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Diallyl disulfide suppresses SRC/Ras/ERK signaling-mediated proliferation and metastasis in human breast cancer by up-regulating miR-34a.

Xiao X, Chen B, Liu X, Liu P, Zheng G, Ye F, Tang H, Xie X - PLoS ONE (2014)

Bottom Line: DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects.Furthermore, Src was identified as a target of miR-34a, with miR-34a inhibiting SRC expression and consequently triggering the suppression of the SRC/Ras/ERK pathway.These results suggest that DADS could be a promising anticancer agent for breast cancer. miR-34a may also demonstrate a potential gene therapy agent that could enhance the antitumor effects of DADS.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China; Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.

ABSTRACT
Diallyl disulfide (DADS) is one of the major volatile components of garlic oil. DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects. However, the anticancer mechanisms of DADS in human breast cancer have not been elucidated, particularly in vivo. In this study, we demonstrated that the expression of miR-34a was up-regulated in DADS-treated MDA-MB-231 cells. miR-34a not only inhibited breast cancer growth but also enhanced the antitumor effect of DADS, both in vitro and in vivo. Furthermore, Src was identified as a target of miR-34a, with miR-34a inhibiting SRC expression and consequently triggering the suppression of the SRC/Ras/ERK pathway. These results suggest that DADS could be a promising anticancer agent for breast cancer. miR-34a may also demonstrate a potential gene therapy agent that could enhance the antitumor effects of DADS.

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Related in: MedlinePlus

DADS inhibits the proliferation and invasion of breast cancer cells in vitro.(A–B) MDA-MB-231 (A) and MCF-10A (B) cells treated with 0, 25, 50, 100, 200, or 400 µM DADS were seeded in 12-well plates at the desired cell concentrations and maintained in medium containing 10% fetal bovine serum. The cells were counted in triplicate at the indicated time points, and the average growth rates were calculated. *p<0.05 vs. mock, **p<0.01 vs. mock. (C) Wound healing assay using MDA-MB-231 cells treated with 200 µM DADS and analyzed after 12, 24, and 48 h. (D) Transwell invasion assay using MDA-MB-231 cells treated with 0, 25, 50, 100, 200, or 400 µM DADS and analyzed after 48 h.
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pone-0112720-g001: DADS inhibits the proliferation and invasion of breast cancer cells in vitro.(A–B) MDA-MB-231 (A) and MCF-10A (B) cells treated with 0, 25, 50, 100, 200, or 400 µM DADS were seeded in 12-well plates at the desired cell concentrations and maintained in medium containing 10% fetal bovine serum. The cells were counted in triplicate at the indicated time points, and the average growth rates were calculated. *p<0.05 vs. mock, **p<0.01 vs. mock. (C) Wound healing assay using MDA-MB-231 cells treated with 200 µM DADS and analyzed after 12, 24, and 48 h. (D) Transwell invasion assay using MDA-MB-231 cells treated with 0, 25, 50, 100, 200, or 400 µM DADS and analyzed after 48 h.

Mentions: To examine whether DADS affects breast cancer cells, duration and dose-effect experiments were performed on human breast cancer cells (MDA-MB-231) and a normal mammary epithelial cell line (MCF-10A). The results showed that DADS inhibited the proliferation of MDA-MB-231 cells in a duration- and dose-concentration manner compared with the control (Fig. 1A). DADS did not inhibit the proliferation of MCF-10A cells (Fig. 1B). Wound-healing and Transwell assays were used to assess the impact of DADS on MDA-MB-231 cell migration and invasion. Both migration (Fig. 1C) and invasion (Fig. 1D) were significantly inhibited upon exposure to different concentrations of DADS.


Diallyl disulfide suppresses SRC/Ras/ERK signaling-mediated proliferation and metastasis in human breast cancer by up-regulating miR-34a.

Xiao X, Chen B, Liu X, Liu P, Zheng G, Ye F, Tang H, Xie X - PLoS ONE (2014)

DADS inhibits the proliferation and invasion of breast cancer cells in vitro.(A–B) MDA-MB-231 (A) and MCF-10A (B) cells treated with 0, 25, 50, 100, 200, or 400 µM DADS were seeded in 12-well plates at the desired cell concentrations and maintained in medium containing 10% fetal bovine serum. The cells were counted in triplicate at the indicated time points, and the average growth rates were calculated. *p<0.05 vs. mock, **p<0.01 vs. mock. (C) Wound healing assay using MDA-MB-231 cells treated with 200 µM DADS and analyzed after 12, 24, and 48 h. (D) Transwell invasion assay using MDA-MB-231 cells treated with 0, 25, 50, 100, 200, or 400 µM DADS and analyzed after 48 h.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232521&req=5

pone-0112720-g001: DADS inhibits the proliferation and invasion of breast cancer cells in vitro.(A–B) MDA-MB-231 (A) and MCF-10A (B) cells treated with 0, 25, 50, 100, 200, or 400 µM DADS were seeded in 12-well plates at the desired cell concentrations and maintained in medium containing 10% fetal bovine serum. The cells were counted in triplicate at the indicated time points, and the average growth rates were calculated. *p<0.05 vs. mock, **p<0.01 vs. mock. (C) Wound healing assay using MDA-MB-231 cells treated with 200 µM DADS and analyzed after 12, 24, and 48 h. (D) Transwell invasion assay using MDA-MB-231 cells treated with 0, 25, 50, 100, 200, or 400 µM DADS and analyzed after 48 h.
Mentions: To examine whether DADS affects breast cancer cells, duration and dose-effect experiments were performed on human breast cancer cells (MDA-MB-231) and a normal mammary epithelial cell line (MCF-10A). The results showed that DADS inhibited the proliferation of MDA-MB-231 cells in a duration- and dose-concentration manner compared with the control (Fig. 1A). DADS did not inhibit the proliferation of MCF-10A cells (Fig. 1B). Wound-healing and Transwell assays were used to assess the impact of DADS on MDA-MB-231 cell migration and invasion. Both migration (Fig. 1C) and invasion (Fig. 1D) were significantly inhibited upon exposure to different concentrations of DADS.

Bottom Line: DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects.Furthermore, Src was identified as a target of miR-34a, with miR-34a inhibiting SRC expression and consequently triggering the suppression of the SRC/Ras/ERK pathway.These results suggest that DADS could be a promising anticancer agent for breast cancer. miR-34a may also demonstrate a potential gene therapy agent that could enhance the antitumor effects of DADS.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China; Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.

ABSTRACT
Diallyl disulfide (DADS) is one of the major volatile components of garlic oil. DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects. However, the anticancer mechanisms of DADS in human breast cancer have not been elucidated, particularly in vivo. In this study, we demonstrated that the expression of miR-34a was up-regulated in DADS-treated MDA-MB-231 cells. miR-34a not only inhibited breast cancer growth but also enhanced the antitumor effect of DADS, both in vitro and in vivo. Furthermore, Src was identified as a target of miR-34a, with miR-34a inhibiting SRC expression and consequently triggering the suppression of the SRC/Ras/ERK pathway. These results suggest that DADS could be a promising anticancer agent for breast cancer. miR-34a may also demonstrate a potential gene therapy agent that could enhance the antitumor effects of DADS.

Show MeSH
Related in: MedlinePlus