How Taxol/paclitaxel kills cancer cells

Abstract

Taxol (generic name paclitaxel) is a microtubule-stabilizing drug that is approved by the Food and Drug Administration for the treatment of ovarian, breast, and lung cancer, as well as Kaposi's sarcoma. It is used off-label to treat gastroesophageal, endometrial, cervical, prostate, and head and neck cancers, in addition to sarcoma, lymphoma, and leukemia. Paclitaxel has long been recognized to induce mitotic arrest, which leads to cell death in a subset of the arrested population. However, recent evidence demonstrates that intratumoral concentrations of paclitaxel are too low to cause mitotic arrest and result in multipolar divisions instead. It is hoped that this insight can now be used to develop a biomarker to identify the ∼50% of patients that will benefit from paclitaxel therapy. Here I discuss the history of paclitaxel and our recently evolved understanding of its mechanism of action.

Withaferin a synergistically enhances the effects of paclitaxel against lung cancer.

“…In support of Weaver et al, [64], the median inhibitory concentrations of PAC were between 8-25 nM, concentrations which were previously reported to be clinically relevant.…”

“…PAC is a potent inducer of apoptosis in many normal and cancer cell types, but, as noted earlier, the induction of apoptosis by PAC is both time and concentration dependent [64]. This is because sufficient time is required to allow effective concentrations of PAC to build up in cancer cells.…”

“…PAC or taxol, a member of the taxanes was first approved by FDA for the treatment of NSCLC in 1999 [64].…”

“…Mechanistically, PAC acts by binding to β-tubulin and stabilizing microtubules during cell division causing mitotic arrest [64]. Whether cells undergo apoptosis or not following mitotic arrest by PAC is dependent on efficient mitotic checkpoint mechanisms which are often dysregulated in NSCLC cells.…”

Substancje pochodzenia roślinnego w terapii nowotworów

“…Wydaje się, że to właśnie ten mechanizm związany z hamowaniem dynamiki mikrotubul wrzeciona podziałowego ma największe znaczenie w przypadku działania takich leków, jak paklitaksel, winblastyna i winkrystyna (11). Istnieją również dane, że klinicznie istotne stężenia paklitakselu mogą powodować śmierć komórki nie w wyniku zahamowania mitozy, ale poprzez podziały wielobiegunowe i nieprawidłową segregację chromosomów (15).…”