XQ2, a novel TPZ derivative, induced G2/M phase arrest and apoptosis under hypoxia in non-small cell lung cancer cells.

Abstract

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.

• Authors: Jianshu Lou, XingLu Zhou, Qinjie Weng, Duo-duo Wang, Qing Xia, Yongzhou Hu, Qiaojun He, Bo Yang, Peihua Luo
• Journal: Bioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 74 Issue 6 Pg. 1181-7 ( 2010) ISSN: 1347-6947 [Electronic] England
• PMID: 20530905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cyclic N-Oxides
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• N-ethoxymethyl-3-amino-1,2,4-benzotriazine-1,4-dioxide
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Triazines
• bcl-2-Associated X Protein
• Tirapazamine
• Poly(ADP-ribose) Polymerases
• Caspase 3
• Caspase 9

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (pathology)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Cell Division (drug effects)
• Cell Hypoxia
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclic N-Oxides (chemistry, pharmacology)
• G2 Phase (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Mitochondria (drug effects, metabolism)
• Poly(ADP-ribose) Polymerases (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Tirapazamine
• Triazines (chemistry, pharmacology)
• bcl-2-Associated X Protein (metabolism)