Taxo Taxol Case Study

Taxol is an anticancer drug produced by extraction from the bark of the pacific yew tree called Taxus brevifolia, which was discovered by Harvard trained botanist called Arthur Barclay in 1962 (wall and wani, 1995). It was renamed to paclitaxel when it was commercially developed. It is in a form of whitish crystalline powder with a melting point of 216 ºC, very insoluble in water, highly lipophilic, higher protein binding rate and disturbs the structure of the inner part of the cell membrane (Goldspiel, 1997) and (Ledwitch et al., 2013). It contains heptadecane (17-carbon) skeleton with a structural formula of C47 H51 NO14 and a molecular weight of 853.9 g/mol. The antitumor activity of the drug is mainly due to the side chain; a ring, oxetane ring and C2 benzoyl group (Priyadarshini and Keerthi, 2012).
It is widely used in the treatment of ovarian, cervical, lung, and breast cancer. It prevents cell proliferation by binding to the N-terminal 31 amino acids of the beta-tubulin subunit in the microtubule, inhibit microtubule depolymerization and promotes polymerization of tubulin into stable microtubules (Ganguly et al.,2010) and (Ganesh et al.,2007). This stability result in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for proper alignment and chromatid separation (Bharadwaj and Yu, 2004). Taxol form stable and dysfunctional microtubules which can no longer maintain shape, motility, signal transmission, and intracellular transport in interphase and stable microtubules fails to bind to centromere to align chromosomes in metaphase and separate non sister chromatids in anaphase. This induces cell cycle arrest; inhibit cellular replication and causes cell death (Rowinsky et al.,