Effects of combination chemotherapy with biscoclaurine-derived alkaloid (Cepharanthine) and nimustine hydrochloride on malignant glioma cell lines

Katsuhiko Kono, Jun A. Takahashi, Tetsuya Ueba, Hisae Mori, Nobuo Hashimoto, Manabu Fukumoto

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

In the treatment of malignant glioma, chemotherapy plays a critical role as do surgical resection and irradiation. Cepharanthine (CEP), a biscoclaurine-derived alkaloid, reportedly potentiates the effects of antitumor agents and induces apoptosis in some cancer cells. Here, we examined the effects of CEP, alone and in combination with nimustine hydrochloride (ACNU), on the in vitro proliferation of malignant glioma cells. The cell lines used were U87MG, U251MG, and T98G. At concentrations from 1 to 10 μg/ml, CEP-promoted cell proliferation somewhat; growth inhibition was noted at concentrations of 15 μg/ml and higher. Phase-contrast microscopy showed that cells tended to detach from the culture dishes and that cell density became sparse at the higher concentrations. DAPI fluorescence nuclear staining revealed condensation and fragmentation of nuclei, indicating the induction of apoptosis. To examine the cascade of apoptosis, the caspase inhibitors YVAD and DEVD were added. They inhibited CEP-induced apoptosis in U251MG cells (a p53-mutant cell line), but not in U87MG cells (a p53 wild-type cell line), suggesting that in CEP-induced apoptosis two possible cascades are in play. In combination with ACNU, the effects of the higher concentrations of CEP were enhanced.

Original languageEnglish
Pages (from-to)101-108
Number of pages8
JournalJournal of Neuro-Oncology
Volume56
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • Apoptosis
  • Cepharanthine
  • Malignant glioma
  • Nimustine hydrochloride
  • p53

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

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