Title:Mitosis-Targeting Natural Products for Cancer Prevention and Therapy
Volume: 13
Issue: 14
Author(s): Chinthalapally V. Rao, Carla D. Kurkjian and Hiroshi Y. Yamada
Affiliation:
Keywords:
Natural product, taxol, mitosis, spindle microtubule, kinesin, spindle checkpoint, proteasome, anaphase promoting
complex/cyclosome, cyclin/CDK complex
Abstract: Mitosis is a complex process resulting in division of a cell into two daughter cells, and its failure often results
in the death of the daughter cells (via apoptotic, necrotic, or proliferative/senescent death). Many chemicals that inhibit the
mitotic process (anti-mitotic drugs) have proven effective for killing cancer cells in vitro and in clinical settings. Among
the most studied anti-mitotic drugs are plant-origin natural products including taxanes (e.g. paclitaxel, docetaxel) and
vinca alkaloids (e.g. vincristine, vinblastine), whose validated target is the spindle microtubules. With the success of these
agents, efforts have been made to develop other spindle poisons as well as to improve efficacy of existing spindle poisons
with structural modifications. Novel drugs and natural products that inhibit other proteins involved in mitosis (nonmicrotubule
targets) have been sought in hopes of expanding available cancer-directed therapies. Recently, significant advances
have been made in the understanding of mitotic mechanisms in tumor cells as well as in normal epithelial cells.
These advances help us to identify and develop potential natural agents for the prevention and treatment of cancer. This
review will focus on natural products that target mitotic process and/or proteins involved in mitotic progression.
