Diallyl trisulfide as an inhibitor of benzo(a)pyrene-induced precancerous carcinogenesis in MCF-10A cells

Abstract

Diallyl trisulfide (DATS) is a garlic organosulfide that is toxic to cancer cells, however, little is known about its effect in the initiation phase of carcinogenesis. We sought to determine whether DATS could inhibit the carcinogen, benzo(a)pyrene (BaP), from inducing precancerous activity, in vitro. MCF-10A cells were either pre-treated (PreTx) or concurrently treated (CoTx) with 1 μM BaP, and 6 or 60 μM DATS for up to 24 hours. The DATS 6 and 60 μM CoTx inhibited BaP-induced cell proliferation by an average of 71.1 and 120.8%, respectively, at 6 hours. The 60 μM DATS pretreatment decreased BaP-induced G2/M cell cycle transition by 127 %, and reduced the increase in cells in the S-phase by 42%; whereas 60 μM DATS CoTx induced a 177% increase in cells in G1. DATS effectively inhibited (P<0.001) BaP-induced peroxide formation by at least 54%, which may have prevented the formation of BaP-induced DNA strand breaks. In this study, we reveal mechanisms involved in DATS inhibition of BaP-induced carcinogenesis, including inhibition of cell proliferation, regulation of cell cycle, attenuation of ROS formation, and inhibition of DNA damage. At the doses evaluated, DATS appears to be an effective attenuator of BaP-induced breast carcinogenesis, in vitro.

3,6-Dihydroxyflavone Suppresses Breast Carcinogenesis by Epigenetically Regulating miR-34a and miR-21

“…The cellular breast carcinogenesis model was processed as reported previously (17). Briefly, MCF10A cells were treated with NNK and B[a]P (each at 100 pmol/L) and with different concentrations of 3,6-DHF (0, 5, 10, and 20 mmol/L); the cells were subcultured every 3 days.…”

Forkhead Box Q1 Is a Novel Target of Breast Cancer Stem Cell Inhibition by Diallyl Trisulfide

“…For example, DATS treatment inhibited DNA strand breaks induced by an environmental carcinogen (benzo-[a]pyrene) in a non-tumorigenic normal human mammary epi-thelial cell line (MCF-10A) (16). Interestingly, DATS was found to be a much more potent inducer of apoptotic cell death in MCF-7 cells compared with its monosulfide (DAS) or disulfide (DADS) analogues (18).…”

“…Cellular models have been utilized to delineate the mechanisms by which garlic constituents may inhibit breast cancer growth (15)(16)(17)(18)(19)(20). For example, DATS treatment inhibited DNA strand breaks induced by an environmental carcinogen (benzo-[a]pyrene) in a non-tumorigenic normal human mammary epi-thelial cell line (MCF-10A) (16).…”

Role of H2S Donors in Cancer Biology

“…Nkrumah-Elie and colleagues reported that DATS effectively inhibited benzo(a) pyrene (BaP)-induced carcinogenesis in noncancer breast epithelial MCF10A (Nkrumah-Elie et al 2012). BaP is a potent mutagen and carcinogen found in coal tar and cigarettes (Kaiserman and Rickert 1992).…”