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 [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 microg/mL=40 microM) 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 microg/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 microg/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.
Liu
W K
WK
Department of Anatomy, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Shatin, Hong Kong. ken-liu@cuhk.edu.hk
Ho
J C K
JC
Qin
Guowei
G
Che
Chun Tao
CT
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008856:Microscopy, Fluorescence; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; C057914:jolkinolide B