Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antioxidants antioxidants	6.0	10.6	2012	16.9 Days	CHF 2900
Biomolecules biomolecules	4.8	9.4	2011	18.4 Days	CHF 2700
Cancers cancers	4.5	8.0	2009	17.4 Days	CHF 2900
Cells cells	5.1	9.9	2012	17 Days	CHF 2700
International Journal of Molecular Sciences ijms	4.9	8.1	2000	16.8 Days	CHF 2900
Pathogens pathogens	3.3	6.4	2012	15.3 Days	CHF 2200

17 pages, 2975 KiB

Open AccessArticle

Artesunate Inhibits Metastatic Potential in Cisplatin-Resistant Bladder Cancer Cells by Altering Integrins

by Olesya Vakhrusheva, Fuguang Zhao, Sascha Dennis Markowitsch, Kimberly Sue Slade, Maximilian Peter Brandt, Igor Tsaur, Jindrich Cinatl, Jr., Martin Michaelis, Thomas Efferth, Roman Alexander Blaheta, Axel Haferkamp and Eva Juengel

Cells 2025, 14(8), 570; https://doi.org/10.3390/cells14080570 - 10 Apr 2025

Viewed by 278

Abstract

The survival of patients with locally advanced and metastatic bladder cancer (BCa) is persistently low. Hence, new treatment options are urgently needed. Artesunate (ART) a derivative of artemisinin, used in Traditional Chinese Medicine, shows anti-tumor activity extending over a broad spectrum of human [...] Read more.

The survival of patients with locally advanced and metastatic bladder cancer (BCa) is persistently low. Hence, new treatment options are urgently needed. Artesunate (ART) a derivative of artemisinin, used in Traditional Chinese Medicine, shows anti-tumor activity extending over a broad spectrum of human cancers. As we have previously shown, ART inhibits growth in cisplatin-sensitive (parental) and cisplatin-resistant BCa cells. However, how ART acts on the metastatic potential of BCa remained unclear. To clarify, we applied ART to parental and cisplatin-resistant RT4, RT112, T24, and TCCSup BCa cell lines. We examined tumor cell adhesion to vascular endothelium and immobilized collagen and evaluated chemotactic activity, migration, and invasive activity of the BCa cells. Adhesion receptors, integrin α and β subtypes, integrin-linked kinase (ILK), and focal adhesion kinase (FAK) were investigated. The functional relevance of integrin expression altered by ART was determined by blocking studies. ART significantly reduced tumor cell adhesion to vascular endothelium and immobilized collagen in parental as well as in cisplatin-resistant BCa cells. Depending on cell type, ART suppressed tumor cell motility and diminished integrin expression (surface and total). Functional blocking of integrins altered by ART reduced cell adhesion and invasion of the BCa cells. Thus, the metastatic potential of parental and cisplatin-resistant BCa cells was significantly inhibited by ART, making it a promising treatment option for patients with advanced or therapy-resistant BCa. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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24 pages, 2490 KiB

Open AccessReview

Therapeutic Potential of Prunus Species in Gastrointestinal Oncology

by Gabriela Mitea, Irina Mihaela Iancu, Verginica Schröder, Adrian Cosmin Roșca, Valeriu Iancu, Ruxandra-Mihaela Crețu and Horațiu Mireșan

Cancers 2025, 17(6), 938; https://doi.org/10.3390/cancers17060938 - 10 Mar 2025

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Abstract

Background: Gastrointestinal tract cancers represent a significant worldwide health concern, accounting for almost one-third of cancer-related deaths. The existing chemotherapy drugs used in gastrointestinal cancers are ineffective, so prognosis is poor, recurrence and metastasis rates are high, and survival time remains short, necessitating [...] Read more.

