Investigation of possible effects of apigenin, sorafenib and combined applications on apoptosis and cell cycle in hepatocellular cancer cells

Şirin, Nazlı; Elmas, Levent; Seçme, Mücahit; Dodurga, Yavuz

doi:10.1016/j.gene.2020.144428

Cited by 24 publications

(11 citation statements)

References 36 publications

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“…When combined with the chemotherapeutic sorafenib, apigenin decreased cell viability of liver cancer cells to a greater extent than either drug alone. This combination caused an increase in apoptosis and decreased the migration and invasion capability of the cells [364].…”

Section: Apigeninmentioning

confidence: 99%

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Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Tomko

Whynot

Ellis

et al. 2020

Cancers

120

109

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In recent years, and even more since its legalization in several jurisdictions, cannabis and the endocannabinoid system have received an increasing amount of interest related to their potential exploitation in clinical settings. Cannabinoids have been suggested and shown to be effective in the treatment of various conditions. In cancer, the endocannabinoid system is altered in numerous types of tumours and can relate to cancer prognosis and disease outcome. Additionally, cannabinoids display anticancer effects in several models by suppressing the proliferation, migration and/or invasion of cancer cells, as well as tumour angiogenesis. However, the therapeutic use of cannabinoids is currently limited to the treatment of symptoms and pain associated with chemotherapy, while their potential use as cytotoxic drugs in chemotherapy still requires validation in patients. Along with cannabinoids, cannabis contains several other compounds that have also been shown to exert anti-tumorigenic actions. The potential anti-cancer effects of cannabinoids, terpenes and flavonoids, present in cannabis, are explored in this literature review.

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Section: Apigeninmentioning

confidence: 99%

“…Enhanced activity of paclitaxel [362]. Apigenin + Sorafenib increased apoptosis and decreased migration and invasion [364]. Apigenin + Abivertinib had synergistic anti-cancer effects [360].…”

Section: Apigeninmentioning

confidence: 99%

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Tomko

Whynot

Ellis

et al. 2020

Cancers

120

109

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“…In increasing DOX cytotoxicity, APG inhibits DNA repair of breast cancer cells [184]. Furthermore, co-administration of APG with other anti-tumor agents such as sorafenib increases its efficacy in triggering apoptosis and cell cycle arrest in cancer cells [185]. In DOX-resistant hepatocellular carcinoma cells, APG enhances expression of miRNA-101 as a tumor-suppressing factor.…”

Section: Nrf2 In Doxorubicin Resistancementioning

confidence: 99%

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

et al. 2021

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Doxorubicin (DOX) is extensively applied in cancer therapy due to its efficacy in suppressing cancer progression and inducing apoptosis. After its discovery, this chemotherapeutic agent has been frequently used for cancer therapy, leading to chemoresistance. Due to dose-dependent toxicity, high concentrations of DOX cannot be administered to cancer patients. Therefore, experiments have been directed towards revealing underlying mechanisms responsible for DOX resistance and ameliorating its adverse effects. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is activated to increase levels of reactive oxygen species (ROS) in cells to protect them against oxidative stress. It has been reported that Nrf2 activation is associated with drug resistance. In cells exposed to DOX, stimulation of Nrf2 signaling protects cells against cell death. Various upstream mediators regulate Nrf2 in DOX resistance. Strategies, both pharmacological and genetic interventions, have been applied for reversing DOX resistance. However, Nrf2 induction is of importance for alleviating side effects of DOX. Pharmacological agents with naturally occurring compounds as the most common have been used for inducing Nrf2 signaling in DOX amelioration. Furthermore, signaling networks in which Nrf2 is a key player for protection against DOX adverse effects have been revealed and are discussed in the current review.

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“…Furthermore, the combination therapy including apigenin plus sorafenib was associated with escalation in the percentage of apoptotic cells, reduction in cell migration, and cell cycle halt compared to the single therapies. Simultaneous treatment of HepG2 cells, with 50 µM apigenin and 5 µM sorafenib significantly enhanced the expression of apoptotic genes including caspase 3, caspase 8, caspase 10, BID, p21 and p16 as compared to their expressions in the single treatment groups [120]. These results demonstrated that the combination of apigenin and sorafenib has synergistic effects on HCC and might be considered as a promising strategy in the treatment of the inoperable HCCs.…”

Section: Sorafenibmentioning

confidence: 67%

Chemoprotective and chemosensitizing effects of apigenin on cancer therapy

et al. 2021

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Background Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. Methods We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. Results In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. Conclusion Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy. Graphical Abstract

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Investigation of possible effects of apigenin, sorafenib and combined applications on apoptosis and cell cycle in hepatocellular cancer cells

Cited by 24 publications

References 36 publications

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

Chemoprotective and chemosensitizing effects of apigenin on cancer therapy

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