Michelia compressa-Derived Santamarine Inhibits Oral Cancer Cell Proliferation via Oxidative Stress-Mediated Apoptosis and DNA Damage

  • Pharmaceuticals (Basel). 2024 Feb 9;17(2):230. doi: 10.3390/ph17020230.
Hsin-I Lu  1 ,  Kuan-Liang Chen  2 ,  Ching-Yu Yen  2  3 ,  Chung-Yi Chen  4 ,  Tsu-Ming Chien  5  6 ,  Chih-Wen Shu  7 ,  Yu-Hsuan Chen  8 ,  Jiiang-Huei Jeng  9  10  11 ,  Bing-Hung Chen  12 ,  Hsueh-Wei Chang  1  8  13  14
Affiliations
  • 1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 2. Department of Dentistry, Chi-Mei Medical Center, Tainan 71004, Taiwan.
  • 3. School of Dentistry, Taipei Medical University, Taipei 11031, Taiwan.
  • 4. Department of Nutrition and Health Sciences, School of Medical and Health Sciences, Fooyin University, Kaohsiung 83102, Taiwan.
  • 5. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.
  • 6. Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 7. Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
  • 8. Department of Biomedical Science and Environmental Biology, Bachelor Program of Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 9. School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 10. Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
  • 11. Department of Dentistry, National Taiwan University Hospital, Taipei 100225, Taiwan.
  • 12. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 13. Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 14. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
PMID: 38399445 DOI: 10.3390/ph17020230
Abstract

The anti-oral Cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the Anticancer effects and acting mechanism of SAMA against oral Cancer (OC-2 and HSC-3) in parallel with normal (Smulow-Glickman; S-G) cells. SAMA selectively inhibits oral Cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of Reactive Oxygen Species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral Cancer cells at the G2/M phase. SAMA triggers Apoptosis (annexin V) in oral Cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral Cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these Anticancer mechanisms of SAMA are more highly expressed in oral Cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells.

Keywords
apoptosis; evergreen tree; natural product; oral cancer; oxidative stress.
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