Background: Gastrointestinal tract cancers represent a significant worldwide health concern, accounting for almost one-third of cancer-related deaths. The existing chemotherapy drugs used in gastrointestinal cancers are ineffective, so prognosis is poor, recurrence and metastasis rates are high, and survival time remains short, necessitating the development of novel antitumor drugs that exhibit low toxicity and less potential for the development of drug resistance. This challenge is considerable, but evidence from the past decades supports the medicinal properties and functionalities of bioactive compounds such as flavonoids and acid phenolics with anticancer activities. Our purpose was to find data on the relationship between gastrointestinal cancer and bioactive compounds from Prunus species, focusing on their molecular mechanisms of action. Results: Studies highlight the potential of bioactive compounds from Prunus species to modulate the cancer cell signaling pathways involved in gastrointestinal tumorigenesis. Conclusions: The studies reviewed suggest that polyphenols from Prunus species exhibit promising gastrointestinal anticancer activities and could represent an adjunctive therapeutic strategy in cancer treatment. Further studies are necessary to validate these compounds’ therapeutic potential and their feasibility as cost-effective treatments for cancer. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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15 pages, 1434 KiB

Open AccessArticle

Lithocholic Acid’s Ionic Compounds as Promising Antitumor Agents: Synthesis and Evaluation of the Production of Reactive Oxygen Species (ROS) in Mitochondria

by Nuri M. Chobanov, Lilya U. Dzhemileva, Usein M. Dzhemilev and Vladimir A. D’yakonov

Antioxidants 2024, 13(12), 1448; https://doi.org/10.3390/antiox13121448 - 25 Nov 2024

Cited by 1 | Viewed by 998

Abstract

The development of a methodology for the synthesis of new compounds with antitumor activity represents a significant and priority task within the field of medicinal chemistry. As a continuation of our research group’s earlier studies on the antitumor activity of ionic derivatives of [...] Read more.

The development of a methodology for the synthesis of new compounds with antitumor activity represents a significant and priority task within the field of medicinal chemistry. As a continuation of our research group’s earlier studies on the antitumor activity of ionic derivatives of natural compounds, we have synthesized a series of previously undescribed pyrazole ionic compounds through a series of transformations of lithocholic acid methyl ester. To investigate the biological activity of the newly synthesized lithocholic acid derivatives, a series of modern flow cytometry techniques were employed to assess their cytotoxic activity, effects on the cell cycle, and induction of apoptosis. This included the analysis of alterations in the mitochondrial potential, accumulation of ROS ions in mitochondria, and loss of cytochrome c. These compounds demonstrate promising antitumor activity through their effects on mitochondrial oxidation and phosphorylation processes. These compounds, which we have designated as “soft dissociators”, exhibit enhanced biopharmacological properties relative to the original lithocholic acid molecule. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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15 pages, 2080 KiB

Open AccessArticle

New Synthetic Analogs of Natural 5Z,9Z-Dienoic Acids—Hybrid Molecules Based on Oleanolic Acid: Synthesis and Study of Antitumor Activity

by Regina A. Tuktarova, Lilya U. Dzhemileva, Usein M. Dzhemilev and Vladimir A. D’yakonov

Cancers 2024, 16(23), 3893; https://doi.org/10.3390/cancers16233893 - 21 Nov 2024

Viewed by 712

Abstract

Objectives: A series of synthetic analogs of natural (5Z,9Z)-diene acids were synthesized for the first time in the form of hybrid molecules containing an oleanolic acid fragment. This fragment was simultaneously linked by an amide bond to various hetero- and carbocyclic amines [...] Read more.

Objectives: A series of synthetic analogs of natural (5Z,9Z)-diene acids were synthesized for the first time in the form of hybrid molecules containing an oleanolic acid fragment. This fragment was simultaneously linked by an amide bond to various hetero- and carbocyclic amines and a complex ester bond to (5Z,9Z)-tetradeca-5,9-dienecarboxylic acid, which was synthesized by a new reaction of Ti-catalyzed homocyclomagnification of 1,2-dienes. Results: Among the synthesized hybrids, the highest cytotoxic activity was observed for compound 9a in the series of Jurkat, K562, U937, and HEK293, with IC50 values of 4.5; 3.1; 2.8; and 26.17 μM/L, respectively. Furthermore, the synthesized compound 9a has been observed to induce apoptosis and exhibit genotoxicity in Jurkat culture, which suggests that it may be a promising candidate for further investigation as an antitumor agent. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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19 pages, 1205 KiB

Open AccessArticle

Chemical and Biological Characterization of Metabolites from Silene viridiflora Using Mass Spectrometric and Cell-Based Assays

by Nilufar Z. Mamadalieva, Alexey Koval, Maksud M. Dusmuratov, Hidayat Hussain and Vladimir L. Katanaev

Biomolecules 2024, 14(10), 1285; https://doi.org/10.3390/biom14101285 - 11 Oct 2024

Viewed by 1339

Abstract

A comprehensive metabolite profiling of the medicinal plant Silene viridiflora using an UHPLC-ESI-MS/MS method is described for the first time. A total of 71 compounds were identified and annotated, the most common of which were flavonoids, triterpene glycosides, and ecdysteroids. The three major [...] Read more.

