Diallyl Sulfide Attenuation of Carcinogenesis in Mammary Epithelial Cells through the Inhibition of ROS Formation, and DNA Strand Breaks

Abstract

Garlic has long been used medicinally for many diseases, including cancer. One of the active garlic components is diallyl sulfide (DAS), which prevents carcinogenesis and reduces the incidence rate of several cancers. In this study, non-cancerous MCF-10A cells were used as a model to investigate the effect of DAS on Benzo (a)pyrene (BaP)-induced cellular carcinogenesis. The cells were evaluated based on changes in proliferation, cell cycle arrest, the formation of peroxides, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, the generation of DNA strand breaks, and DNA Polymerase β (Pol β) expression. The results obtained indicate that when co-treated with BaP, DAS inhibited BaP-induced cell proliferation (p < 0.05) to levels similar to the negative control. BaP treatment results in a two-fold increase in the accumulation of cells in the G2/M-phase of the cell cycle, which is restored to baseline levels, similar to untreated cells and vehicle-treated cells, when pretreated with 6 μM and 60 μM DAS, respectively. Co-treatment with DAS (60 μM and 600 μM) inhibited BaP-induced reactive oxygen species (ROS) formation by 132% and 133%, respectively, as determined by the accumulation of H2O2 in the extracellular medium and an increase in 8-OHdG levels of treated cells. All DAS concentrations inhibited BaP-induced DNA strand breaks through co-treatment and pre-treatment methods at all time points evaluated. Co-Treatment with 60 μM DAS increased DNA Pol β expression in response to BaP-induced lipid peroxidation and oxidative DNA damage. These results indicate that DAS effectively inhibited BaP-induced cell proliferation, cell cycle transitions, ROS, and DNA damage in an MCF-10A cell line. These results provide more experimental evidence for garlic’s antitumor abilities and corroborate many epidemiological studies regarding the association between the increased intake of garlic and the reduced risk of several types of cancer.

The Garlic Compound, Diallyl Trisulfide, Attenuates Benzo[a]Pyrene-Induced Precancerous Effect through Its Antioxidant Effect, AhR Inhibition, and Increased DNA Repair in Human Breast Epithelial Cells

“…Thus, the concentrations used in this study are well within tolerated physiological ranges in humans. Our lab and others have previously reported that DATS affects chemical-induced carcinogenesis through the modulation of aqueous peroxides, the induction of cell cycle arrest, and DNA damage in breast epithelial cells [ 13 , 21 , 22 , 25 ]. Thus, the focus of this study was to provide further evidence of DATS’ attenuation on B[a]P-induced precancerous activities through alterations in cell proliferation, clonogenic formation, ROS formation that can lead to DNA damage, and interplay between the various proteins expressed (AhR, HIF-1β, CYP1A1, and DNA POLβ) as indicators of DNA damage which may lead to mutations and neoplastic transformation of B[a]P-treated normal breast epithelial MCF-10A cells.…”

“…8-OHdG was measured using the EpiQuik 8-OHdG DNA Damage Quantification Direct Kit (Colorimetric), and the method used in prior studies [ 21 ] was followed.…”

From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment

“…38 Regarding breast cancer, 4 has been shown to effectively inhibit tumor cell proliferation, control cell cycle transitions, decrease lipid peroxidation, and attenuate DNA strand breaks. 39,41 Combination therapy with 4 and paclitaxel (18) in rats with induced skin cancer not only effectively reduced Bcl-2 protein expression and increased p53 gene expression but also restored skin architecture. 42 In another study, rats with induced benign prostatic hyperplasia (BPH) were treated either with 4 (50 mg/kg, p.o.)…”

“…DAS ( 4 ), a fat-soluble compound present in garlic, has demonstrated anticancer activity against hepatocellular, breast, − skin, and prostate carcinomas. In vivo studies carried out in nude mice injected with human hepatocellular carcinoma (HCC) HepG2 cells and treated with 4 revealed that it inhibited the growth and clonogenicity of HepG2 and Huh7 HCC cells.…”

“…The expression levels of ER-α36 and epidermal growth factor receptor (EGFR) were also analyzed, and it was found that ER-α36 signaling is involved in the inhibition of HCC cell growth induced by 4 both in vitro and in vivo . Regarding breast cancer, 4 has been shown to effectively inhibit tumor cell proliferation, control cell cycle transitions, decrease lipid peroxidation, and attenuate DNA strand breaks. , Combination therapy with 4 and paclitaxel ( 18 ) in rats with induced skin cancer not only effectively reduced Bcl-2 protein expression and increased p53 gene expression but also restored skin architecture …”