XQ2, a novel TPZ derivative, induced G2/M phase arrest and apoptosis under hypoxia in non-small cell lung cancer cells.
Hypoxia is one of the inevitable circumstances of various tumors. It controls various levels of regulation in tumor progression and results in tumor resistance to radiotherapy and chemotherapy. Here we investigated a synthetic TPZ derivative, N-ethoxymethyl-3-amino-1,2,4-benzotriazine-1,4-dioxide (XQ2), a novel compound that induced anti-cancer effects both in normoxia and in hypoxia, cell proliferation assay found that XQ2 exhibited a potent inhibitory effect on the tested cancer cell lines both in normoxia and in hypoxia. Flow cytometry and western blot studies indicated that XQ2 induces G2/M arrest and a caspase-dependent apoptosis in A549 cells. Additionally, intracellular reactive oxygen species (ROS) appear to play a key role in the anticancer effect of XQ2 in hypoxia. Taken together, our data suggest that XQ2 exerted anticancer action by suppressing the ROS level and triggering cell-cycle arrest and the caspase-dependent pathway, which is associated with apoptosis.
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Jianshu
J
Lou
XingLu
X
Zhou
Qinjie
Q
Weng
Duo-duo
DD
Wang
Qing
Q
Xia
Yongzhou
Y
Hu
Qiaojun
Q
He
Bo
B
Yang
Peihua
P
Luo
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000737:chemistry* / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077704:Tirapazamine; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C552435:N-ethoxymethyl-3-amino-1,2,4-benzotriazine-1,4-dioxide; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014227:Triazines; D051028:bcl-2-Associated X Protein; D000077704:Tirapazamine; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9