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Synergistic effect of sorafenib and resveratrol in human breast cancer MDA‐MB‐231 cells
Author(s) -
lo bennett lunawati
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02759
Subject(s) - breast cancer , cancer , resveratrol , sorafenib , pancreatic cancer , medicine , cancer cell , cancer research , viability assay , apoptosis , curcumin , pharmacology , biology , hepatocellular carcinoma , biochemistry
The incidence of breast cancer mortality is one of the major challenges in the scientific community. Despite advances in diagnosis and treatment options, death among women worldwide are still high. The desired outcome of the cancer therapies is to increase cellular apoptosis, to decrease the proliferative activity of the cancer cells, to minimize drug resistance, and to decrease the toxicity of the anticancer drugs. Sorafenib (SF), a component of ERK1/2 pathway, is a multi‐kinase inhibitor that target VEGFR‐1, VEGFR‐3, PDGFR‐h, and others. SF has been shown in the previous preclinical studies to slow cancer progression in human hepatocellular, renal, colon, pancreatic, thyroid, ovarian, lung, and breast cancer. The use of natural dietary antioxidants such as curcumin, resveratrol (RSV) in cancer treatment has gained popularity due to their minimal cytotoxic effects with no evidence of causing damage to normal cellular tissue. RSV is a natural polyphenol compound found in red grapes, berries, peanuts and other fruits with anti‐oxidant and chemo‐preventive properties. Several studies mentioned that RSV possesses potent anti‐cancer activity against human breast cancer by inhibiting cancer initiation, promotion, and progression. In the present study, RSV was studied as a chemo‐enhancing potential agent in combination with low dose of SF for the treatment of breast cancer using MDA‐MB‐231 cells. Cells viability measured by MTT assay (3‐[4, 5‐dimethylthiazol‐2‐yl] ‐2, 5‐diphenyl‐tetrazolium bromide), Hoechst33342, H 2 DCFDA, and Rhodamine123 staining using fluorescent microscope were conducted to determine cell viability, chromatin inducing apoptosis, intracellular generation of ROS, and mitochondrial membrane potential, respectively. Western Blot to detect different signaling protein expressions such as Casp‐3, Casp‐9, Casp‐8, P53, Bax, Bcl2, Apaf‐1, Smac/Diablo, MMP2, BRCA1, BRCA2, Bim, and Map kinases were conducted to test the hypothesis that RSV has efficacy with low dose of SF to decrease cancer cell proliferation and progression. The concentration of SF used was 3 μM and RSV was 50 μM. This finding suggests RSV can potentiate SF as anticancer drug in breast cancer treatment. Support or Funding Information Union University College of Pharmacy