Human non-small cell lung cancer cells can be sensitized to camptothecin by modulating autophagy
Journal
International Journal of Oncology
Journal Volume
53
Journal Issue
5
Pages
1967-1979
Date Issued
2018
Author(s)
Chiu Y.-H.
Hsu S.-H.
Hsu H.-W.
Huang K.-C.
Liu W.
Wu C.-Y.
Huang W.-P.
Chen J.Y.-F.
Chen B.-H.
Abstract
Lung cancer is a prevalent disease and is one of the leading causes of mortality worldwide. Despite the development of various anticancer drugs, the prognosis of lung cancer is relatively poor. Metastasis of lung cancer, as well as chemoresistance, is associated with a high mortality rate for patients with lung cancer. Camptothecin (CPT) is a well-known anticancer drug, which causes cancer cell apoptosis via the induction of DNA damage; however, the cytotoxicity of CPT easily reaches a plateau at a relatively high dose in lung cancer cells, thus limiting its efficacy. The present study demonstrated that CPT may induce autophagy in two human non-small cell lung cancer cell lines, H1299 and H460. In addition, the results of a viability assay and Annexin V staining revealed that CPT-induced autophagy could protect lung cancer cells from programmed cell death. Conversely, the cytotoxicity of CPT was increased when autophagy was blocked by 3-methyladenine treatment. Furthermore, inhibition of autophagy enhanced the levels of CPT-induced DNA damage in the lung cancer cell lines. Accordingly, these findings suggested that autophagy exerts a protective role in CPT-Treated lung cancer cells, and the combination of CPT with a specific inhibitor of autophagy may be considered a promising strategy for the future treatment of lung cancer. ? 2018 Spandidos Publications. All rights reserved.
SDGs
Other Subjects
3 methyladenine; camptothecin; lipocortin 5; 3-methyladenine; adenine; antineoplastic agent; benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; camptothecin; caspase inhibitor; H2AFX protein, human; histone; peptide chloromethyl ketone; apoptosis; Article; autophagosome; autophagy; cell migration assay; cell viability assay; cytochemistry; DNA damage; drug cytotoxicity; drug effect; drug sensitization; flow cytometry; human; human cell; NCI-H1299 cell line; NCI-H460 cell line; non small cell lung cancer; priority journal; Western blotting; analogs and derivatives; autophagy; cell motion; dose response; drug resistance; IC50; lung tumor; metabolism; non small cell lung cancer; pathology; tumor cell line; Adenine; Amino Acid Chloromethyl Ketones; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Autophagy; Camptothecin; Carcinoma, Non-Small-Cell Lung; Caspase Inhibitors; Cell Line, Tumor; Cell Movement; DNA Damage; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Histones; Humans; Inhibitory Concentration 50; Lung Neoplasms
Type
journal article