Different docetaxel-induced apoptotic pathways are present in prostate cancer cell lines LNCaP and PC-3.

OBJECTIVES

To investigate the molecular machinery of docetaxel (Taxotere)-initiated death signaling on prostate cancer cell lines LNCaP and PC-3. Taxotere is a member of the taxane family of chemotherapeutic agents. It has been shown to disrupt microtubule dynamics causing mitotic arrest, which leads to cell death. Taxotere has demonstrated induction of cell death in LNCaP and PC-3 cells. However, the pathways by which apoptosis occurs differ in each cell line.

METHODS

The prostate cancer cell lines, LNCaP and PC-3, were treated with 40 nM Taxotere for various lengths of time (0.5 to 24 hours). Western blot analysis was used for protein analysis.

RESULTS

LNCaP cells demonstrated caspase-3 and caspase-7 cleavage, and PC-3 cells demonstrated only caspase-8 and BH3-interacting domain death agonist cleavage. Only LNCaP cells were observed to express clusterin expression; PC-3 cells expressed a novel apoptosis inhibitor, survivin.

CONCLUSIONS

In this study, we demonstrated two distinctly different Taxotere-induced apoptotic pathways in LNCaP and PC-3 cells that may be of clinical importance when treating prostate cancer.