title: Comparative study of microtubule inhibitors--estramustine and natural podophyllotoxin conjugated PAMAM dendrimer on glioma cell proliferation.
abstract: 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.
authors: Natural Plant Products Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, (H.P.) 176 061, India. Electronic address: ugir@ihbt.res.in.
authors: Ugir Hossain
authors: UH
authors: Sk
authors: Deobrat
authors: D
authors: Dixit
authors: Ellora
authors: E
authors: Sen
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D004961:Estramustine / Q000737:chemistry / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000737:chemistry / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D050257:Tubulin Modulators; D004961:Estramustine; D011034:Podophyllotoxin
keywords: Cell cycle; Dendrimer-drug conjugation; Estramustine; Podophyllotoxin; Tubulin depolymerization