Avaliação da atividade antitumoral de análogos de curcumina sobre células derivadas de câncer de mama

Abstract

Breast cancer represents the first cause of cancer death among women worldwide. Approximately 75% of diagnosed breast tumors express estrogen receptors (ER+) and, in this case, hormonal therapy is considered the first line treatment. However, some tumors are resistant or became resistant to the drugs conventionally used in the therapeutic proposals and, therefore, it is necessary to identify new compounds to improve therapeutic proposals for breast cancer. The natural compounds are important source for the identification of new compounds with antitumor activity, since they produce a wide variety of secondary metabolites. In a previous study performed by our research group was demonstrated that 3 curcumin analogues (PQM-162, PQM-163, and PQM-164) significantly reduced cell viability in MCF-7 cultures, which are derived from RE positive-breast cancer. In addition, it has been demonstrated that PQM-162 inhibits cell cycle progression due to its ability of gene expression profile of critical cell cycle regulator of G2/M transition and mitosis onset. However, the mechanism associated to cytotoxic activity of PQM-162 on MCF-7 is not investigated. Furthermore, the effects of PQM-163 and PQM-164 are not explored. Thus, the present study aimed to evaluate the effects of the substances PQM-163 and PQM-164 on proliferative behavior of MCF-7 cells and to compare those observed for PQM-162. In addition, the activity profile of the studied substances was evaluated on Hs578t and MDA-MB-231 triple negative cells, which represent a breast tumor subtype with limited clinical proposal due to absence of therapeutic targets. The pro-apoptotic activity of studied substances was also evaluated on MCF-7, Hs578t, and MDA-MV-231. We found that PQM-163 and PQM-164 inhibit cell cycle similarly to PQM-162, however the potency of PQM-163 and PQM-164 was lower than PQM-162. Triple negative cell lines were more resistance to treatment compared to MCF-7 cell line. Apart from this, we observed that PM-163 and PQM-164 efficiently inhibited cell cycle progression in triple negative breast cancer cells. In addition, the PQM-164 molecule efficiently sensitized the doxorubicin resistant MCF-7 (DXR-R) cells to the drug. These findings are very promising and support further in vivo studies to validate antitumor activity and to investigate the pharmacokinetic and pharmacodynamics profiles of the substances PQM-162, PQM-163, and PQM-164.