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

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 h. The DATS 6 and 60 μM CoTx inhibited BaP-induced cell proliferation by an average of 71.1% and 120.8%, respectively, at 6 h. 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.

► BaP induces changes in cell viability and cell growth in MCF-10A cells. ► BaP induces peroxide formation and DNA strand breaks in MCF-10A cells. ► DATS inhibits BaP-induced cell proliferation and cell cycle changes. ► DATS inhibits BaP-induced peroxide formation in MCF-10A cells. ► DATS inhibits BaP-induced DNA strand breaks in MCF-10A cells.