Biomedicine & Pharmacotherapy (Jun 2023)

Total alkaloids in Stephania tetrandra induce apoptosis by regulating BBC3 in human non–small cell lung cancer cells

  • Bichen Li,
  • Juan Chen,
  • Jia He,
  • Jing Peng,
  • Yuxin Wang,
  • Shao Liu,
  • Yueping Jiang

Journal volume & issue
Vol. 162
p. 114635

Abstract

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Purpose: This study investigated the effects of total alkaloids in Stephania tetrandra (TAS) and the main alkaloid components tetrandrine, fangchinoline and cepharanthine on the biological function of lung cancer cells and the mechanism underlying the synergistic antitumor effects of TAS and cisplatin. Methods: RNA sequencing analysis was performed on TAS-treated H1299 cells. Differentially expressed genes were identified and analyzed, and the regulatory pathway was identified by gene set enrichment analysis. The mRNA and protein expression levels of the differentially expressed genes in cells were determined using quantitative reverse transcription–polymerase chain reaction and western blotting, respectively. Cell viability and wound healing assays evaluated the biological function of TAS and the main alkaloid components in non–small cell lung cancer (NSCLC) cells. Flow cytometry was used to determine the apoptosis rate in NSCLC cells. Results: TAS inhibited the proliferation and migration of A549 and H1299 cells and increased the apoptosis rate in a time- and dose-dependent manner. When H1299 cells were treated with TAS (7.5 µg/ml), MGLL and BBC3 were identified as the possible differentially expressed genes. Pathways associated with cisplatin resistance were screened to investigate the effect of TAS on the apoptosis of NSCLC cells. TAS may regulate fatty acid metabolism and induce apoptosis through the upregulated expression of MGLL and BBC3. The combination of TAS at noncytotoxic concentrations (A549: 1.0 μg/ml; H1299: 3.0 μg/ml) and cisplatin significantly inhibited the viability of A549 and H1299 cells. Conclusion: TAS and the main alkaloid components exert anticancer activity in NSCLC by regulating tumor cell proliferation and apoptosis. Therefore, TAS and the main alkaloid components have the potential to be used as multi-targeted drugs for lung cancer treatment.

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