Effects of combination chemotherapy with biscoclaurine-derived alkaloid (Cepharanthine) and nimustine hydrochloride on malignant glioma cell lines.
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 microg/ml, CEP-promoted cell proliferation somewhat; growth inhibition was noted at concentrations of 15 microg/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.
Kono
Katsuhiko
K
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Japan.
Takahashi
Jun A
JA
Ueba
Tetsuya
T
Mori
Hisae
H
Hashimoto
Nobuo
N
Fukumoto
Manabu
M
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D044182:Benzylisoquinolines; D061945:Caspase Inhibitors; D002455:Cell Division / Q000187:drug effects; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000235:genetics; D016158:Genes, p53; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D015376:Nimustine / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D052117:Benzodioxoles
D000470:Alkaloids; D044182:Benzylisoquinolines; D061945:Caspase Inhibitors; D015376:Nimustine; D009842:Oligopeptides; C108637:aspartyl-glutamyl-valyl-aspartal; C118632:tyrosyl-valyl-alanyl-aspartal; C006947:cepharanthine; D052117:Benzodioxoles