title: Resveratrol enhances the efficacy of sorafenib mediated apoptosis in human breast cancer MCF7 cells through ROS, cell cycle inhibition, caspase 3 and PARP cleavage.
abstract: Despite advances in diagnosis and treatment options, breast cancer is one of the main causes of cancer related death among women worldwide. Present study is aimed to preliminarily evaluate our hypothesis that the combination of resveratrol (RSV), a natural antioxidant, and lower dose of sorafenib (SF), a multi-kinase inhibitor and a component of ERK1/2 (extracellular signal-regulated kinase 1/2) pathway, would augment apoptosis in human breast cancer MCF7 cells. MCF7 cellexpressions s were treated with RSV, SF and their combination. MTT (3-[4,5-dimethylthiazol-2-yl] -2, 5-diphenyl-tetrazolium bromide) assay, DNA fragmentation assay, Hoechst33342, H2DCFDA (2', 7'-Dichlorodihydrofluorescein diacetate), Rhodamine123 staining, and Western Blot to detect different signaling protein expressions, were conducted to test the hypothesis. Combination of RSV and SF showed higher cytotoxicity on MCF7 cells than their individual treatment. Results from morphology change, Hoechst33342 staining, and DNA fragmentation suggested higher apoptosis data in the combinational treatment. Intracellular ROS (reactive oxygen species) levels, p53 and Bax/Bcl2 expressions, and decrease in mitochondrial membrane potential were also higher in the combinational treatment. Up-regulation of apaf-1, cl. caspase 9, cl. caspase 3 and cl. PARP (poly (ADP-Ribose) polymerase) were also noticed, while the expressions of cyclinD1 and cyclinB1 were decreased in the combinational group. The increase in apoptosis and signaling protein expressions with RSV and SF combinational treatment were increased over time. The combination of RSV and lower dose of SF at 6μM showed enhanced apoptotic activity than SF alone. Therefore, RSV can be considered as a neo-adjuvant to improve SF efficacy in breast cancer treatment.
authors.affiliation: Union University School of Pharmacy, Jackson, TN 38305, United States; College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Dyson Pharmacy Building, Tallahasse, FL 32307, United States. Electronic address: arndmmndl@gmail.com.
authors.forename: Arindam
authors.initials: A
authors.lastname: Mondal
authors.affiliation: Union University School of Pharmacy, Jackson, TN 38305, United States. Electronic address: llbennett@uu.edu.
authors.forename: Lunawati L
authors.initials: LL
authors.lastname: Bennett
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D053148:Caspase 3 / Q000096:biosynthesis*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D000077157:Sorafenib; D013267:Stilbenes / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010671:Phenylurea Compounds; D017382:Reactive Oxygen Species; D013267:Stilbenes; D009536:Niacinamide; D000077157:Sorafenib; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D000077185:Resveratrol
keywords: Apoptosis; Cell cycle inhibition; MCF7; ROS; Resveratrol; Sorafenib