Alpinumisoflavone Impairs Mitochondrial Respiration via Oxidative Stress and MAPK/PI3K Regulation in Hepatocellular Carcinoma Cells

Hyewon Jang, Jiyeon Ham, Jisoo Song, Gwonhwa Song, Whasun Lim

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Alpinumisoflavone is a natural prenylated isoflavonoid extracted from the raw fruit of Cudrania tricuspidata. Several studies have reported the beneficial characteristics of alpinumisoflavone, such as its antioxidant, anti-inflammation, anti-bacterial, osteoprotective, and neuroprotective effects. Alpinumisoflavone also has anti-cancer effects on thyroid, renal, and ovarian cancers, but its therapeutic effects on hepatocellular carcinoma (HCC) have not yet been demonstrated. We investigated the anti-cancer effects of alpinumisoflavone on HCC using human liver cancer cell lines, Hep3B and Huh7. Our results confirmed that alpinumisoflavone inhibited viability and regulated the MAPK/PI3K pathway in Hep3B and Huh7 cells. We also verified that alpinumisoflavone can depolarize the mitochondrial membrane potential and suppress the mitochondrial respiration in HCC cells. Moreover, we confirmed the dysregulation of the mitochondrial complexes I, III, and V involving mitochondrial oxidative phosphorylation at the mRNA level and the accumulation of calcium ions in the mitochondrial matrix. Lastly, we demonstrated that alpinumisoflavone induced mitochondria-mediated apoptosis via regulation of the Bcl-xL and BAK proteins. This study elucidates the anti-cancer effects of alpinumisoflavone on HCC.

Original languageEnglish
Article number1929
JournalAntioxidants
Volume11
Issue number10
DOIs
Publication statusPublished - 2022 Oct

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (grant numbers: 2021R1A2C2005841 and 2021R1C1C1009807). This research was also supported by Sungkyunkwan University and the BK21 FOUR (Graduate School Innovation) funded by the Ministry of Education (MOE, Korea) and the National Research Foundation of Korea (NRF).

Publisher Copyright:
© 2022 by the authors.

Keywords

  • OXPHOS
  • alpinumisoflavone
  • calcium homeostasis
  • liver cancer
  • oxidative stress

ASJC Scopus subject areas

  • Food Science
  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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