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Jolkinolide B induces neuroendocrine differentiation of human prostate LNCaP cancer cell line

Euphorbia fischeriana is a Chinese herbal medicine which has been reported to possess chemotherapeutic effects, yet the underlying mechanism is unclear. In order to understand its possible anti-tumor property, we have isolated a number of chemical compounds from the roots of this plant [Phytochemist...

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Published in:Biochemical pharmacology 2002-03, Vol.63 (5), p.951-957
Main Authors: Liu, W.K., Ho, J.C.K., Qin, Guowei, Che, Chun-Tao
Format: Article
Language:English
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Summary:Euphorbia fischeriana is a Chinese herbal medicine which has been reported to possess chemotherapeutic effects, yet the underlying mechanism is unclear. In order to understand its possible anti-tumor property, we have isolated a number of chemical compounds from the roots of this plant [Phytochemistry 52 (1999) 117] and studied their in vitro effects by using human prostate LNCaP cancer cell line. Among the six compounds tested, jolkinolide B exhibited the most potent anti-proliferative activity ( ic 50=12.5 μg/mL=40 μM) and it inhibited DNA synthesis by down-regulating bromodeoxyuridine (BrdU) incorporation in LNCaP cells in a dose-dependent manner. Jolkinolide B, at concentrations up to 25 μg/mL, induced G1 arrest and neuroendocrine differentiation of LNCaP cells. Immunoblotting analysis confirmed the increased expression of neuroendocrine markers, keratin 8/18 (K8/18) and neuron specific enolase (NSE), in these cells. Apoptotic bodies and DNA fragmentation were observed by fluorescence microscopy and flow cytometry when the cells were exposed to a concentration higher than 25 μg/mL jolkinolide B. Taken all data together, jolkinolide B seems to play a role in the regulation of proliferation, differentiation, and apoptosis of LNCaP cells.
ISSN:0006-2952
1873-2968
DOI:10.1016/S0006-2952(01)00938-8