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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)1221-1234
Number of pages14
JournalEnvironmental Toxicology
Volume39
Issue number3
DOIs
Publication statusPublished - Mar 2024

Keywords

  • alkaloid
  • indole-naphthoquinone
  • Murraya paniculata
  • oral cancer
  • oxidative stress

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

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