Baohuoside-1 targeting mTOR inducing apoptsis to inhibit hepatocellular carcinoma proliferation, invasion and migration

Biomed Pharmacother. 2020 Aug:128:110366. doi: 10.1016/j.biopha.2020.110366. Epub 2020 Jun 8.

Abstract

Background: Baohuoside-1 is a flavonoid compound isolated from Epimedium koreanum Nakai. This study tried to systematically explore the potential anti-cancer functions of Baohuoside-1 in Hepatocellular Carcinoma and study related molecular mechanism. Moreover, as a potential candidate anti-cancer agent, Baohuoside-1 has relatively low toxic side effect.

Methods: The anti-cancer function including proliferation, invasion and migration of Baohuoside-1 in liver cancer was systematically assessed via colony formation, transwell assay and migration assay. Moreover, the anti-cancer functions of Baohuoside-1 was confirmed based on the nude mouse transplantation tumor experiment. The potential targeted signaling pathway was tested via flow cytometery and western blot analysis.

Results: In this study, we present the anti-HCC activity of Baohuoside-1 isolated from Epimedium through examing the effect of Baohuoside-1 on two different human liver cancer cell lines (HuH-7 and HepG2). Baohuoside-1 significantly inhibited the proliferation, invasion and migration of two liver cancer cell lines. Furthermore, the anticancer activity of Baohuoside-1 was confirmed via inhibiting liver tumor growth in nude mice in vivo. Additionally, the influence of Baohuoside-1 on liver cancer apoptosis was examined by analyzing the expression of pro/anti-apoptotic proteins (BAX, Bcl-2, caspase-3, and caspase-8). The potential targeting signaling of Baohuoside-1 was determined via testing key members' expression changes of mTOR and JAK2 signaling.

Conclusion: The inhibition of liver cancer by Baohuoside-1 is through targeting mTOR signaling not JAK2 signaling to induce apoptosis. Our study indicates that Baohuoside-1 is a potential candidate drug for therapy against liver cancer.

Keywords: Apoptsis; Baohuoside-1; Hepatocellular carcinoma.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Flavonoids / pharmacology*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • Flavonoids
  • baohuoside I
  • MTOR protein, human
  • TOR Serine-Threonine Kinases