A comprehensive metabolite profiling of the medicinal plant Silene viridiflora using an UHPLC-ESI-MS/MS method is described for the first time. A total of 71 compounds were identified and annotated, the most common of which were flavonoids, triterpene glycosides, and ecdysteroids. The three major compounds schaftoside, 26-hydroxyecdysone, and silviridoside can be chosen as the markers for the assessment of the quality of S. viridiflora preparations. The methanol extract and a variety of metabolites identified in S. viridiflora were screened for their cytotoxic and Wnt pathway-inhibiting activities against triple-negative breast cancer (TNBC), the deadliest form of cancer in women. 2-Deoxy-20-hydroxyecdysone with submicromolar IC₅₀ was identified as a result. The structure–activity relationship derived from the data from the in vitro proliferation assay showed that the hydroxyl group present at position C-2 of steroid core reduces the ecdysteroids’ cytotoxicity against cancer cells. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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19 pages, 3791 KiB

Open AccessEditor’s ChoiceArticle

Synergistic Inhibition of Pancreatic Cancer Cell Growth and Migration by Gemcitabine and Withaferin A

by Renata Szydlak

Biomolecules 2024, 14(9), 1178; https://doi.org/10.3390/biom14091178 - 19 Sep 2024

Viewed by 1429

Abstract

Pancreatic cancer remains one of the most lethal malignancies due to its aggressive nature and resistance to conventional therapies. This study investigates the anti-proliferative, pro-apoptotic, and anti-migratory effects of Gemcitabine (GC) and Withaferin A (WFA) on pancreatic cancer cell lines PANC-1 and Hs766t. [...] Read more.

Pancreatic cancer remains one of the most lethal malignancies due to its aggressive nature and resistance to conventional therapies. This study investigates the anti-proliferative, pro-apoptotic, and anti-migratory effects of Gemcitabine (GC) and Withaferin A (WFA) on pancreatic cancer cell lines PANC-1 and Hs766t. The MTS assay revealed that both compounds effectively inhibit cell proliferation, with WFA showing a stronger effect in Hs766t cells. Flow cytometry analysis demonstrated that GC and WFA, particularly in combination, significantly induce apoptosis in both cell lines. Migration assays confirmed the potent inhibition of cell migration by both compounds, with the combination treatment being the most effective. Furthermore, actin cytoskeleton analysis indicated substantial changes in cell morphology and stiffness, suggesting that GC and WFA disrupt the structural integrity of cancer cells. Additionally, the study highlights a ROS-mediated mechanism underlying the effects of GC and WFA, as evidenced by increased ROS levels following treatment, which were attenuated by N-acetylcysteine. Importantly, NF-κB activity was significantly modulated, with WFA reducing NF-κB activation induced by GC, potentially contributing to the synergistic pro-apoptotic effect of the combination. These findings suggest that the combination of GC and WFA may offer a synergistic therapeutic approach for treating pancreatic cancer by targeting multiple aspects of tumor cell behavior. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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27 pages, 14865 KiB

Open AccessArticle

Lumbrokinase Extracted from Earthworms Synergizes with Bevacizumab and Chemotherapeutics in Treating Non-Small Cell Lung Cancer by Targeted Inactivation of BPTF/VEGF and NF-κB/COX-2 Signaling

by Chunyu Hua, Ziyue Guo, Meng Dai, Jie Zhou, Hanxiao Ge, Guoqing Xue, Fahui Xu, Liyuan Ru, Kuan Lv, Guohui Zhang, Lina Zheng, Meiyi Wang, Yun Teng, Wendan Yu and Wei Guo

Biomolecules 2024, 14(7), 741; https://doi.org/10.3390/biom14070741 - 23 Jun 2024

Cited by 1 | Viewed by 2659

Abstract

As a kind of proteolytic enzyme extracted from earthworms, lumbrokinase has been used as an antithrombotic drug clinically. Nevertheless, its potential in anti-cancer, especially in anti-non-small cell lung cancer (NSCLC), as a single form of treatment or in combination with other therapies, [...] Read more.

