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Potent antitumor activity of cepharanthine against triple-negative breast cancer spheroids compared with tetrandrine

  • Kiyomi, Anna1
  • Miyakawa, Risako1
  • Matsumoto, Juri1
  • Yamazaki, Kyousuke1
  • Imai, Shinobu1
  • Yuan, Bo2
  • Hirano, Toshihiko3
  • Sugiura, Munetoshi1
  • 1 Department of Drug Safety and Risk Management, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan
  • 2 Laboratory of Pharmacology, School of Pharmacy, Josai University, Sakado, Saitama 350-0295, Japan
  • 3 Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan
Published Article
Oncology Letters
Spandidos Publications
Publication Date
Oct 06, 2020
DOI: 10.3892/ol.2020.12191
PMID: 33101499
PMCID: PMC7577078
PubMed Central


Cepharanthine (CEP) is a bis-bynzelisoquinoline alkaloid from the same class as the anticancer agent tetrandrine (TET). However, the effects of CEP against breast cancer have not been extensively studied, despite its long therapeutic history with low toxicity against other types of cancer. 3D culture systems more accurately mimic the human body and address the limitations of determining drug effectiveness compared with 2D culture systems. In the present study, the antitumor activities of TET and CEP were compared in 3D culture systems in triple-negative breast cancer (TNBC) MDA-MB-231 and estrogen receptor-positive breast cancer MCF-7 cell lines. Cell viability, apoptosis and cytotoxicity assays were performed to determine the total number of live or dead cells, the IC50 values, the number of apoptotic cells and spheroid roundness. Viability suppression of MDA-MB-231 cells was significantly greater with both TET and CEP compared with that of MCF-7 cells, and the roundness of MDA-MB-231 spheroids treated with CEP was decreased significantly compared with that of spheroid treated with TET. Cytoplasmic shrinkage in each cell line significantly increased with the treatment of TET compared with the control; however, this effect was stronger with CEP. The ratio of dead/live cells in each cell line treated with TET and CEP increased in a dose-dependent manner. Overall, the present study demonstrated that CEP had greater cell toxicity in 3D spheroids of breast cancer cells compared with TET, suggesting that CEP may have a stronger antitumor activity on TNBC spheroids compared with TET.

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