title: Evaluation of growth inhibitory response of Resveratrol and Salinomycin combinations against triple negative breast cancer cells.
abstract: Resveratrol (RSVL) a dietary phytochemical showed to enhance the efficacy of chemotherapeutic drugs. Recently, Salinomycin (SAL) has gained importance as cancer therapeutic value for breast cancer (BC), however, its superfluxious toxicity delimits the utility. Taking the advantage of RSVL, the therapeutic efficacy of RSVL and SAL combination was studied in vitro and in vivo system. Firstly, the synergistic combination dose of RSVL and SAL was calculated and further, the efficacy was examined by wound healing, and Western blots analysis. Further, in vivo study was performed to confirm the effect of colony formation and apoptosis detection by flow cytometry based assays. Further, the molecular mode of action was determined at both transcript and translational level by quantitative Real Time PCR combination in Ehrlich ascitic carcinoma model.The combination of IC20 (R20) of RSVL and IC10 (S10) dose of SAL showed best synergism (CI<1) with ∼5 fold dose advantage of SAL. Gene expression results at mRNA and protein level revealed that the unique combination of RSVL and SAL significantly inhibited epithelial mesenchymal transition (Fibronectin, Vimentin, N-Cadherin, and Slug); chronic inflammation (Cox2, NF-kB, p53), autophagy (Beclin and LC3) and apoptotic (Bax, Bcl-2) markers. Further, i n vivo study showed that low dose of SAL in combination with RSVL increased life span of Ehrlich ascitic mice. Overall, our study revealed that RSVL synergistically potentiated the anticancer potential of SAL against triple negative BC.
authors.affiliation: Proteomics and Environmental Carcinogenesis Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31 Vishvigyan Bhawan, M. G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR) CSIR-IITR Campus, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Girish
authors.initials: G
authors.lastname: Rai
authors.affiliation: Proteomics and Environmental Carcinogenesis Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31 Vishvigyan Bhawan, M. G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR) CSIR-IITR Campus, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Shankar
authors.initials: S
authors.lastname: Suman
authors.affiliation: Proteomics and Environmental Carcinogenesis Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31 Vishvigyan Bhawan, M. G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR) CSIR-IITR Campus, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Proteomics and Environmental Carcinogenesis Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31 Vishvigyan Bhawan, M. G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR) CSIR-IITR Campus, Lucknow 226001, Uttar Pradesh, India. Electronic address: yshukla@iitr.res.in.
authors.forename: Yogeshwer
authors.initials: Y
authors.lastname: Shukla
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000095662:Polyether Polyketides
chemical_list: D015820:Cadherins; D016328:NF-kappa B; D011714:Pyrans; D000077185:Resveratrol; D013267:Stilbenes; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Apoptosis; Autophagy; Epithelial mesenchymal transition; Resveratrol; Salinomycin