Estudo do potencial antitumoral de derivados da pterocarpanoquinona LQB-118 em linhagens celulares de câncer de próstata

Abstract

According to the World Health Organization, prostate cancer is among the most common, and in Brazil, it is the second most common among men. Knowing that this is a very resistant type of cancer, the search for new therapeutic alternatives becomes crucial. Previous studies have shown important cytotoxic activity of the pterocarpanoquinone LQB-118 on leukemic cell lines and prostatic tumors. Aiming to seek new molecules with cytotoxic action for prostate cancer, a set of molecules derived from LQB-118 was synthesized and evaluated for its cytotoxicity in this type of cancer. The molecules LQB-471, LQB-472, LQB-473, LQB-474 and LQB-475 were synthesized, and cytotoxicity was analyzed by the MTT assay in hormone sensitive (LNCaP) and resistant (PC3) tumor cell lines and non-tumor cell line (Vero). Cell viability was determined by the Tripan Blue dye exclusion assay. Cytotoxic action screening showed that LQB-471, LQB-472 and LQB-474 derivatives induced cytotoxicity on the prostatic tumor cells LNCaP and PC3 at 10 μM, in 48 h, with LQB-472 being the most active one. The last induced inhibitions of 75,6% and 84,5% on the mitochondrial reducing activity of such cells, respectively. The derivatives LQB-471, LQB-472 and LQB-474 presented IC50 values of 12,46, 5,98 and 26,36 μM, respectively, for LNCaP cells, and 16,58, 3,30 and 28,53 μM, respectively, for PC3 cells, in 48 h. Since LBQ-472 presented the highest cytotoxic action, its studies were then continued, showing time-dependent cytotoxic action on LNCaP and PC3 cells. The best incubation time with LQB-472 was 72 h, with cytotoxicity of 90,4% for LNCaP cells and 96,2% for PC3, at 10 μM, presenting IC50 of 1,26μM and 0,96 μM, respectively, in 72 h. Vero non-tumor cell line showed IC50 value (7,14 μM) higher than the tumor lines, in 72 h. The use of the trypan blue dye exclusion technique showed that LQB-472 also inhibits proliferation of both tumor cell lines. In conclusion, the LQB-472 derivative, the only one that has two quinone groups in its structure, showed the greatest cytotoxic effect on prostate tumor cells, with the hormone-resistant cell line (PC3) being more sensitive than the responsive one (LNCaP). In addition, this derivative induced low cytotoxicity for healthy cells, indicating an important therapeutic potential for LQB-472 in prostate cancer