title: Mononaphthalimide spermidine conjugate induces cell proliferation inhibition and apoptosis in HeLa cells.
abstract: Developing polyamine-drug conjugates that are capable of specific entry to tumor cells is attractive in improving chemotherapeutic efficacy. Currently, the exact cytotoxic mechanism of these conjugates is not well known. Here, our research revealed the effect of a mononaphthalimide-spermidine (MNISpd) conjugate on the growth and survival of HeLa cells and possible mechanisms. In characterizing the mechanism of MNISpd cytotoxicity, inhibition of proliferation is observed in the 0.5-6 μM range and there is evidence of apoptosis at equal or greater than 6 μM, but with less toxicity on HELF cell. The lower concentrations of MNISpd induced a cell cycle arrest correlated with enhanced p21 expression and decreased cdc2 but not Cdk2 expression. MNISpd-induced apoptosis was correlated with caspase-3 activation, decreased XIAP expression and a loss of mitochondrial membrane potential. Apoptosis but not cell cycle arrest was susceptible to N-acetyl-L-cysteine (NAC) treatment. It is proposed that MNISpd-induced apoptosis in HeLa cells is related to oxidative stress and that at lower exposure concentrations effects on cell proliferation predominate while at higher concentrations apoptosis develops.
authors.affiliation: Key Laboratory of Special Function Material, Henan University, Kaifeng 475004, China.
authors.forename: Lianhe
authors.initials: L
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Tian
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.forename: Chaojie
authors.initials: C
authors.lastname: Wang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008168:Lung / Q000166:cytology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053644:Naphthalimides / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D013095:Spermidine / Q000737:chemistry / Q000494:pharmacology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D053644:Naphthalimides; D051636:X-Linked Inhibitor of Apoptosis Protein; D053148:Caspase 3; D013095:Spermidine; D000111:Acetylcysteine