Targeting Microtubules by Phytoestrogens for the Treatment of Cancer: An Overview

Phytoestrogens are naturally occurring compounds that have similar molecular structure to estrogen hence able to exert estrogenic activities by binding to estrogen receptors (ERs), ERα and ERβ. Phytoestrogens have been reported to suppress cancer cell survival and growth in various types of cancers including lung cancer, breast cancer and prostate cancer. Moreover, phytoestrogens have been shown to inhibit cancer cell migration and invasion by targeting multiple pathways. These cellular processes are closely regulated by microtubule cytoskeleton, hence it is interesting to gain more understanding regarding the effects of phytoestrogen on microtubules structure and dynamics. In this review, we summarize reported effects of some phytoestrogens that bind directly to tubulin at various binding site and disrupt the microtubule dynamics, either by promoting microtubule polymerization or enhancing microtubule depolymerization. We also discuss the effects of phytoestrogens in combination with established chemotherapeutic drugs, including the MTAs. Evidence found is crucial for the development of phytoestrogens to be used as monotherapy or combination therapy (as adjuvant).