Polyamine transporter recognization and antitumor effects of anthracenymethyl homospermidine.
This study was conducted to examine the polyamine transporter (PAT) recognization and antitumor effects of anthracenymethyl homospermidine (ANTMHspd) and its apoptotic mechanism in B16 melanoma cells. ANTMHspd promoted a dose-dependent apoptosis in B16 melanoma cells and the apoptosis was associated with the excellent PAT recognization, externalization of cell membrane phosphatidylserine and the disruption of mitochondria, these processes were correlated with up-regulation of polyamine oxidase, an increase in intracellular reactive oxygen species (ROS) production and oxidative stress. In addition, reduction of MMP, release of cytochrome c, up-regulation of Bax protein expression, down-regulation of Bcl-2 protein expression, and activation of caspase-3, caspase-9 were also observed in B16 cells after treatment with ANTMHspd. Furthermore, N-acetylcysteine obviously antagonized ANTMHspd-induced apoptosis. Importantly, ANTMHspd was found to be better tolerated and revealed potent antitumor effect on inhibiting tumor growth in situ and suppressing pulmonary metastasis in xenograft mice model. These data demonstrate that ANTMHspd is an excellent PAT recognization and potent antitumor agent.
Xie
Song-Qiang
SQ
The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475001, China.
Wang
Jian-Hong
JH
Ma
Hong-Xia
HX
Cheng
Peng-Fei
PF
Zhao
Jin
J
Wang
Chao-Jie
CJ
D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008175:Lung Neoplasms / Q000517:prevention & control; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D009362:Neoplasm Metastasis / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D011073:Polyamines / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013095:Spermidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000873:Anthracenes; D000970:Antineoplastic Agents; D003574:Cytochrome c Group; D026901:Membrane Transport Proteins; D011073:Polyamines; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C529696:anthracenylmethyl homospermidine; D051028:bcl-2-Associated X Protein; C076615:cytochrome c''; D053148:Caspase 3; D053453:Caspase 9; D020782:Matrix Metalloproteinases; D013095:Spermidine; D000111:Acetylcysteine