the risks involved in using nanomaterials. Full article

(This article belongs to the Special Issue Anti-Cancer, Anti-Inflammatory, and Antioxidation Active Substances: 2nd Edition)

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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Planned Paper I: Griffithazanone A promotes apoptosis and reverses Osimertinib resistant in NSCLC by targeting PIM1- Dr. Xiao(Submission date To be determined)

Planned Paper II: Picrasidine I induced apoptosis by triggering claspin in melanoma cells- Professor. Ming-Ju Hsieh(Submission date To be determined)

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