Selective Protection of Normal Proliferationg Cells Against Anti-Neoplastic Chemotherapy by Stausporine Pretreatment

Jung, Sang Hee; Kwon, Moon Ki; Jo, Yoon Sung; Song, Min Kyung; Ryu, Ki Sung; Rha, Jong Gu; Han, Ku Taek

Abstract

OBJECTIVE
A major limiting factor in human cancer chemotherapy is toxicity in normal cells and tissues. Our goal was to determine whether normal proliferating cells could be protected from chemotherapeutic agents by taking advantage of the differential drug sensitivity of cell cycle G1 checkpoint in normal and cancer cells.
METHODS
Normal peripheral blood mononuclear cells (PBMC) and ovarian cancer cell lines (OVCAR- 3 and SKOV-3) were initially treated with 10 nM of staurosporine for 48 hours. After removal of staurosporine contained media, both PBMC and ovarian cancer cells were treated with 20 nM of paclitaxel for 24 hours. Cells were then allowed to recover in drug-free medium for 4 days. The DNA contents and cell cycle changes were detected by FACScan flow cytometer in the cells harvested whenever the medium was changed.
RESULTS
After pretreatment of ovarian cancer cell lines (OVCAR-3 and SKOV-3) with 10 nM of staurosporine followed by treatment with 20 nM of paclitaxel, both OVCAR-3 and SKOV-3 cells were selectively arrested in G2M phase of cell cycle by paclitaxel and they resumed their proliferative cycle to some extents after the drugs were removed and cultured with fresh media. However. pretreatment with 10 nM of staurosporine protected normal circulating PBMC that had been induced to proliferate in vitro with phytohemagglutinin from paclitaxel. Staurosporine-induced arrest of PBMC in G0/G1 phase was reversible, and arrested cells tolerated 10 nM of paclitaxel in culture.
CONCLUSION
OVCAR-3 and SKOV-3 cancer cells can be targeted specifically with paclitaxel, following staurosporine-mediated, selective and reversible G0/G1 arrest in PBMC.