As a kind of proteolytic enzyme extracted from earthworms, lumbrokinase has been used as an antithrombotic drug clinically. Nevertheless, its potential in anti-cancer, especially in anti-non-small cell lung cancer (NSCLC), as a single form of treatment or in combination with other therapies, is still poorly understood. In this study, we explored the anti-tumor role and the responsive molecular mechanisms of lumbrokinase in suppressing tumor angiogenesis and chemoresistance development in NSCLC and its clinical potential in combination with bevacizumab and chemotherapeutics. Lumbrokinase was found to inhibit cell proliferation in a concentration-dependent manner and caused metastasis suppression and apoptosis induction to varying degrees in NSCLC cells. Lumbrokinase enhanced the anti-angiogenesis efficiency of bevacizumab by down-regulating BPTF expression, decreasing its anchoring at the VEGF promoter region and subsequent VEGF expression and secretion. Furthermore, lumbrokinase treatment reduced IC50 values of chemotherapeutics and improved their cytotoxicity in parental and chemo-resistant NSCLC cells via inactivating the NF-κB pathway, inhibiting the expression of COX-2 and subsequent secretion of PGE2. LPS-induced NF-κB activation reversed its inhibition on NSCLC cell proliferation and its synergy with chemotherapeutic cytotoxicity, while COX-2 inhibitor celecoxib treatment boosted such effects. Lumbrokinase combined with bevacizumab, paclitaxel, or vincristine inhibited the xenograft growth of NSCLC cells in mice more significantly than a single treatment. In conclusion, lumbrokinase inhibited NSCLC survival and sensitized NSCLC cells to bevacizumab or chemotherapeutics treatment by targeted down-regulation of BPTF/VEGF signaling and inactivation of NF-κB/COX-2 signaling, respectively. The combinational applications of lumbrokinase with bevacizumab or chemotherapeutics are expected to be developed as promising candidate therapeutic strategies to improve the efficacy of the original monotherapy in anti-NSCLC. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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20 pages, 1525 KiB

Open AccessReview

Research on the Medicinal Chemistry and Pharmacology of Taxus × media

by Xinyu Gao, Ni Zhang and Weidong Xie

Int. J. Mol. Sci. 2024, 25(11), 5756; https://doi.org/10.3390/ijms25115756 - 25 May 2024

Cited by 2 | Viewed by 1640

Abstract

Taxus × media, belonging to the genus Taxus of the Taxaceae family, is a unique hybrid plant derived from a natural crossbreeding between Taxus cuspidata and Taxus baccata. This distinctive hybrid variety inherits the superior traits of its parental species, exhibiting [...] Read more.

Taxus × media, belonging to the genus Taxus of the Taxaceae family, is a unique hybrid plant derived from a natural crossbreeding between Taxus cuspidata and Taxus baccata. This distinctive hybrid variety inherits the superior traits of its parental species, exhibiting significant biological and medicinal values. This paper comprehensively analyzes Taxus × media from multiple dimensions, including its cultivation overview, chemical composition, and multifaceted applications in the medical field. In terms of chemical constituents, this study delves into the bioactive components abundant in Taxus × media and their pharmacological activities, highlighting the importance and value of these components, including paclitaxel, as the lead compounds in traditional medicine and modern drug development. Regarding its medicinal value, the article primarily discusses the potential applications of Taxus × media in combating tumors, antibacterial, anti-inflammatory, and antioxidant activities, and treating diabetes. By synthesizing clinical research and experimental data, the paper elucidates the potential and mechanisms of its primary active components in preventing and treating these diseases. In conclusion, Taxus × media demonstrates its unique value in biological research and tremendous potential in drug development. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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18 pages, 1967 KiB

Open AccessReview

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers

by Xiaochang Shen, Jiandong Wang, Boer Deng, Ziyi Zhao, Shuning Chen, Weimin Kong, Chunxiao Zhou and Victoria Bae-Jump

Antioxidants 2024, 13(5), 617; https://doi.org/10.3390/antiox13050617 - 19 May 2024

Cited by 4 | Viewed by 2471

Abstract

Ascorbate (vitamin C) is an essential vitamin for the human body and participates in various physiological processes as an important coenzyme and antioxidant. Furthermore, the role of ascorbate in the prevention and treatment of cancer including gynecological cancer has gained much more interest [...] Read more.

