Demethoxymurrapanine, an indole-naphthoquinone alkaloid, inhibits the proliferation of oral cancer cells without major side effects on normal cells.

Abstract

Antioral cancer drugs need a greater antiproliferative impact on cancer than on normal cells. Demethoxymurrapanine (DEMU) inhibits proliferation in several cancer cells, but an in-depth investigation was necessary. This study evaluated the proliferation-modulating effects of DEMU, focusing on oral cancer and normal cells. DEMU (0, 2, 3, and 4 μg/mL) at 48 h treatments inhibited the proliferation of oral cancer cells (the cell viability (%) for Ca9-22 cells was 100.0 ± 2.2, 75.4 ± 5.6, 26.0 ± 3.8, and 15.4 ± 1.4, and for CAL 27 cells was 100.0 ± 9.4, 77.2 ± 5.9, 57.4 ± 10.7, and 27.1 ± 1.1) more strongly than that of normal cells (the cell viability (%) for S-G cells was 100.0 ± 6.6, 91.0 ± 4.6, 95.0 ± 2.6, and 95.8 ± 5.5), although this was blocked by the antioxidant N-acetylcysteine. The presence of oxidative stress was evidenced by the increase of reactive oxygen species and mitochondrial superoxide and the downregulation of the cellular antioxidant glutathione in oral cancer cells, but these changes were minor in normal cells. DEMU also caused greater induction of the subG1 phase, extrinsic and intrinsic apoptosis (annexin V and caspases 3, 8, and 9), and DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer than in normal cells. N-acetylcysteine attenuated all these DEMU-induced changes. Together, these data demonstrate the preferential antiproliferative function of DEMU in oral cancer cells, with the preferential induction of oxidative stress, apoptosis, and DNA damage in these cancer cells, and low cytotoxicity toward normal cells.

• Authors: Ya-Ting Chuang, Ching-Yu Yen, Jun-Ping Shiau, Fang-Rong Chang, Chang-Yih Duh, Ping-Jyun Sung, Kuan-Liang Chen, Yi-Hong Tsai, Jen-Yang Tang, Jiiang-Huei Jeng, Jyh-Horng Sheu, Hsueh-Wei Chang
• Journal: Environmental toxicology (Environ Toxicol) Vol. 39 Issue 3 Pg. 1221-1234 (Mar 2024) ISSN: 1522-7278 [Electronic] United States
• PMID: 37921086 (Publication Type: Journal Article)
• Copyright: © 2023 Wiley Periodicals LLC.

Chemical References

• Antioxidants
• Acetylcysteine
• Reactive Oxygen Species
• Alkaloids
• Indoles

Topics

• Humans
• Antioxidants (pharmacology)
• Acetylcysteine (pharmacology)
• Oxidative Stress
• Reactive Oxygen Species
• Mouth Neoplasms (drug therapy)
• Apoptosis
• Cell Proliferation
• Alkaloids (pharmacology, therapeutic use)
• Indoles (pharmacology)
• Cell Line, Tumor
• DNA Damage