Alphitolic acid, an anti-inflammatory triterpene, induces apoptosis and autophagy in oral squamous cell carcinoma cells, in part, through a p53-dependent pathway

Li Yuan Bai, Chang Fang Chiu, Shih Jiuan Chiu, Yu Wen Chen, Jing Lan Hu, Chia Yung Wu, Jing Ru Weng

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The antitumour mechanism of alphitolic acid (ALA), an anti-inflammatory triterpene, in oral squamous cell carcinoma (OSCC) cells was investigated. ALA suppressed the proliferation of SCC4 and SCC2095 OSCC cells with IC50 values of 12 and 15 μM, respectively, via apoptotic induction. Mechanistically, this drug effect on apoptosis was, in part, associated with its ability to block Akt-NF-κB signalling. Moreover, ALA induced autophagy, as evidenced by increased expression of the autophagy biomarkers Beclin 1, Atg7, and LC3B-II, and autophagosome formation. This autophagy induction played a protective role as autophagy inhibitors enhanced cellular susceptibility to ALA-induced apoptosis. Also noteworthy is the involvement of p53 in ALA-mediated cytotoxicity. ALA increased p53 phosphorylation/expression, accompanied by parallel decreases in the expression of the oncogenic E3 ligase MDM2, and shRNA-mediated knockdown of p53 partially rescued ALA-mediated cytotoxicity. Together, these findings suggest the translational value of ALA as an ingredient in functional food/dietary supplement for OSCC prevention.

Original languageEnglish
Article number1245
Pages (from-to)368-378
Number of pages11
JournalJournal of Functional Foods
Volume18
DOIs
Publication statusPublished - Oct 1 2015

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Triterpenes
autophagy
Autophagy
squamous cell carcinoma
triterpenoids
Squamous Cell Carcinoma
mouth
Anti-Inflammatory Agents
apoptosis
Apoptosis
Acids
acids
cells
Dietary Supplements
cytotoxicity
acid value
Functional Food
Ubiquitin-Protein Ligases
ligases
functional foods

Keywords

  • Alphitolic acid
  • Apoptosis
  • Autophagy
  • Oral squamous cell carcinoma
  • P53

ASJC Scopus subject areas

  • Food Science
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Alphitolic acid, an anti-inflammatory triterpene, induces apoptosis and autophagy in oral squamous cell carcinoma cells, in part, through a p53-dependent pathway. / Bai, Li Yuan; Chiu, Chang Fang; Chiu, Shih Jiuan; Chen, Yu Wen; Hu, Jing Lan; Wu, Chia Yung; Weng, Jing Ru.

In: Journal of Functional Foods, Vol. 18, 1245, 01.10.2015, p. 368-378.

Research output: Contribution to journalArticle

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abstract = "The antitumour mechanism of alphitolic acid (ALA), an anti-inflammatory triterpene, in oral squamous cell carcinoma (OSCC) cells was investigated. ALA suppressed the proliferation of SCC4 and SCC2095 OSCC cells with IC50 values of 12 and 15 μM, respectively, via apoptotic induction. Mechanistically, this drug effect on apoptosis was, in part, associated with its ability to block Akt-NF-κB signalling. Moreover, ALA induced autophagy, as evidenced by increased expression of the autophagy biomarkers Beclin 1, Atg7, and LC3B-II, and autophagosome formation. This autophagy induction played a protective role as autophagy inhibitors enhanced cellular susceptibility to ALA-induced apoptosis. Also noteworthy is the involvement of p53 in ALA-mediated cytotoxicity. ALA increased p53 phosphorylation/expression, accompanied by parallel decreases in the expression of the oncogenic E3 ligase MDM2, and shRNA-mediated knockdown of p53 partially rescued ALA-mediated cytotoxicity. Together, these findings suggest the translational value of ALA as an ingredient in functional food/dietary supplement for OSCC prevention.",
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