A novel finding: anti-androgen flutamide kills androgen-independent PC-3 cells: aradiolabelled methyl-choline incorporation into tumour cells

摘要

[Methyl-11C]-choline was introduced to image many types of cancers especially thernprostate cancer (1). Al-Saeedi et al. reported that the incorporation of [Methyl-3H]-choline intornbreast tumour (MCF-7) cells correlated strongly with proliferation as determined by [Methyl-14C]-rnthymidine uptake (2). Also, Al-Saeedi et al. (3) showed that the chemotherapy using MCF-7 cellsrntreated with 5-Fluorouracil (5-FU) induced modulation in [Methyl-3H]-choline incorporation andrncertain mechanisms for this modulation were reported. In this study, the androgen-dependentrnprostate tumour (LNCaP) cells were treated with the well known pure anti-androgen drug, flutamide,rnfor 3 days. The cells were then incubated with [Methyl-3H]-choline for 10 minutes to detect therneffect of flutamide on both cell proliferation and choline incorporation. At the same time, arnpreliminary work was established using androgen-independent PC-3 cells treated with flutamide asrncontrols in this study. PC-3 cells were treated with a range of doses of flutamide inhibiting growthrnby 20-70%. Treated and control cells were incubated with [Methyl-3H]-choline for 10 minutes, thenrnin non-radioactive medium to simulate the rapid blood clearance of [Methyl-11C]-choline tracer inrncontrol and treated PC-3 cells, and then extracted with organic and aqueous solvents to determine itsrneffect on the intracellular distribution of this tracer. Results: Interesting results showed thatrnflutamide killed the androgen-independent prostate cancer cells, PC-3 and mechanisms responsiblernfor flutamide-induced modulation on [Methyl-3H]-choline incorporation were reported. The PC-3rncells' proliferation was inhibited by flutamide. In addition, treatment of PC-3 cells with flutamidernfor 3 days resulted in a build up of cells in S phase and [Methyl-3H]-choline incorporation per a cellrnwas found to be decreased in treated compared to untreated cells. Conclusion: flutamide inhibitsrnPC-3 cell proliferation by certain mechanism (unknown) other than the well-known androgenrnreceptor (AR) mechanism, which accordingly induced modulation in [Methyl-3H]-cholinernincorporation into the PC-3 cells.