2. Academic Validation
  3. Polyphyllin I induces autophagy and cell cycle arrest via inhibiting PDK1/Akt/mTOR signal and downregulating cyclin B1 in human gastric carcinoma HGC-27 cells

Polyphyllin I induces autophagy and cell cycle arrest via inhibiting PDK1/Akt/mTOR signal and downregulating cyclin B1 in human gastric carcinoma HGC-27 cells

  • Biomed Pharmacother. 2019 Sep;117:109189. doi: 10.1016/j.biopha.2019.109189.
Junlin He 1,  Si Yu 2,  Chuanjie Guo 1,  Lu Tan 1,  Xiaominting Song 1,  Miao Wang 1,  Jing Wu 1,  Yuling Long 1,  Daoyin Gong 1,  Ruoqi Zhang 1,  Zhixing Cao 1,  Yuzhi Li 3,  Cheng Peng 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu 611137, China.
  • 2 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu 611137, China; Chengdu Medical College, Chengdu 610500, China.
  • 3 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu 611137, China. Electronic address: liyuzhi5654@163.com.
  • 4 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu 611137, China. Electronic address: pengchengchengdu@126.com.
PMID: 31387191 DOI: 10.1016/j.biopha.2019.109189
Abstract

Paris polyphylla. is a traditional medicinal herb that has long been used to prevent Cancer in many Asian countries. Polyphyllin I (PPI), an important bioactive constituent of Paris polyphylla, has been found to exhibit a wide variety of Anticancer activities in many types of Cancer cells. However, the effects of PPI on human gastric carcinoma cells and its mechanism of action remain unclear. In this study, we examined the effective anti-gastric carcinoma activity of PPI and its underlying mechanism of action in HGC-27 cells. In vitro, sub-micromolar concentrations of PPI inhibited HGC-27 cell proliferation with an IC50 of 0.34 ± 0.06 μM after a 72-h treatment. In vivo, 3 mg/kg PPI significantly inhibited proliferation of HGC-27 tumor cells, with a 78.8% inhibition rate compared to paclitaxel, and demonstrated higher safety. Analysis of MDC and mGFP-LC3 fluorescence, Western blotting and flow cytometry indicated that PPI induced cell cycle arrest in HGC-27 cells by promoting the conversion of LC3-I to LC3-II and by downregulating cyclin B1. Furthermore, Western blotting showed that PPI inhibited the autophagy-regulating PDK1/Akt/mTOR signaling pathway in vitro and in vivo. In addition, immunohistochemistry and TUNEL staining revealed that PPI decreased Ki67 expression and increased the percentage of apoptotic cells in HGC-27 xenograft tumors. These data indicate that PPI is an PDK1/Akt/mTOR signaling inhibitor and of therapeutic relevance for gastric Cancer treatment and that the rhizome of Paris polyphylla deserves further clinical investigation as an alternative therapy for gastric Cancer.

Keywords

Autophagy; Cell cycle; Gastric cancer; PDK1/Akt/mTOR; Polyphyllin I.

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