Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 50, Issue 7, Pages 2524-2530Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2012.04.010
Keywords
Benzo(a)pyrene; Diallyl trisulfide; Early carcinogenesis; Breast cancer; MCF-10A; In vitro
Categories
Funding
- NIH [8 G12 MD007582-28, 2 G12 RR003020]
- Florida Education Fund's McKnight Doctoral Program
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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 mu M Bat,. and 6 or 60 mu M DATS for up to 24 h. The DATS 6 and 60 mu M CoTx inhibited BaP-induced cell proliferation by an average of 71.1% and 120.8%, respectively, at 6 h. The 60 mu M 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 mu M 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. (C) 2012 Elsevier Ltd. All rights reserved.
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