Avaliação do Efeito Antiproliferativo de Bischalconas Sintéticas Inéditas (L01 E L03) em Células Tumorais e Não Tumorais

Abstract

Cancer is considered to be a multifactorial disease of a mutational and proliferative nature that involves the disorganized growth of cells with a high invasive capacity, which can spread to tissues and organs. Many efforts have been made to find new compounds that are effective in the treatment of cancer and chalcones have recently stood out as promising due to their anticancer potential. However, studies reporting their cytotoxic and cytostatic activity are still scarce. In this context, this work aims to evaluate the antiproliferative effect of (synthetic) bischalcones L01 and L03 on tumor cell lines and the mechanisms of action involved in their inhibitory activity, through in vitro assays. The samples (L01 and L03) were tested on eight

tumor cell lines (NCI-H460, Mel501, B16-F10, MDA-MB-231, HCT-116, HL-60, KG-1a, K- 562) and two non-tumor cell lines (L929 and MCF10a) using the MTT method in serial

concentrations for 24, 48 and 72 hours. Through the MTT test, after 72 h of treatment, it was observed that the samples obtained CI50 values ranging from 9.25 to 78.8 μM in tumor cells and 47.6 μM in non-tumor cells. In view of the results, the bischalcone sample (L01) was chosen to continue the tests on the HCT-116 human colon tumor line. Initially, pulse treatment of the compound (L01) was carried out for 24 and 48 hours, however, the sample did not show a time-dependent profile. After the MTT tests, the cytotoxic profile of the sample was evaluated using the trypan blue test, where we found that the concentrations of 8 and 16 μM interfered with the viability of the HCT-116 cells after 24 hours. Morphological analysis using rapid panoptic staining revealed alterations at concentrations of 4, 8 and 16 μM, such as cell rarefaction, alterations to the cytoplasmic membrane, mitotic figures, vacuoles and the

appearance of some cells with apoptotic bodies. That said, the cytotoxic effect of L01 on HCT- 116 cells may possibly be related to the induction of cell death by apoptosis, autophagy and/or anoikis.