Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line

Abstract

Background: Kinesin spindle proteins (KSP) are motor proteins that play an essential role in mitotic spindle formation. HsEg5, a KSP, is responsible for the formation of the bipolar spindle, which is critical for proper cell division during mitosis. The function of HsEg5 provides a novel target for the manipulation of the cell cycle and the induction of apoptosis. SB715992, an experimental KSP inhibitor, has been shown to perturb bipolar spindle formation, thus making it an excellent candidate for anti-cancer agent. Our major objective was a) to investigate the cell growth inhibitory effects of SB715992 on PC-3 human prostate cancer cell line, b) to investigate whether the growth inhibitory effects of SB715992 could be enhanced when combined with genistein, a naturally occurring isoflavone and, c) to determine gene expression profile to establish molecular mechanism of action of SB715992.

SCH 2047069, a Novel Oral Kinesin Spindle Protein Inhibitor, Shows Single-Agent Antitumor Activity and Enhances the Efficacy of Chemotherapeutics

“…15). In addition, enhanced apoptosis was shown for the KSP inhibitor SB-715992 and genistein (16). Contrary to our findings with SCH 2047069 and paclitaxel, combination studies reported previously with KSP inhibition and paclitaxel are reported to be antagonistic.…”

A polyphenol mixture from cinnamon targets p38 MAP kinase-regulated signaling pathways to produce G2/M arrest

“…Tumor cells that are arrested at a particular cell phase can be eliminated by more effective and less toxic strategies than when growth is completely out of control. Associated toxicities accompanying radiation and chemotherapy modalities have been reduced because of the genistein-induced arrest at the G2/M phase [27,28].…”

Potential new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor

“…Subsequent inhibitors of the ATPase activity of KSP that have been reported include the dihydropyrimidine-2-thione derivative dimethylenastron [7,8], the quinazolinone derivatives ispinesib [9] and SB-743921 [10], the dihydropyrrole derivative MK-0731 [11], the tetrahydroquinoline derivative EMD-534085 [12], the cysteine derivative S-trityl-L-cysteine [13], and a biphenyl derivative [14]. Some of these KSP inhibitors have undergone clinical trials [10,15e21].…”