Physcion 8-O-β-glucopyranoside inhibits clear-cell renal cell carcinoma bydownregulating hexokinase II and inhibiting glycolysis

Publication date: August 2018
Source:Biomedicine & Pharmacotherapy, Volume 104
Author(s): Qiang Wang, Yi Yan, Jie Zhang, Peng Guo, Yuqing Xing, Yong Wang, Fawei Qin, Qingyun Zeng
BackgroundClear-cell renal cell carcinoma (ccRCC) has the highest prevalence, approximately 80%, amongst all RCC cases. Therefore, the development of novel therapeutic agents against ccRCC is imperative. Our previous studies have shown that physcion 8-O-β-glucopyranoside (PG), an anthraquinone extracted from Rumexjaponicus Houtt, exerted an anti-cancer effect in hepatocellular carcinoma cells. The present study was aimed to investigate a possible anti-neoplastic role of PG in ccRCC and the relevant underlying mechanism.Materials and methodsTwo human ccRCC cell lines- RCC4 and ACHN- were used as in vitro models and treated with varying concentrations of PG. Cell Counting Kit-8 (CCK-8) assay was used to determine cell viability, and Annexin-V FITC/PI staining was used to analyze the percentage of apoptotic cells after PG treatment. Commercially available kits were used to measure the rates of glucose consumption and lactate production. Changes in mitochondrial membrane potential were examined by flow cytometry, and western blotting was performed to analyze the levels of various apoptosis markers. To examine the role of HK2 in the anti-tumor effect of PG, ccRCC cells were transfected with a vector overexpressing HK2. Moreover, a xenograft model was established to evaluate the therapeutic effect of PG in vivo.ResultsPG decreased viability in dose-dependent manner and induced apoptosis via the intrinsic pathway, along with inhibiting glycolysis in the ccRCC cell lines. Mechanistically, PG induced apoptosis and suppressed glycolysis by downregulating HK2. In vivo data also demonstrated that PG could exert an anti-tumor activity without any adverse side-effects.ConclusionPG induced mitochondrial apoptosis and inhibited glycolysis in clear-cell renal cell carcinoma. Our findings provide preliminary experimental data that support further investigation of the therapeutic efficacy of PG in ccRCC.



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