Magnolia extract is effective for the chemoprevention of oral cancer through its ability to inhibit mitochondrial respiration at complex i

Qi Zhang, Gang Cheng, Jing Pan, Jacek Zielonka, Donghai Xiong, Charles R. Myers, Liang Feng, Song Seok Shin, Young Heui Kim, Dinh Bui, Ming Hu, Brian Bennett, Kathleen Schmainda, Yian Wang, Balaraman Kalyanaraman, Ming You

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background: Magnolia extract (ME) is known to inhibit cancer growth and metastasis in several cell types in vitro and in animal models. However, there is no detailed study on the preventive efficacy of ME for oral cancer, and the key components in ME and their exact mechanisms of action are not clear. The overall goal of this study is to characterize ME preclinically as a potent oral cancer chemopreventive agent and to determine the key components and their molecular mechanism(s) that underlie its chemopreventive efficacy. Methods: The antitumor efficacy of ME in oral cancer was investigated in a 4-nitroquinoline-1-oxide (4NQO)-induced mouse model and in two oral cancer orthotopic models. The effects of ME on mitochondrial electron transport chain activity and ROS production in mouse oral tumors was also investigated. Results: ME did not cause detectable side effects indicating that it is a promising and safe chemopreventive agent for oral cancer. Three major key active compounds in ME (honokiol, magnolol and 4-O-methylhonokiol) contribute to its chemopreventive effects. ME inhibits mitochondrial respiration at complex I of the electron transport chain, oxidizes peroxiredoxins, activates AMPK, and inhibits STAT3 phosphorylation, resulting in inhibition of the growth and proliferation of oral cancer cells. Conclusion: Our data using highly relevant preclinical oral cancer models, which share histopathological features seen in human oral carcinogenesis, suggest a novel signaling and regulatory role for mitochondria-generated superoxide and hydrogen peroxide in suppressing oral cancer cell proliferation, progression, and metastasis. [MediaObject not available: see fulltext.]

Original languageEnglish (US)
Article number58
JournalCell Communication and Signaling
Volume18
Issue number1
DOIs
StatePublished - Apr 7 2020

Keywords

  • AMPK
  • Complex I
  • Oral cancer
  • STAT3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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