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

Abstract

Abstract. 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. IntroductionIn recent years, cancer has become the leading cause of mortality, and it is detrimental to health and quality of life. Environmental chemical carcinogens have been estimated to contribute significantly to the causation of a sizable fraction, perhaps a majority, of human cancers, when exposures are correlated to 'life-style' factors, such as diet (1). Therefore, the anticancer substances in the diet have become of current interest in research for cancer prevention.Tau, chemically identified as 2-aminoethanesulfonic acid, is a sulfur-containing amino acid of a simple chemical structure. Tau accounts for ~0.1% of total human body weight and exists in a free-state in all the organs. However, the ability of endogenous Tau synthesis is limited. A large number of studies and clinical applications demonstrated that Tau has extensive physiological effects, and has been identified to be the endogenous anti-injury material. Recently, Tau has been used to in the therapy of diseases, including liver and gallbladder disease (2), cardiovascular disease (3), diabetes (4,5) and cataract (6,7). However, studies on its effect on tumors remains limited and the mechanism of its antitumor ability is ambiguous. Tau has been reported to protect cells from oxidant-induced injury by scavenging strong oxidant and cytotoxic agents (8). ...

Roles of the MST1-JNK signaling pathway in apoptosis of colorectal cancer cells induced by Taurine

“…Recent studies have shown that Tau is involved in the most important pathway related to tumor metabolism [20,21]. The anti-tumor mechanism of Tau is mainly related to Tau-induced apoptosis, synergism, and attenuation [9–13], via regulating the expression of key genes at both the transcriptional and translational levels. For example, Zhang et al showed that Tau prompted the transcription and translation of the PUMA gene in HT-29 colorectal cancer cells [10], and Sorensen et al indicated that Tau increases LRRC8A expression in wild-type A2780 cells [22]; however, the specific mechanisms underlying these effects have not been elucidated.…”

“…For example, Tau can inhibit the in vitro invasion and migration of breast cancer cells and has a better therapeutic effect against methylbenzanthracene (DMBA)-induced breast cancer [11,12]. Our previous studies have shown that Tau can inhibit the apoptosis of cardiomyocytes subjected to ischemia/reperfusion [15] and can induce (or promote) apoptosis in colon cancer [10], breast cancer [13,14], or liver cancer cells [12]. This effect is achieved by up-regulating the expression of BCL-2, PMA, and P53, while down-regulating the expression of BCL-2.…”

Metabolic Portraits of Breast Cancer by HR MAS MR Spectroscopy of Intact Tissue Samples

“…ER- and HER2+ tumors are generally more aggressive, and when comparing patients with a poor or good prognosis based on clinical parameters (lymphatic spread, tumor size and hormone receptor status) lower taurine levels in tissue from the poor-prognosis patients were detected [39]. A study using two different human breast cancer cell lines showed that treating cells with taurine inhibited growth and induced apoptosis by regulating apoptosis-related proteins of mitochondria [73]. …”

Taurine abrogates mammary carcinogenesis through induction of apoptosis in Sprague‐Dawley rats

“…Taurine has been found to maintain the level of cysteine, an essential precursor of glutathione and also acts as an antioxidant . Studies have revealed the anticancer and apoptosis‐inducing role of taurine in cancer cells . Inclusion of a small amount of taurine to drinking water has been shown to extend the mean lifespan of mice with transplanted tumors, with a tumor growth inhibition rate of 42.26% .…”

“…Inclusion of a small amount of taurine to drinking water has been shown to extend the mean lifespan of mice with transplanted tumors, with a tumor growth inhibition rate of 42.26% . It has been reported that taurine Schiff base copper complex effectively inhibited the activity of purified 20S and 26S proteasomes in human breast cancer MDA‐MB‐231 and leukemia Jurkat T‐cells, which results in the accumulation of ubiquitinated protein and the proteasome target proteins p27 and Bax, followed by the induction of apoptosis …”