Ascorbate (vitamin C) is an essential vitamin for the human body and participates in various physiological processes as an important coenzyme and antioxidant. Furthermore, the role of ascorbate in the prevention and treatment of cancer including gynecological cancer has gained much more interest recently. The bioavailability and certain biological functions of ascorbate are distinct in males versus females due to differences in lean body mass, sex hormones, and lifestyle factors. Despite epidemiological evidence that ascorbate-rich foods and ascorbate plasma concentrations are inversely related to cancer risk, ascorbate has not demonstrated a significant protective effect in patients with gynecological cancers. Adequate ascorbate intake may have the potential to reduce the risk of human papillomavirus (HPV) infection and high-risk HPV persistence status. High-dose ascorbate exerts antitumor activity and synergizes with chemotherapeutic agents in preclinical cancer models of gynecological cancer. In this review, we provide evidence for the biological activity of ascorbate in females and discuss the potential role of ascorbate in the prevention and treatment of ovarian, endometrial, and cervical cancers. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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20 pages, 3263 KiB

Open AccessArticle

Defining a Water-Soluble Formulation of Arachidonic Acid as a Novel Ferroptosis Inducer in Cancer Cells

by Zoe I. Day, Alyce J. Mayfosh, Amy A. Baxter, Scott A. Williams, Joanne M. Hildebrand, Thomas F. Rau, Ivan K. H. Poon and Mark D. Hulett

Biomolecules 2024, 14(5), 555; https://doi.org/10.3390/biom14050555 - 4 May 2024

Cited by 1 | Viewed by 2426

Abstract

Here, we describe GS-9, a novel water-soluble fatty acid-based formulation comprising L-lysine and arachidonic acid, that we have shown to induce ferroptosis. GS-9 forms vesicle-like structures in solution and mediates lipid peroxidation, as evidenced by increased C11-BODIPY fluorescence and an accumulation of toxic [...] Read more.

Here, we describe GS-9, a novel water-soluble fatty acid-based formulation comprising L-lysine and arachidonic acid, that we have shown to induce ferroptosis. GS-9 forms vesicle-like structures in solution and mediates lipid peroxidation, as evidenced by increased C11-BODIPY fluorescence and an accumulation of toxic malondialdehyde, a downstream product of lipid peroxidation. Ferroptosis inhibitors counteracted GS-9-induced cell death, whereas caspase 3 and 7 or MLKL knock-out cell lines are resistant to GS-9-induced cell death, eliminating other cell death processes such as apoptosis and necroptosis as the mechanism of action of GS-9. We also demonstrate that through their role of sequestering fatty acids, lipid droplets play a protective role against GS-9-induced ferroptosis, as inhibition of lipid droplet biogenesis enhanced GS-9 cytotoxicity. In addition, Fatty Acid Transport Protein 2 was implicated in GS-9 uptake. Overall, this study identifies and characterises the mechanism of GS-9 as a ferroptosis inducer. This formulation of arachidonic acid offers a novel tool for investigating and manipulating ferroptosis in various cellular and anti-cancer contexts. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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15 pages, 4247 KiB

Open AccessArticle

In Vitro and In Vivo Imaging-Based Evaluation of Doxorubicin Anticancer Treatment in Combination with the Herbal Medicine Black Cohosh

by Agata Płoska, Marcin Wozniak, Jamila Hedhli, Christian J. Konopka, Antonios Skondras, Sarah Matatov, Andrew Stawarz, Sarah Schuh, Andrzej Czerwinski, Lawrence W. Dobrucki, Leszek Kalinowski and Iwona T. Dobrucki

Int. J. Mol. Sci. 2023, 24(24), 17506; https://doi.org/10.3390/ijms242417506 - 15 Dec 2023

Cited by 1 | Viewed by 1799

Abstract

As a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts [...] Read more.

