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Abstract
Diallyl disulfide (DADS), a garlic organosulfur compound, has been researched as a cancer prevention agent; however, the role of DADS in the suppression of cancer initiation in nonneoplastic cells has not been elucidated. To evaluate DADS inhibition of early carcinogenic events, MCF-10A cells were pretreated (PreTx) with DADS followed by the ubiquitous carcinogen benzo(a)pyrene (BaP), or cotreated (CoTx) with DADS and BaP for up to 24 h. The cells were evaluated for changes in cell viability/proliferation, cell cycle, induction of peroxide formation, and DNA damage. BaP induced a statistically significant increase in cell proliferation at 6 h, which was attenuated with DADS CoTx. PreTx with 6 and 60 μM of DADS inhibited BaP-induced G2/M arrest by 68% and 78%, respectively. DADS, regardless of concentration or method, inhibited BaP-induced extracellular aqueous peroxide formation within 24 h. DADS attenuated BaP-induced DNA single-strand breaks at all time points through both DADS Pre- and CoTx, with significant inhibition for all treatments sustained after 6 h. DADS was effective in inhibiting BaP-induced cell proliferation, cell cycle transitions, reactive oxygen species, and DNA damage in a normal cell line, and thus may inhibit environmentally induced breast cancer initiation.
ACKNOWLEDGMENTS
This research is a continuation of the legacy and mission of the late Dr. Ronald D. Thomas; we love you and we miss you. We would like to acknowledge the Florida Agricultural and Mechanical University College of Pharmacy and Pharmaceutical Sciences Faculty and Staff, especially Drs. Karam Soliman, Barak Abonyo, Carl Goodman, and Tracy Womble for their assistance, and use of their supplies and equipment. Additionally, we would like to thank the Florida Education Fund's McKnight Doctoral Fellowship Program for honoring Dr. Yasmeen Nkrumah-Elie as a McKnight Fellow. This study was funded in part by NIH RCMI Grant # 8 G12 MD007582-28.