Ganoderma microsporum immunomodulatory protein induces apoptosis and potentiates mitomycin C‐induced apoptosis in urinary bladder urothelial carcinoma cells

Abstract

Current chemotherapy and immunotherapy treatments followed by transurethral resection for urinary bladder urothelial carcinoma (UC) usually suffer from poor prognosis and high recurrence rate. Design and modification of current formulation with the novel adjuvants are needed. A recombinant protein derived from Ganoderma microsporum named as Ganoderma microsporum immunomodulatory protein (GMIP) was used to treat UC cells. We found GMIP elicits a dose-dependent and time-dependent anti-UC cell proliferation effect, with a half-maximal inhibition concentration (IC ) comparable to mitomycin C (MMC), a commonly used chemotherapy agent. After GMIP treatment, UC cells showed apoptotic phenomenon including cell cycle arrest in the G1 phase, elevated sub-G1 population, mitochondrial membrane potential loss, up-regulated p21 expression, p21 nuclear translocation, caspase activation, and PARP cleavage in a p53-independent but p21-mediated pathways. Unlike lung cancer cells, GMIP treated UC cells showed no autophagic scheme including Beclin-1, an autophagy to apoptosis switch marker, was not cleaved by caspase 3 and slight LC3B-II accumulation. Also, the classic autophagic inhibitor, chloroquine had no effect in GMIP-mediated cell death made us conclude that GMIP induced apoptosis through caspase activation but not autophagy in UC cells. Additionally, GMIP showed synergistic effects with MMC in killing UC cells and thus decreased the concentration of MMC usage to reach the comparable apoptotic effects. Our results delineate novel strategies for treatment of UC by GMIP alone or in combination with MMC application and provide a promising therapeutic cocktail for better treatment of urinary bladder urothelial carcinoma.

Inhibiting TrxR suppresses liver cancer by inducing apoptosis and eliciting potent antitumor immunity

“…Mitochondria serve an important role in the regulation of apoptosis and the mitochondria-mediated apoptosis pathway is accompanied by MMP depolarization, followed by pro-apoptotic molecule release from the mitochondria into the cytosol ( 35 ). In the present study, JC-1 was used as a fluorescent probe, which selectively enters into mitochondria and undergoes a reversible color alteration from green to red as the membrane potential increases.…”

2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile, Exerts Anti-bladder Activities through IGF-1R/STAT3 Signaling

“…SYD007 Arrest of Bladder Cancer Cells Cycle In order to further understand the mechanism of anti-proliferative activity of SYD007, we then used flow cytometry to examine cell cycle progression. It was revealed that SYD007 (5,10,20 and 40 µmol/L, 24 h) induced the accumulation of S and G2/M phase of T24 cells, especially the accumulation of cells in the G2/M phase in dose-dependent manner, accompanied by a decrease in the percentage of cells in the G1 phase, which indicated dominating G2/M phase arrest induced by SYD007 in T24 cells (Fig. 3).…”

“…SYD007 treatment (0.5, 1.25, 2.5, 5.0 and 10.0 µmol/L) for 72 h significantly increased both early and late apoptosis in T24 cells, as compared with vehicle control group (p < 0.01). Previous studies [19][20][21] indicated mitomycin-C (MMC) can significantly induce apoptosis. The effect of pro-apoptosis SYD007 compared with MMC suggest that SYD007 significantly induced early apoptosis on T24.…”

Combination treatment of Src inhibitor Saracatinib with GMI, a Ganoderma microsporum immunomodulatory protein, induce synthetic lethality via autophagy and apoptosis in lung cancer cells

“…Saracatinib (11497) was purchased from Cayman chemical (Ann Arbor, MI). GMI was provided by Mycomagic Biotechnology Co, Ltd. (Taipei, Taiwan), and the generation and extraction of GMI were described previously (Huang et al, 2018).…”