As a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism. The number of apoptotic cells after incubation with both DOX and BC was significantly increased (~100%) compared to the control. Treatment with DOX altered the potential of MCF-7 cells to form colonies; however, coincubation with BC did not affect this process. In vivo, PET-CT imaging showed that combined treatment of DOX and BC induced a significant reduction in both metabolic activity (29%) and angiogenesis (32%). Both DOX and BC treatments inhibited tumor growth by 20% and 12%, respectively, and combined by 57%, vs. control. We successfully demonstrated that BC increases cytotoxic effects of DOX, resulting in a significant reduction in tumor size. Further studies regarding drug transport and tumor growth biomarkers are necessary to establish the underlying mechanism and potential clinical use of BC in breast cancer patients. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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14 pages, 3471 KiB

Open AccessArticle

Hypericin-Based Photodynamic Therapy Displays Higher Selectivity and Phototoxicity towards Melanoma and Squamous Cell Cancer Compared to Normal Keratinocytes In Vitro

by Marta Woźniak and Martyna Nowak-Perlak

Int. J. Mol. Sci. 2023, 24(23), 16897; https://doi.org/10.3390/ijms242316897 - 29 Nov 2023

Cited by 11 | Viewed by 1867

Abstract

The aim of this study was to explore the potential of hypericin, a naturally occurring photosensi-tizer, for photodynamic therapy (PDT) in skin cancer, investigating its phototoxic effects and mechanisms of action in cancer cells compared to normal skin keratinocytes, squamous cell cancer (SCC-25) [...] Read more.

The aim of this study was to explore the potential of hypericin, a naturally occurring photosensi-tizer, for photodynamic therapy (PDT) in skin cancer, investigating its phototoxic effects and mechanisms of action in cancer cells compared to normal skin keratinocytes, squamous cell cancer (SCC-25) cells and melanoma (MUG-Mel2) cells. Hypericin was applied at concentrations ranging from 0.1–40 μM to HaCaT, SCC-25, and MUG-Mel2 cells. After 24 h of incubation, the cells were exposed to orange light at 3.6 J/cm² or 7.2 J/cm². Phototoxicity was assessed using MTT and SRB tests. Cellular uptake was measured by flow cytometry. Apoptosis-positive cells were estimated through TUNEL for apoptotic bodies’ visualization. Hypericin exhibited a higher phototoxic reaction in cancer cells compared to normal keratinocytes after irradiation. Cancer cells demonstrated increased and selective uptake of hypericin. Apoptosis was observed in SCC-25 and MUG-Mel2 cells following PDT. Our findings suggest that hypericin-based PDT is a promising and less invasive approach for treating skin cancer. The higher phototoxic reaction, selective uptake by cancer cells, and observed proapoptotic properties support the promising role of hypericin-based PDT in skin cancer treatment. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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18 pages, 4537 KiB

Open AccessArticle

Pllans−II: Unveiling the Action Mechanism of a Promising Chemotherapeutic Agent Targeting Cervical Cancer Cell Adhesion and Survival Pathways

by Alejandro Montoya-Gómez, Fiorella Tonello, Barbara Spolaore, Maria Lina Massimino, Leonel Montealegre-Sánchez, Andrés Castillo, Nelson Rivera Franco, María José Sevilla-Sánchez, Luis Manuel Solano-Redondo, Mildrey Mosquera-Escudero and Eliécer Jiménez-Charris

Cells 2023, 12(23), 2715; https://doi.org/10.3390/cells12232715 - 27 Nov 2023

Cited by 1 | Viewed by 1653

Abstract

Despite advances in chemotherapeutic drugs used against cervical cancer, available chemotherapy treatments adversely affect the patient’s quality of life. For this reason, new molecules from natural sources with antitumor potential and few side effects are required. In previous research, Pllans−II, a phospholipase [...] Read more.

Despite advances in chemotherapeutic drugs used against cervical cancer, available chemotherapy treatments adversely affect the patient’s quality of life. For this reason, new molecules from natural sources with antitumor potential and few side effects are required. In previous research, Pllans−II, a phospholipase A₂ type-Asp49 from Porthidium lansbergii lansbergii snake venom, has shown selective attack against the HeLa and Ca Ski cervical cancer cell lines. This work suggests that the cytotoxic effect generated by Pllans−II on HeLa cells is triggered without affecting the integrity of the cytoplasmic membrane or depolarizing the mitochondrial membranes. The results allow us to establish that cell death in HeLa is related to the junction blockage between α₅β₁ integrins and fibronectin of the extracellular matrix. Pllans−II reduces the cells’ ability of adhesion and affects survival and proliferation pathways mediated by intracellular communication with the external environment. Our findings confirmed Pllans−II as a potential prototype for developing a selective chemotherapeutic drug against cervical cancer. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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12 pages, 2465 KiB

