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Research Paper|Volume 12, Issue 2|pp 1624—1642

TPGS-1000 exhibits potent anticancer activity for hepatocellular carcinoma in vitro and in vivo

Yidan Chen1, Liqin Mo1, Xuan Wang2, Bi Chen3, Yunfen Hua4, Linyan Gong3, Fei Yang3, Yongqiang Li3, Fangfang Chen3, Guiting Zhu3, Wei Ni3, Cheng Zhang3, Yuming Cheng3, Yan Luo3, Junping Shi3, Mengsheng Qiu2, Shixiu Wu1, Zhou Tan2, Kaifeng Wang1,5
  • 1Cancer Research Institute, Hangzhou Cancer Hospital, Zhejiang, China
  • 2Life Sciences Research Institute, College of Life and Environmental Sciences, Hangzhou Normal University, Zhejiang, China
  • 3Oncology Department, The Affiliated Hospital of Hangzhou Normal University, Zhejiang, China
  • 4College of Pharmaceutical Science, Zhejiang University of Technology, Zhejiang, China
  • 5State Key Laboratory for Oncogenes and Related Genes, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Cancer Institute, Shanghai, China
* Equal contribution
Received: January 28, 2019Accepted: January 2, 2020Published: January 27, 2020
https://doi.org/10.18632/aging.102704

Copyright: © 2020 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS1000) is the most active water-soluble derivative of vitamin E and has been widely used as a carrier of solvents, plasticizers, emulsifiers, absorbent agents and refractory drug delivery systems. However, its anti-hepatocellular carcinoma (HCC) properties have not been explored. HCC cells were treated with different concentrations of TPGS1000. Cell survival was tested by CCK8 assay, and cell migration was tested by wound healing and Transwell assay. EdU staining verified cell proliferation, and signalling pathway was assayed by Western blot analysis. The BALB/c-nu mouse xenograft model was established to test HCC cell growth in vivo. In vitro TPGS1000 significantly inhibited the viability and mobility of HCC cells (HepG2, Hep3B and Huh7) in a dose-dependent manner. Cell cycle analysis indicated that TPGS1000 treatment arrested the HCC cell cycle in the G0/G1 phase, and induction of cell apoptosis was confirmed by TUNEL and Annexin V-7-AAD staining. Further pharmacological analysis indicated that collapse of the transmembrane potential of mitochondria, increased ROS generation, PARP-induced cell apoptosis and FoxM1-p21-mediated cell cycle arresting, were involved in the anti-HCC activity of TPGS1000. Moreover, treatment in vivo with TPGS1000 effectively impaired the growth of HCC xenografts in nude mice.