Comparative study of microtubule inhibitors - Estramustine and natural podophyllotoxin conjugated PAMAM dendrimer on glioma cell proliferation
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- 作者：Ugir Hossain Sk ; Deobrat Dixit ; Ellora Sen
- 关键词：Dendrimer-drug conjugation ; Estramustine ; Podophyllotoxin ; Cell cycle ; Tubulin depolymerization
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：68
- 期：Complete
- 页码：47-57
- 全文大小：2807 K
文摘
The synthetic estramustine (EM) and natural podophyllotoxin (PODO) anti-mitotic agents that inhibit tubulin polymerization are known anticancer agents. As low bioavailability limits their anticancer properties, we investigated whether conjugation with PAMAM dendrimer (D) could enhance the activity of D-EM and D-PODO by altering their release pattern. Release kinetics indicated synthesized conjugates to be stable against hydrolytic cleavage and showed sustained release characteristics. However, release of D-EM was slow compared to D-PODO conjugate. Antitumor effect of these conjugates on glioma cells revealed (i) increased cell death and cell cycle arrest (ii) decreased migration and (iii) increased tubulin depolymerization as compared to free drug. Importantly, the effects of natural PODO conjugate on glioma cell survival and migration is more pronounced than D-EM.