Open AccessArticle

New Copper-Based Metallodrugs with Anti-Invasive Capacity

by Alessia Garufi, Francesca Scarpelli, Loredana Ricciardi, Iolinda Aiello, Gabriella D’Orazi and Alessandra Crispini

Biomolecules 2023, 13(10), 1489; https://doi.org/10.3390/biom13101489 - 7 Oct 2023

Cited by 1 | Viewed by 2258

Abstract

While metal-based complexes are deeply investigated as anticancer chemotherapeutic drugs, fewer studies are devoted to their anti-invasive activity. Herein, two copper (Cu)(II) tropolone derivatives, [Cu(Trop)Cl] and [Cu(Trop)Sac], both containing the N,N-chelated 4,4′-bishydroxymethyl-2,2′-bipyridne ligand, were evaluated for their anticancer and anti-invasive properties. RKO (RKO-ctr) [...] Read more.

While metal-based complexes are deeply investigated as anticancer chemotherapeutic drugs, fewer studies are devoted to their anti-invasive activity. Herein, two copper (Cu)(II) tropolone derivatives, [Cu(Trop)Cl] and [Cu(Trop)Sac], both containing the N,N-chelated 4,4′-bishydroxymethyl-2,2′-bipyridne ligand, were evaluated for their anticancer and anti-invasive properties. RKO (RKO-ctr) colon cancer cells and their derivatives undergoing stable small interference (si) RNA for HIPK2 protein (RKO-siHIPK2) with acquisition of pro-invasive capacity were used. The results demonstrate that while [Cu(Trop)Sac] did not show cytotoxic activity, [Cu(Trop)Cl] induced cell death in both RKO-ctr and RKO-siHIPK2 cells, indicating that structural changes on substituting the coordinated chloride ligand with saccharine (Sac) could be a key factor in suppressing mechanisms of cellular death. On the other hand, both [Cu(Trop)Sac] and [Cu(Trop)Cl] complexes counteracted RKO-siHIPK2 cell migration in the wound healing assay. The synergic effect exerted by the concomitant presence of both tropolone and saccharin ligands in [Cu(Trop)Sac] was also supported by its significant inhibition of RKO-siHIPK2 cell migration compared to the free Sac ligand. These data suggest that the two Cu(II) tropolone derivatives are also interesting candidates to be further tested in in vivo models as an anti-invasive tumor strategy. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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36 pages, 4927 KiB

Open AccessReview

Potential Role of Natural Antioxidant Products in Oncological Diseases

by Pasquale Marino, Giacomo Pepe, Manuela Giovanna Basilicata, Vincenzo Vestuto, Stefania Marzocco, Giuseppina Autore, Alfredo Procino, Isabel Maria Gomez-Monterrey, Michele Manfra and Pietro Campiglia

Antioxidants 2023, 12(3), 704; https://doi.org/10.3390/antiox12030704 - 12 Mar 2023

Cited by 47 | Viewed by 5631

Abstract

Nutrition has a significant effect and a crucial role in disease prevention. Low consumption of fruit and vegetables and a sedentary lifestyle are closely related with the onset and development of many types of cancer. Recently, nutraceuticals have gained much attention in cancer [...] Read more.

Nutrition has a significant effect and a crucial role in disease prevention. Low consumption of fruit and vegetables and a sedentary lifestyle are closely related with the onset and development of many types of cancer. Recently, nutraceuticals have gained much attention in cancer research due to their pleiotropic effects and relatively non-toxic behavior. In fact, although in the past there have been conflicting results on the role of some antioxidant compounds as allies against cancer, numerous recent clinical studies highlight the efficacy of dietary phytochemicals in the prevention and treatment of cancer. However, further investigation is necessary to gain a deeper understanding of the potential anticancer capacities of dietary phytochemicals as well as the mechanisms of their action. Therefore, this review examined the current literature on the key properties of the bioactive components present in the diet, such as carotenoids, polyphenols, and antioxidant compounds, as well as their use in cancer therapy. The review focused on potential chemopreventive properties, evaluating their synergistic effects with anticancer drugs and, consequently, the side effects associated with current cancer treatments. Full article

(This article belongs to the Topic Advances in Natural Products and Phytochemicals in Cancer Prevention and Therapeutics)

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