Journal
ANTICANCER RESEARCH
Volume 40, Issue 3, Pages 1405-1417Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.14082
Keywords
Niclosamide; caspase-independent pathway; autophagy; AMPK/AKT/mTOR pathway; NSCLC
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Funding
- Changhua Christian Hospital, Taiwan [107-CCH-HCR-027]
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Background/Aim: Niclosamide is an antihe-minthic drug that has shown cytotoxic effects on non-small cell lung carcinoma (NSCLC) cells. However, the exact mechanisms underlying the anti-tumour activity of niclosamide in NSCLC cancer cells remains to be defined. The aim of this study was to evaluate the antitumor activity of niclosamide in human A549 and CL1-5 non-small cell lung cancer cells using in vitro and in vivo. Materials and Methods: We investigated the effects of niclosamide on cell viability, apoptosis, the mitochondrial membrane potential (MMP; Delta phi m), and autophagy and apoptosis-related protein expression in human A549 and CL1-5 non-small cell lung cancer cells. Results: Niclosamide induced mainly caspase-independent apoptosis through apoptosis-inducible factor (AIF) translocation to the nucleus upon mitochondria damage. Moreover, niclosamide-induced autophagy may act as adaptive response against apoptosis. AMPK/AKT/mTOR pathway were involved in niclosamide-induced cell death and autophagy in response to ATP depletion. Furthermore, niclosamide efficiently suppressed tumor growth and induce autophagy in vivo. Conclusion: Niclosamide induced apoptosis by activating the intrinsic and caspase-independent pathway in human A549 and CL1-5 non-small cell lung cancer cells. Therefore, niclosamide is a potential candidate for anti-NSCLC therapy.
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