Taxol: Mechanisms of action against cancer, an update with current research

Paclitaxel (Taxol) is a chemo-drug found in the 1960s, which has anti-mitotic effect on cancerous cells and is widely used for various types of cancer like breast, ovarian, lung cancers etc. The mechanisms of action exerted by Taxol will be reviewed in this chapter. Briefly, the principal mechanism of Taxol is its ability to stabilize and prevent microtubules depolymerization, leading to cell cycle arrest at the G2/M phase and cell death. However, this effect could be cell lines and dose dependent. Besides its regulation on mitosis, Taxol also modulates cells survival through apoptotic-regulating proteins, Bcl-2 family and also other signaling pathways like JNK/SAPK, NFκB pathway. Taxol’s activates or inhibits either the pro-apoptotic (BAX/BAK) or anti-apoptotic (Bcl-2/MCL-1) Bcl-2 proteins to cause cell death in the cancer cells. Calcium stored in endoplasmic reticulum also could be attacked by Taxol and be released to disrupt the calcium homeostasis which complicates the cell survival. Taxol was found to exert effects on immune cells, for instance regulatory T cells (Tregs) and macrophages. Taxol has LPS-mimetic effects which allows it to induce Toll-like receptor 4 (TLR4)-dependent signaling pathways to induce apoptosis. Recent studies demonstrated Taxol could reprogram the polarity of macrophages from pro-tumor (M2) type to anti-tumor (M1) phenotype which would boost the immune responses to kill cancer cells.