Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria

Таурин индуцирует апоптоз клеток рака молочной железы путем регуляции митохондриальных белков, связанных с апоптозом
Xiali Zhang, Fusheng Wan, Hongfei Lu, Yibing Wang, Chunju Liu, Weifeng Zhu, Shuangyan Zheng
2014-11-13

Bax and Bcl-2 regulationPUMA (p53-upregulated modulator of apoptosis)Taurinebreast cancer apoptosiscaspase-3 activation
Taurine (Tau), the most abundant free amino acid in humans has numerous potential health benefits through its antioxidant and anti-inflammatory properties. However, limited studies have assessed its effect on tumors and the antitumor mechanism remains unknown. The present study investigated the cellular and molecular changes induced by Tau, leading to the induction of apoptosis in human breast cancer cell lines MCF-7 and MDA-MB-231. MCF-7 is p53 proficient (p53+/+) and MDA-MB-231 is a p53 null mutant (p53-/-). Cell proliferation and viability were assessed by MTT. Flow cytometry and hoechst33342 fluorescent staining were employed to detect apoptosis. Spectrophotometry was used to detect caspase-3 activity. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect the levels of mRNA and proteins of p53-upregulated modulator of apoptosis (PUMA), Bax and Bcl-2. Finally, the affect of Tau on the growth of MDA-MB-231-cell-nude mice xenografts was examined. In the study, Tau inhibited growth and induced apoptosis of the two cell lines in a concentration- and time-dependent manner. Notably, the inhibitory effect of Tau on p53-/- cancer cells was clearly significant compared to the p53+/+ cancer cells. Further studies showed that Tau promoted apoptosis in human breast cancer cells and inhibited the growth of tumor in nude mice by inducing the expression of PUMA, which further up- and downregulated the expression of Bax and Bcl-2 protein, giving rise to increased activation of caspase-3. Collectively, these results indicate that Tau is a potent candidate for the chemotherapy of breast cancer through increasing the PUMA expression independent of p53 status.
1
Taurine has a more significant inhibitory effect on p53-null (MDA-MB-231) cancer cells compared to p53-proficient (MCF-7) cells.
2
Taurine increases PUMA expression and promotes apoptosis independent of p53 status, suggesting therapeutic potential for breast cancer chemotherapy.
3
Taurine induces apoptosis by upregulating PUMA expression, which increases Bax, decreases Bcl-2, and leads to increased caspase-3 activation.
4
Taurine inhibits growth of MDA-MB-231 xenograft tumors in nude mice, demonstrating in vivo antitumor efficacy.
5
Taurine inhibits proliferation and induces apoptosis in human breast cancer cell lines MCF-7 and MDA-MB-231 in a concentration- and time-dependent manner.

Taurine-induced effects on human breast cancer cells (MCF-7 and MDA-MB-231) and MDA-MB-231 nude-mouse xenografts

Induction of apoptosis via regulation of mitochondrial apoptosis-related proteins (PUMA, Bax, Bcl-2) and consequent caspase-3 activation, and inhibition of tumor growth, including p53-independent upregulation of PUMA

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2014-11-13
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Xiali Zhang
Fusheng Wan
Hongfei Lu
Yibing Wang
Chunju Liu
Weifeng Zhu
Shuangyan Zheng
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