NPC-16, a novel naphthalimide-polyamine conjugate, induced apoptosis and autophagy in human hepatoma HepG2 cells and Bel-7402 cells.
The antitumor effects and molecular mechanism of NPC-16, a novel naphthalimide-polyamine conjugate, were evaluated in HepG2 cells and Bel-7402 cells. Apoptosis and necrosis were evaluated by Annexin V-FITC detection kit, and autophagy by acridine orange and Lyso-Tracker Red staining. The change of mitochondrial transmembrane potential was measured using rhodamine 123 staining. The protein expression of Beclin 1, LC3 II and mTOR, p70S6 K, 14-3-3, caspase, and Bcl-2 family members was detected by immunofluorescence assays and Western Blot. Here, we elucidated the nature of cellular response of HepG2 cells and Bel-7402 cells to NPC-16 at IC(50). NPC-16 induced caspase-dependent apoptosis via the mitochondrial pathway and death receptor pathway in Bel-7402 cells. Differently, NPC-16 triggered HepG2 cells both apoptosis and autophagy, further autophagy facilitated cellular apoptosis. Furthermore, mTOR signal pathway was involved in NPC-16-mediated autophagy in HepG2 cells. Thus, NPC-16 may be useful as a potential template for investigation the molecular mechanism of naphthalimide-polyamine conjugate against hepatocellular carcinoma.
Xie
Song-qiang
SQ
Institute of Chemical Biology, Henan University, Kaifeng, China.
Li
Qian
Q
Zhang
Ya-hong
YH
Wang
Jian-hong
JH
Mei
Zi-hou
ZH
Zhao
Jin
J
Wang
Chao-jie
CJ
D000165:Acridine Orange / Q000032:analysis; D017304:Annexin A5 / Q000032:analysis; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053644:Naphthalimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009336:Necrosis; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D017304:Annexin A5; D000964:Antimetabolites, Antineoplastic; D047908:Intracellular Signaling Peptides and Proteins; C559142:NPC 16; D053644:Naphthalimides; D011073:Polyamines; D053218:Receptors, Death Domain; D000165:Acridine Orange