Ya-Min Shi1, Lei Yang1, Ya-Di Geng1, Chao Zhang1, Ling-Yi Kong2. 1. State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. 2. State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: cpu_lykong@126.com.
Abstract
BACKGROUND: Polyphyllin I (PPI), a bioactive phytochemical isolated from the rhizoma of Paris polyphyllin, exerts preclinical anticancer efficacy in various cancer models. However, the effects of PPI on regulatory human hepatocellular carcinoma (HCC) cell proliferation and its underlying mechanisms remain unknown. PURPOSE: This study investigated the antiproliferation effect of PPI on HCC cells and its underlying mechanisms. METHODS: Cell viability was measured by MTT assay. Cell death, apoptosis and acidic vesicular organelles (AVOs) formation were determined by flow cytometry. Protein levels were analyzed by Western blot analysis. RESULTS: PPI induced apoptosis through the caspase-dependent pathway and activated autophagy through the PI3K/AKT/mTOR pathway. Blockade of autophagy by pharmacological inhibitors or RNA interference enhanced the cytotoxicity and antiproliferation effects of PPI. Moreover, chloroquine (CQ) enhanced the antiproliferation effect of PPI on HCC cells via the caspase-dependent apoptosis pathway by inhibiting protective autophagy. Therefore, the combination therapy of CQ and PPI exhibited synergistic effects on HCC cells compared with CQ or PPI alone. CONCLUSION: The current findings strongly indicate that PPI can induce protective autophagy in HCC cells, thereby providing a novel target in potentiating the anticancer effects of PPI and other chemotherapeutic drugs in liver cancer treatment. Moreover, the combination therapy of CQ and PPI is an effective and promising candidate to be further developed as therapeutic agents in the treatment of liver cancer.
BACKGROUND:Polyphyllin I (PPI), a bioactive phytochemical isolated from the rhizoma of Paris polyphyllin, exerts preclinical anticancer efficacy in various cancer models. However, the effects of PPI on regulatory humanhepatocellular carcinoma (HCC) cell proliferation and its underlying mechanisms remain unknown. PURPOSE: This study investigated the antiproliferation effect of PPI on HCC cells and its underlying mechanisms. METHODS: Cell viability was measured by MTT assay. Cell death, apoptosis and acidic vesicular organelles (AVOs) formation were determined by flow cytometry. Protein levels were analyzed by Western blot analysis. RESULTS:PPI induced apoptosis through the caspase-dependent pathway and activated autophagy through the PI3K/AKT/mTOR pathway. Blockade of autophagy by pharmacological inhibitors or RNA interference enhanced the cytotoxicity and antiproliferation effects of PPI. Moreover, chloroquine (CQ) enhanced the antiproliferation effect of PPI on HCC cells via the caspase-dependent apoptosis pathway by inhibiting protective autophagy. Therefore, the combination therapy of CQ and PPI exhibited synergistic effects on HCC cells compared with CQ or PPI alone. CONCLUSION: The current findings strongly indicate that PPI can induce protective autophagy in HCC cells, thereby providing a novel target in potentiating the anticancer effects of PPI and other chemotherapeutic drugs in liver cancer treatment. Moreover, the combination therapy of CQ and PPI is an effective and promising candidate to be further developed as therapeutic agents in the treatment of liver cancer.
Authors: Ying Huang; Huacui Xiong; Ke Chen; Xiaobin Zhu; Xiaoping Yin; Yun Liang; Wei Luo; Qiyin Lei Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2019-01-30