Open AccessChloroquine and hydroxychloroquine inhibit bladder cancer cell growth by targeting basal autophagy and enhancing apoptosis
Author(s) -
Lin YiChia,
Lin JiFan,
Wen ShengI,
Yang ShanChe,
Tsai TeFu,
Chen HungEn,
Chou KuangYu,
Hwang Thomas ISheng
Publication year - 2017
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1016/j.kjms.2017.01.004
Subject(s) - autophagy , apoptosis , medicine , bladder cancer , hydroxychloroquine , clonogenic assay , chloroquine , cancer research , cancer cell , cell culture , caspase 3 , pharmacology , cisplatin , cell growth , cancer , programmed cell death , immunology , chemotherapy , biology , biochemistry , genetics , disease , covid-19 , malaria , infectious disease (medical specialty)
Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro . The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time‐ and dose‐dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV‐Huc‐1) or other reference cancer cell lines (PC3 and MCF‐7). We found that 24‐hour treatment of CQ or HCQ significantly decreased the clonogenic formation in 5637 and T24 cells compared to SV‐Huc‐1. As human bladder cancer tumor exhibits high basal level of autophagic activities, we detected the autophagic flux in cells treated with CQ and HCQ, showing an alternation in LC3 flux in CQ‐ or HCQ‐treated cells. Moreover, bladder cancer cells treated with CQ and HCQ underwent apoptosis, resulting in increased caspase 3/7 activities, increased level of cleaved poly(ADP‐ribose) polymerase (PARP), caspase 3, and DNA fragmentation. Given these results, targeting autophagy with CQ and HCQ represents an effective cancer therapeutic strategy against human bladder cancer.