Human non‑small cell lung cancer cells can be sensitized to camptothecin by modulating autophagy

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.

Defining COMMD4 as an anti-cancer therapeutic target and prognostic factor in non-small cell lung cancer

“…As NSCLC cells depleted of COMMD4 were hypersensitive to irradiation, we next investigated whether COMMD4 depletion might also enhance sensitivity to camptothecin in NSCLC cells. Camptothecin class of compounds have shown promise in the treatment of many cancers including NSCLC 38 and function by generating cytotoxic single-strand DNA breaks that are processed into DNA double-strand breaks during the S-phase of the cell cycle. 39 While we observed no difference in the sensitivity between control and COMMD4 siRNA-depleted HBEC3-KT cells (Fig.…”

Involvement of Actin in Autophagy and Autophagy-Dependent Multidrug Resistance in Cancer

“…This indicates the participation of autophagy in the development of MDR. Prosurvival role of autophagy was also confirmed in breast, ovarian, esophageal, lung, prostate, renal and pancreatic cancers [98,99,100,101,102,103,104]. Similar effect was observed in the case of glioma and bladder cancer [106,107].…”

“…As MDR is responsible for most of the chemotherapy failures, its inhibition would be of great importance for oncological patients [97]. Recent literature reports indicate the process of autophagy may, in at least some cases, be the basis of MDR, but the relationship between these phenomena is still not fully understood [98,99,100,101,102,103,104]. Like in the initiation and progression of cancer also in the case of MDR, the role of autophagy may be twofold.…”

Dovitinib Triggers Apoptosis and Autophagic Cell Death by Targeting SHP-1/p-STAT3 Signaling in Human Breast Cancers

“…Recent studies reported that dovitinib showed antitumor activity by inhibiting cell proliferation and inducing apoptosis in breast and colorectal cancer cells [31, 32]. However, accumulated studies suggest that autophagy induces chemoresistance against chemotherapeutic agents by inhibiting apoptosis of cancer cells [33]. Our prior finding showed that dovitinib increased autophagy in various breast cancer cells, and the antitumor effect of dovitinib could be restricted by autophagic cell death.…”