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.