ArticleOncotarget2015
Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 89 citations in OpenAlex.
- K-Homology Splicing Regulatory Protein (KSRP) Augments Survival and Proliferation of Human Melanoma Cells.Current issues in molecular biology · 2025Article
- Enhancement of apoptosis in HCT116 and HepG2 cells byChinese herbal medicines · 2025Article
- Fisetin as a chemoprotective and chemotherapeutic agent: mechanistic insights and future directions in cancer therapy.Medical oncology (Northwood, London, England) · 2025Review
- Antioxidant Senotherapy by Natural Compounds: A Beneficial Partner in Cancer Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- The Role of Nutraceuticals in Chemoprevention and their Therapeutic Effects when used in Combination with Synthetic Drugs.Current medicinal chemistry · 2025Review
- Modulation ofPeerJ · 2025Article
- Medicinal plants as a potential resource for the discovery of novel structures towards cancer drug resistance treatment.Heliyon · 2024Review
- Aspirin-Fisetin Combinatorial Treatment Exerts Cytotoxic and Anti-Migratory Activities in A375 Malignant Melanoma Cells.Medicina (Kaunas, Lithuania) · 2024Article
- Melanoma-derived soluble mediators modulate neutrophil biological properties and the release of neutrophil extracellular traps.Cancer immunology, immunotherapy : CII · 2023Article
- Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies.Global medical genetics · 2023Review
- Complementary and alternative therapies in skin cancer a literature review of biologically active compounds.Dermatologic therapy · 2022Review
- Article
- Diet-derived small molecules (nutraceuticals) inhibit cellular proliferation by interfering with key oncogenic pathways: an overview of experimental evidence in cancer chemoprevention.Biologia futura · 2022Review
- Angioprevention of Urologic Cancers by Plant-Derived Foods.Pharmaceutics · 2022Review
- Synthesis, inverse docking-assisted identification and in vitro biological characterization of Flavonol-based analogs of fisetin as c-Kit, CDK2 and mTOR inhibitors against melanoma and non-melanoma skin cancers.Bioorganic chemistry · 2021Article
- Follicle inhibition at the primordial stage without increasing apoptosis, with a combination of everolimus, verapamil.Molecular biology reports · 2020Article
- Adaptive redox homeostasis in cutaneous melanoma.Redox biology · 2020Review
- Article
- Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies.Cancers · 2020Review
- Combination treatment of gemcitabine and sorafenib exerts a synergistic inhibitory effect on non-small cell lung cancerOncology letters · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Melanoma is the most deadly form of cutaneous malignancy, and its incidence rates are rising worldwide. In melanoma, constitutive activation of the BRAF/MEK/ERK (MAPK) and PI3K/AKT/mTOR (PI3K) signaling pathways plays a pivotal role in cell proliferation, survival and tumorigenesis. A combination of compounds that lead to an optimal blockade of these critical signaling pathways may provide an effective strategy for prevention and treatment of melanoma. The phytochemical fisetin is known to possess anti-proliferative and pro-apoptotic activities. We found that fisetin treatment inhibited PI3K signaling pathway in melanoma cells. Therefore, we investigated the effect of fisetin and sorafenib (an RAF inhibitor) alone and in combination on cell proliferation, apoptosis and tumor growth. Combination treatment (fisetin + sorafenib) more effectively reduced the growth of BRAF-mutated human melanoma cells at lower doses when compared to individual agents. In addition, combination treatment resulted in enhanced (i) apoptosis, (ii) cleavage of caspase-3 and PARP, (iii) expression of Bax and Bak, (iv) inhibition of Bcl2 and Mcl-1, and (v) inhibition of expression of PI3K, phosphorylation of MEK1/2, ERK1/2, AKT and mTOR. In athymic nude mice subcutaneously implanted with melanoma cells (A375 and SK-MEL-28), we found that combination therapy resulted in greater reduction of tumor growth when compared to individual agents. Furthermore, combination therapy was more effective than monotherapy in: (i) inhibition of proliferation and angiogenesis, (ii) induction of apoptosis, and (iii) inhibition of the MAPK and PI3K pathways in xenograft tumors. These data suggest that simultaneous inhibition of both these signaling pathways using combination of fisetin and sorafenib may serve as a therapeutic option for the management of melanoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.