Exploration of mitotic poisons from plants a detailed investigation on the anticancer and antimitotic activities of securinine and zerumbone

Abstract

Microtubules are a key component of the cytoskeleton that plays a crucial role in cell newlinedivision and many other vital cellular processes. They are highly dynamic in nature and newlineundergo polymerization and depolymerization in a short span of time. newlineAll the cellular functions of microtubules are highly dependent on their polymerization newlinedynamics. Molecules that target polymerization dynamics of microtubules are also newlineknown as mitotic poisons. And they inhibit the metaphase-anaphase transition in the newlinedividing cells. Prolonged mitotic arrest leads to apoptosis through various signaling newlinepathways. Several small molecules that target microtubules have been developed with newlinedifferent aims such as anticancer drugs, pesticides, anthelmintic and antifungal drugs newlinesince it is vital for cell division and other important cellular processes. Antimitotic newlinedrugs that disrupt the normal functioning of mitotic spindle have proven to be the most newlineeffective chemotherapeutic drugs and most of them are derived from natural sources. newlineChemotherapeutic drugs like vincristine, vinblastine, paclitaxel, podophyllotoxin, newlinecamptothecin, and combretastatin are good examples of clinically successful antimitotic newlineagents. Securinine and zerumbone are two plant-derived molecules that are proven to newlinepossess strong anticancer activity against different cancer cell lines. However, the newlinemechanism behind their cytotoxicity is not investigated in detail. newlineSecurinine is a plant-derived alkaloid present in the roots of the Securinega suffruticosa. newlineSecurinine effectively prevented the proliferation of cervical, breast, and lung cancer newlinecells with an IC50 of 6, 10, and 11 and#956;M respectively and induced minimal toxicity in newlinenormal HEK cell lines. Securinine at concentrations higher than IC50 induced newlinesignificant depolymerization in interphase and mitotic microtubules. It effectively newlinesuppressed the migration of HeLa cells indicating its potential as an anticancer drug.