A triazole-conjugated benzoxazone induces reactive oxygen species and promotes autophagic apoptosis in human lung cancer cells

Autor: Chien-Chih Chiu, Chun Yen Liu, Kang Fang, Ching Fa Yao, Chang Heng Hsieh, Jing Ping Wang
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
Lung Neoplasms
Poly ADP ribose polymerase
Injections
Subcutaneous
Clinical Biochemistry
Cell
Pharmaceutical Science
Mice
Nude
Antineoplastic Agents
Apoptosis
Heterocyclic Compounds
2-Ring
03 medical and health sciences
Mice
0302 clinical medicine
Carcinoma
Non-Small-Cell Lung
medicine
Autophagy
Animals
Humans
Lung cancer
Cytotoxicity
Pharmacology
chemistry.chemical_classification
A549 cell
Reactive oxygen species
Mice
Inbred BALB C
Caspase 3
Biochemistry (medical)
Cell Cycle
Cell Biology
Triazoles
medicine.disease
Xenograft Model Antitumor Assays
Benzoxazines
Gene Expression Regulation
Neoplastic
030104 developmental biology
medicine.anatomical_structure
chemistry
A549 Cells
030220 oncology & carcinogenesis
Cancer research
Poly(ADP-ribose) Polymerases
Tumor Suppressor Protein p53
Reactive Oxygen Species
Microtubule-Associated Proteins
Signal Transduction
Zdroj: Apoptosis : an international journal on programmed cell death. 23(1)
ISSN: 1573-675X
Popis: Numerous approaches suggested that compounds with conjugated triazole moieties or benzoxazone pharmacores are effective to antagonize proliferation of human tumors. The current study reported that a synthetic triazole-conjugated benzoxazone, 4-((5-benzyl-1H-1,2,3-triazol-3-yl)-methyl)-7-methoxy-2H-benzo[b][1,4]-oxazin-3(4H)-one (BTO), inhibited growth rates of human non-small cell lung cancer cells. The cytotoxicity can be enhanced with increasing drug concentrations. More evidence supported that the induced reactive oxygen species lead to ultimate apoptotic cell death by recruiting autophagy. The mechanistic pathway as elucidated involved tumor suppressor p53 activation and LC3-1 conversion followed by PARP and procaspase-3 cleavage. Autophagy inhibition reverted apoptotic death and restored cell viabilities. BTO suppressed the development of A549 cell xenograft tumors by activating autophagy and apoptosis simultaneously. As an efficient tumor growth inhibitor with relatively small molecular weight, BTO is a viable addition to the existing list of lung cancer treatment.
Databáze: OpenAIRE
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