Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Cis-3-O-p-hydroxycinnamoyl Ursolic Acid Induced ROS-Dependent p53-Mediated Mitochondrial Apoptosis in Oral Cancer Cells

  • Wang, Ching-Ying (Department of Medical Laboratory Science and Biotechnology, China Medical University) ;
  • Lin, Chen-Sheng (Division of Gastroenterology, Kuang Tien General Hospital) ;
  • Hua, Chun-Hung (Department of Otolaryngology, China Medical University Hospital) ;
  • Jou, Yu-Jen (Department of Medical Laboratory Science and Biotechnology, China Medical University) ;
  • Liao, Chi-Ren (Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University) ;
  • Chang, Yuan-Shiun (Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University) ;
  • Wan, Lei (Department of Medical Genetics and Medical Research, China Medical University Hospital) ;
  • Huang, Su-Hua (Department of Biotechnology, Asia University) ;
  • Hour, Mann-Jen (School of Pharmacy, China Medical University) ;
  • Lin, Cheng-Wen (Department of Medical Laboratory Science and Biotechnology, China Medical University)
  • Received : 2017.12.04
  • Accepted : 2018.08.08
  • Published : 2019.01.01
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Abstract

Cis-3-O-p-hydroxycinnamoyl ursolic acid (HCUA), a triterpenoid compound, was purified from Elaeagnus oldhamii Maxim. This traditional medicinal plant has been used for treating rheumatoid arthritis and lung disorders as well as for its anti-inflammation and anticancer activities. This study aimed to investigate the anti-proliferative and apoptotic-inducing activities of HCUA in oral cancer cells. HCUA exhibited anti-proliferative activity in oral cancer cell lines (Ca9-22 and SAS cells), but not in normal oral fibroblasts. The inhibitory concentration of HCUA that resulted in 50% viability was $24.0{\mu}M$ and $17.8{\mu}M$ for Ca9-22 and SAS cells, respectively. Moreover, HCUA increased the number of cells in the sub-G1 arrest phase and apoptosis in a concentration-dependent manner in both oral cancer cell lines, but not in normal oral fibroblasts. Importantly, HCUA induced p53-mediated transcriptional regulation of pro-apoptotic proteins (Bax, Bak, Bim, Noxa, and PUMA), which are associated with mitochondrial apoptosis in oral cancer cells via the loss of mitochondrial membrane potential. HCUA triggered the production of intracellular reactive oxygen species (ROS) that was ascertained to be involved in HCUA-induced apoptosis by the ROS inhibitors YCG063 and N-acetyl-L-cysteine. As a result, HCUA had potential antitumor activity to oral cancer cells through eliciting ROS-dependent and p53-mediated mitochondrial apoptosis. Overall, HCUA could be applicable for the development of anticancer agents against human oral cancer.

Keywords

References

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