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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 growth and invasion by up-regulating miR-34a in breast cancer cells.(A) MDA-MB-231 cells were exposed to 0, 25, 50, 100, 200, or 400 µM DADS for 48 h, and the expression of miR-34a was assessed by qRT-PCR. Triplicate assays were performed for each RNA sample, and the relative miRNA levels were normalized to U6 snRNA. *p<0.05 vs. mock, **p<0.01 vs. mock. (B) MDA-MB-231 cells treated with 200 µM DADS and transfected with miR-34a mimics or scramble control miRNA 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. (D) Transwell invasion assay using MDA-MB-231 cells treated with scramble control, miR-34a mimics, mock or miR-34a plus 200 µM DADS and analyzed after 48 h.
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pone-0112720-g002: DADS inhibits growth and invasion by up-regulating miR-34a in breast cancer cells.(A) MDA-MB-231 cells were exposed to 0, 25, 50, 100, 200, or 400 µM DADS for 48 h, and the expression of miR-34a was assessed by qRT-PCR. Triplicate assays were performed for each RNA sample, and the relative miRNA levels were normalized to U6 snRNA. *p<0.05 vs. mock, **p<0.01 vs. mock. (B) MDA-MB-231 cells treated with 200 µM DADS and transfected with miR-34a mimics or scramble control miRNA 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. (D) Transwell invasion assay using MDA-MB-231 cells treated with scramble control, miR-34a mimics, mock or miR-34a plus 200 µM DADS and analyzed after 48 h.

Mentions: In a previous study, we confirmed microarray expression data showing up-regulation of miR-34a by DADS treatment in gastric cancer cell lines [9]. Here, qRT-PCR was used to measure the expression of miR-34a in MDA-MB-231 cells exposed to 0, 25, 50, 100, 200 or 400 µM DADS for 48 h. miR-34a expression was up-regulated with increasing doses of DADS (Fig. 2A). Next, MDA-MB-231 cells were transfected with a scramble miRNA control, miR-34a mimics or miR-34a plus 200 µM DADS and counted after 48 h. The results of this assay suggested that miR-34a mimics could inhibit MDA-MB-231 cell proliferation. The anti-proliferation effect was more obvious when the MDA-MB-231 cells were transfected with miR-34a and treated with 200 µM DADS (Fig. 2B). The Transwell assay results showed that the combined treatment of miR-34a mimics with DADS synergistically inhibited breast cancer cell invasion (Fig. 2C).


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 growth and invasion by up-regulating miR-34a in breast cancer cells.(A) MDA-MB-231 cells were exposed to 0, 25, 50, 100, 200, or 400 µM DADS for 48 h, and the expression of miR-34a was assessed by qRT-PCR. Triplicate assays were performed for each RNA sample, and the relative miRNA levels were normalized to U6 snRNA. *p<0.05 vs. mock, **p<0.01 vs. mock. (B) MDA-MB-231 cells treated with 200 µM DADS and transfected with miR-34a mimics or scramble control miRNA 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. (D) Transwell invasion assay using MDA-MB-231 cells treated with scramble control, miR-34a mimics, mock or miR-34a plus 200 µM DADS and analyzed after 48 h.
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Show All Figures
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pone-0112720-g002: DADS inhibits growth and invasion by up-regulating miR-34a in breast cancer cells.(A) MDA-MB-231 cells were exposed to 0, 25, 50, 100, 200, or 400 µM DADS for 48 h, and the expression of miR-34a was assessed by qRT-PCR. Triplicate assays were performed for each RNA sample, and the relative miRNA levels were normalized to U6 snRNA. *p<0.05 vs. mock, **p<0.01 vs. mock. (B) MDA-MB-231 cells treated with 200 µM DADS and transfected with miR-34a mimics or scramble control miRNA 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. (D) Transwell invasion assay using MDA-MB-231 cells treated with scramble control, miR-34a mimics, mock or miR-34a plus 200 µM DADS and analyzed after 48 h.
Mentions: In a previous study, we confirmed microarray expression data showing up-regulation of miR-34a by DADS treatment in gastric cancer cell lines [9]. Here, qRT-PCR was used to measure the expression of miR-34a in MDA-MB-231 cells exposed to 0, 25, 50, 100, 200 or 400 µM DADS for 48 h. miR-34a expression was up-regulated with increasing doses of DADS (Fig. 2A). Next, MDA-MB-231 cells were transfected with a scramble miRNA control, miR-34a mimics or miR-34a plus 200 µM DADS and counted after 48 h. The results of this assay suggested that miR-34a mimics could inhibit MDA-MB-231 cell proliferation. The anti-proliferation effect was more obvious when the MDA-MB-231 cells were transfected with miR-34a and treated with 200 µM DADS (Fig. 2B). The Transwell assay results showed that the combined treatment of miR-34a mimics with DADS synergistically inhibited breast cancer cell invasion (Fig. 2C).

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