Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis

Liu,Likun; Han,Cuicui; Yu,Haitao; Zhu,Wenbin; Cui,Hongxia; Zheng,Lihong; Zhang,Chunjing; Yue,Liling

doi:10.3892/or.2018.6363

Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis

Authors:
- Likun Liu
- Cuicui Han
- Haitao Yu
- Wenbin Zhu
- Hongxia Cui
- Lihong Zheng
- Chunjing Zhang
- Liling Yue
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Affiliations: Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Biology Genetics, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Clinical Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Biochemistry, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China
Published online on: April 12, 2018 https://doi.org/10.3892/or.2018.6363
Pages: 2807-2816

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Abstract

Chloroquine (CQ) has been revealed to exhibit antitumor activity in several human tumors including lung cancer as mono‑ or add‑on therapy. The antitumor effect of CQ appears to depend on the tumor type, stage and genetic context. Few studies have focused on the mechanism concerning the antitumor effect of CQ monotherapy and the cause and effect relationship among autophagy, apoptosis and CQ in human lung A549 cells. Therefore, the present study aimed to identify the antitumor effect of CQ monotherapy and analyze the possible mechanism. In the present study, we demonstrated that CQ suppressed human A549 cell growth in a dose‑ and time‑dependent manner. CQ‑mediated growth inhibition in A549 cells was characterized by the targeting of the PI3K/AKT pathway, thus, inducing mitochondria‑mediated apoptosis at relatively higher concentrations by downregulating Bcl‑2 expression, increasing the expression level of Bax, decreasing mitochondrial membrane potential, releasing cytochrome c from the mitochondria into the cytosol, activating caspase‑3 and cleaving PARP. Collectively, these findings may offer a new rationale for using CQ as a lung cancer therapy drug in clinical practice.

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