An Overview of the Taxol Anti-Cancer drug, Its Biosynthetic Pathway, Extraction, and its Mechanism on Cancer Cells

An Overview of the Taxol Anti-Cancer drug, Its Biosynthetic Pathway, Extraction, and its Mechanism on Cancer Cells
Yalda Zhoolideh,^1,*
1. Islamic Azad University Of Tabriz
Introduction: Medicinal herbs make up more than 25% of the world's total medicines, which play a special role in providing anticancer drugs. That Taxol and its constituents (Taxanes) or (Taxoid) are of great importance. Taxol is a de-terpenoids alkaloid approved for use in the treatment breast, ovarian and lung cancers as well as AIDS-associated Kaposi's sarcoma. Recent research has shown that hazelnut and its cellular properties also produce detaxan components, including Taxol. In addition, the efficacy of these drugs in other diseases, including polycystic liver disease and Alzheimer's, has been proven in many studies and clinical trials. Taxanes are secondary metabolites and diterpene compounds that protect the plant against wounds and plant pathogens. The accumulation of secondary metabolites in plants is part of the immune response to pathogenic attacks induced and activated by stimuli. Stimulants commonly used in studies include fungal carbohydrates, yeast extract, methyl jasmonate (MJ), salicylic acid, and Chitosan. The natural source of taxons is a species of yew tree. Yew (Taxus baccata) is a coniferous tree that is a living legend and the masterpiece of northern Iran's forests since the third geology.
Methods: Articles related to the subject were searched on two sites of Science Direct and Google scholar, and 24 articles that examined the Taxol Anticancer drug, Its Biosynthetic Pathway, Extraction, and its Mechanism on Cancer Cells were included in the study.
Results: Despite many efforts to identify the biosynthetic pathway of Taxol, a clear and precise conception of it is still not available. High diversity of taxon compounds and their similarity to each other, low concentrations of intermediate compounds and many metabolic stages are the most important barriers to the recognition of this biosynthetic pathway. However, researchers using a combination of biochemical and genetic techniques and have succeeded in providing a relatively clear idea of this biosynthetic pathway. Due to its scarcity, slow growth and very low concentration in the natural plant, as well as the presence of more than 400 similar compounds that make the purification process very complicated, extraction of these materials from the plant is not a cost-effective method and has been replaced by other methods. Chemical synthesis, semi-synthesis, and microbial production are some of the methods commonly used to replace previous methods, but very low yields due to the production of many undesirable isomers, large fluctuations in precursor production and very low production compared to the plant itself. The most important problems with these methods are. Nowadays, plant cell culture is recognized as one of the alternatives and reproducible sources for the production of secondary metabolites. The exact mechanism of Taxol for cytotoxicity against tumor cells is not completely clear. Taxol inhibits microtubule depolymerization and promotes the formation of highly stable microtubules, thereby disrupting the normal dynamic reorganization of the microtubule network required for mitosis and cell proliferation. Taxol drives inactive GDP-tubulin into microtubules, replacing the need of the g-phosphate of GTP to activate the protein. Taxol stabilizes microtubules by binding preferentially to assemble tubulin with an exact 1:1 stoichiometric ratio. Unpolymerized tubulin has no significant affinity for Taxol, indicating that the binding site is formed during the polymerization process. Another Taxol's therapeutic feature is high effect in inducing cell cycle arrest in human glioblastoma cells. One more mechanism of Taxol is Induction of Apoptosis. Apoptosis, the terminal point of programmed cell death, is well characterized by morphological and biochemical features. Several lines of evidence from recent studies have suggested that Taxol induces apoptosis through a signaling mechanism independent of microtubule and mitotic arrest. Taxol is highly effective in inducing cell cycle arrest in human glioblastoma cells.
Conclusion: As mentioned, there is some difficulty in extracting this material, however, understanding the expression and expression level of different genes and identifying the key genes involved in Taxol biosynthesis can guide us in directing Taxol biosynthetic pathway genes in yew. Also, because the Taxol biosynthesis pathway has not been fully identified, studying gene expression patterns and proteomics analysis could be helpful in helping to better treat cancer.
Keywords: Taxol, Cancer, Anticancer drug