Pyrogallol induces G0/G1 cell cycle arrest and apoptosis through mitochondrial pathway in PC-3 human prostate cancer cells
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Pyrogallol (PG), a naturally occurring dihydroxyphenol, was shown to suppress the proliferation of numerous cancer cell lines (e.g., lymphoma, lung, and breast cancer cells). However, its effects on human prostate cancer remain largely unexplored. Thus, we evaluated the anti-cancer effects of PG in prostate cancer cells (i.e., PC-3, RC-58T, and LNCaP) and a xenograft mouse model. In the in vitro assays, cells were treated with PG at various concentrations (2.5-200 μM) for 1 day, and the half-maximal inhibitory concentration (IC50) values were determined to be 55.53 μM for PC-3, 65.03 μM for RC-58T, 71.78 μM for LNCaP, and >200 μM for RWPE-1. Mechanistic analyses on PC-3 cell lines revealed that PG induced mitochondrial-dependent apoptosis, as evidenced by increased expression of apoptosis signaling (i.e., Bax, cytochrome C, caspase-3, and PARP), and decreased expression of anti-apoptosis signaling as Bcl-2. Additionally, PG modulated MAPK pathways, which were associated with the activation of caspase-3 and caspase-8. Furthermore, PG treatment induced G0/G1 phase cell cycle arrest. In our in vivo model, groups treated with PG (2.5-5 mg/kg, p.o.) for 2 weeks exhibited a significant reduction in tumor growth, along with increased expression of apoptotic signaling markers in tumor tissues. We suggest that PG may serve as a promising therapeutic agents for prostate cancer, highlighting their potential applications in phytomedicine and phytotherapy.
Abstract
Pyrogallol (PG), a naturally occurring dihydroxyphenol, was shown to suppress the proliferation of numerous cancer cell lines (e.g., lymphoma, lung, and breast cancer cells). However, its effects on human prostate cancer remain largely unexplored. Thus, we evaluated the anti-cancer effects of PG in prostate cancer cells (i.e., PC-3, RC-58T, and LNCaP) and a xenograft mouse model. In the in vitro assays, cells were treated with PG at various concentrations (2.5-200 μM) for 1 day, and the half-maximal inhibitory concentration (IC50) values were determined to be 55.53 μM for PC-3, 65.03 μM for RC-58T, 71.78 μM for LNCaP, and >200 μM for RWPE-1. Mechanistic analyses on PC-3 cell lines revealed that PG induced mitochondrial-dependent apoptosis, as evidenced by increased expression of apoptosis signaling (i.e., Bax, cytochrome C, caspase-3, and PARP), and decreased expression of anti-apoptosis signaling as Bcl-2. Additionally, PG modulated MAPK pathways, which were associated with the activation of caspase-3 and caspase-8. Furthermore, PG treatment induced G0/G1 phase cell cycle arrest. In our in vivo model, groups treated with PG (2.5-5 mg/kg, p.o.) for 2 weeks exhibited a significant reduction in tumor growth, along with increased expression of apoptotic signaling markers in tumor tissues. We suggest that PG may serve as a promising therapeutic agents for prostate cancer, highlighting their potential applications in phytomedicine and phytotherapy.