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

Abstract

The aim of this study was to observe the impact of the mammalian sterile 20-like kinase 1-c-Jun N-terminal kinase (MST1-JNK) signaling pathway on apoptosis in colorectal cancer (CRC) cells induced by Taurine (Tau). Caco-2 and SW620 cells transfected with p-enhanced green fluorescent protein (EGFP)-MST1 or short interfering RNA (siRNA)-MST1 were treated with Tau for 48 h. Apoptosis was detected by flow cytometry, and the levels of MST1 and JNK were detected by western blotting. Compared with the control group, 80 mM Tau could significantly induce apoptosis of CRC cells, and the apoptotic rate increased with increasing Tau concentration (P < 0.01). Meanwhile, the protein levels of MST1 and phosphorylated (p)-JNK in Caco-2 cells increased significantly (P < 0.01). The apoptotic rate of the p-EGFP-MST1 plasmid-transfected cancer cells was significantly higher than that of the control group (P < 0.05); however, the apoptotic rate of the p-EGFP-MST1+Tau group was increased further (P < 0.01). Silencing the MST1 gene could decrease the apoptotic rate of cancer cells, and Tau treatment could reverse this decrease. Blocking the JNK signaling pathway significantly reduced the Tau-induced apoptotic rate of CRC cells. Thus, the MST1-JNK pathway plays an important role in Tau-induced apoptosis of CRC cells.

High Glucose‐Induced ROS Production Stimulates Proliferation of Pancreatic Cancer via Inactivating the JNK Pathway

“…JNK is mainly localized in the cytoplasm. When activated, partially activated JNK translocating into the nucleus activates intranuclear transcription factors, such as c-Jun, ATF2, and p53, by phosphorylation [28–30], thus enhancing the expression of downstream apoptosis-related genes and promoting apoptosis [20, 49]. In this study, our results reveal that treatment with high glucose resulted in a marked reduction of p-JNK.…”

Elevated SH3BP5 Correlates with Poor Outcome and Contributes to the Growth of Acute Myeloid Leukemia Cells

“…On the one hand, JNK contributes to cancer cell apoptosis. JNK signaling plays crucial roles in taurine-induced apoptosis of colorectal cancer cells [20]. Further, endoplasmic reticulum stress induced interaction of JNK with mitochondrial SH3BP5, leading to impaired respiration and increased mitochondrial ROS, sustaining JNK activation culminating in apoptosis [8].…”

Role of taurine, its haloamines and its lncRNA TUG1 in both inflammation and cancer progression. On the road to therapeutics? (Review)

“…Focusing on the molecular mechanisms of taurine in more depth, taurine suppressed p53 -/tumor cells more efficiently than p53 +/+ tumor cells, indicating that the apoptosis-stimulatory action of taurine is the consequence of not only mitochondrial apoptotic pathway but also of multiple signaling pathways in colon cancer cells. In support, Liu et al (43) have shown that the mammalian sterile 20-like kinase 1-c-Jun N-terminal kinase (MST1-JNK) signaling pathway was essential for taurine-induced apoptosis in colon cancer cells (Caco-2 and SW620 cells). Following the treatment of colon cancer cells with taurine, the JNK signaling cascade was activated, either by transmitting direct signals to the MST1 target gene or by controlling the action of MST1 target via a feedback mechanism, with the ultimate aim of inducing apoptosis (43).…”

“…In support, Liu et al (43) have shown that the mammalian sterile 20-like kinase 1-c-Jun N-terminal kinase (MST1-JNK) signaling pathway was essential for taurine-induced apoptosis in colon cancer cells (Caco-2 and SW620 cells). Following the treatment of colon cancer cells with taurine, the JNK signaling cascade was activated, either by transmitting direct signals to the MST1 target gene or by controlling the action of MST1 target via a feedback mechanism, with the ultimate aim of inducing apoptosis (43). Importantly, the growth-inhibitory effect of taurine was also proved either in colitis-model induced by TNBS (16) or in another colitis-inducible model caused by DSS (24).…”

“…Taurine functions as a redox-directed agent to specifically target tumor cells, raising the possibilities to achieve drug selectivity without off-target toxicity. Several cases have proved that taurine displays strong growth-inhibitory effect on multiple cancer types including colon cancer ( 42 , 43 ), lung cancer ( 44 ), hepatocarcinoma ( 30 ), pancreatic cancer ( 45 ), glioma ( 46 ), melanoma ( 47 ) breast cancer ( 48 - 51 ), nasopharyngeal carcinoma (NPC) ( 52 ), prostate cancer ( 53 , 54 ) and ovarian cancer ( 55 , 56 ).…”