Tubeimoside-1 induces oxidative stress-mediated apoptosis and G0/G1 phase arrest in human prostate carcinoma cells in vitro

Abstract

Aim: Tubeimoside-1 (TBMS1), a triterpenoid saponin extracted from the Chinese herbal medicine Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), has shown anticancer activities in various cancer cell lines. The aim of this study was to investigate the anticancer activity and molecular targets of TBMS1 in human prostate cancer cells in vitro. Methods: DU145 and P3 human prostate cancer cells were treated with TBMS1. Cell viability and apoptosis were detected. ROS generation, mitochondrial membrane potential and cell cycle profile were examined. Western blotting was used to measure the expression of relevant proteins in the cells. Results: TBMS1 (5-100 μmol/L) significantly suppressed the viability of DU145 and P3 cells with IC 50 values of approximately 10 and 20 μmol/L, respectively. Furthermore, TBMS1 dose-dependently induced apoptosis and cell cycle arrest at G 0 /G 1 phase in DU145 and P3 cells. In DU145 cells, TBMS1 induced mitochondrial apoptosis, evidenced by ROS generation, mitochondrial dysfunction, endoplasmic reticulum stress, modulated Bcl-2 family protein and cleaved caspase-3, and activated ASK-1 and its downstream targets p38 and JNK. The G 0 /G 1 phase arrest was linked to increased expression of p53 and p21 and decreased expression of cyclin E and cdk2. Co-treatment with Z-VAD-FMK (pan-caspase inhibitor) could attenuate TBMS1-induced apoptosis but did not prevent G 0 /G 1 arrest. Moreover, co-treatment with NAC (ROS scavenger), SB203580 (p38 inhibitor), SP600125 (JNK inhibitor) or salubrinal (ER stress inhibitor) significantly attenuated TBMS1-induced apoptosis. Conclusion: TBMS1 induces oxidative stress-mediated apoptosis in DU145 human prostate cancer cells in vitro via the mitochondrial pathway.

Inhibitory effects of tubeimoside I on synoviocytes and collagen‐induced arthritis in rats

“…In recent decades, the primary pharmacological findings of TBMS I were to demonstrate its potent anti-cancer activity (Chen et al, 2012(Chen et al, , 2016Gu et al, 2016;Lin et al, 2014Lin et al, , 2016Yang et al, 2016). In this study, we demonstrated, for the first time, that TBMS I could effectively prevent arthritis progression and decrease severity of FLSs play a critical role in RA pathogenesis by producing cytokines that perpetuate inflammation and proteases that contribute to cartilage destruction.…”

“…Franquet (Cucurbitaceae), has been demonstrated to possess antiviral, anti‐inflammatory and antivenom effects (Wu et al, ; Yu, Ma, & Jiang, ; Yu, Ma, & Yu, ). In addition, a growing body of evidence indicates that TBMS I has significant antitumor effects, such as inhibiting the cell proliferation, arresting the cell cycle and promoting the cell apoptosis (Chen et al, ; Gu et al, ; Lin et al, , ; Yang et al, ). Given the known antitumor effects of TBMS I and the similar features observed between cancer cells and activated FLS, we hypothesized that TBMS I may exert a therapeutic effect on RA through attenuating the destructive phenotypes of activated FLS.…”

Research progress on therapeutic targeting of quiescent cancer cells

“…Itraconazole treatment initially caused a proliferative burst, forcing dormant cells to cycle briefly and subsequently enter irreversible G1 cell cycle arrest and senescence [31,48]. Furthermore, tubeimoside-1 potently suppressed the growth of human prostate cancer cells via inducing oxidative stress-mediated apoptosis and G0/G1 phase arrest [49]. Arctigenin, the active component of burdock root, enhanced p27 Kip1 protein levels through inhibition of Akt and stimulation of FOXO3a activity, in turn, suppressing CDK2 kinase activity and finally inducing overall inhibition of HSC proliferation and G0/G1 phase arrest [50].…”

Development of Certain Protein Kinase Inhibitors with the Components from Traditional Chinese Medicine

“…Tubeimoside-1 inhibited the growth of several cancer cells including gliomas, lung cancer and liver cancer (Zhang et al, 2011; Wang et al, 2011a; Jia et al, 2015). Tubeimoside-1 induced phosphorylation of apoptosis signal-regulating kinase 1 (ASK-1) and its downstream target proteins JNK and p38 in a dose-dependent manner, leading to mitochondrial apoptosis in DU145 human prostate cancer cells (Yang et al, 2016). Activation of MAPK-JNK signaling pathway plays an important role in tubeimoside-1 induced cell cycle arrest in lung cancer cells (Hao et al, 2015).…”