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Effects of cis-trimethoxystilbene treatment after TP53 silencing by siRNA in the tumoral cell lines MCF-7 and MDA-MB-231: a cellular and molecular approach

Grant number: 18/16461-0
Support type:Regular Research Grants
Duration: September 01, 2020 - August 31, 2022
Field of knowledge:Health Sciences - Pharmacy - Pharmacognosy
Principal Investigator:Raquel Alves dos Santos
Grantee:Raquel Alves dos Santos
Home Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil
Assoc. researchers:Cássia Suemi Mizuno

Abstract

Natural products continue to be the largest source for obtaining molecules with biological potential for the development of new drugs. Among these molecules are those belonging to the stilbene group. Being resveratrol the stilbene with widely studied biological activity and great pharmacological potential for cancer therapy, its low bioavailability has limited the progress of its use in more advanced clinical trials. To overcome this problem, resveratrol methoxy derivatives were synthesized, including the cis-trimethoxystilbene (cis-TMS), that demonstraded higher bioavailabilty and antiproliferative effects than its original precursor. Although the expressive antiproliferative effects of cis-TMS in tumoral cell lines the role of p53 protein in this biological activity is not clear. Considering its great pharmacological potential, once we demonstrated the induction of DNA damage and cell death is response to the treatment with very low concentrations of cis-TMS (<2.5 µM), the main objective of the present project is to evaluate the cellular responses of cis-TMS treatment after inhibition of TP53 gene using siRNA in two tumoral breast cell lines (MCF-7 and MDA-MB-231, as well as in its normal counterpart MCF-10A. It is expected to answer the question: is the antiproliferative effects of cis¬-TMS dependent of p53? (AU)