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Effects of different autophagy inhibitors on sensitizing KG ‐1 and HL ‐60 leukemia cells to chemotherapy
Author(s) -
Haghi Atousa,
Salemi Mahdieh,
Fakhimahmadi Aila,
Mohammadi Kian Mahnaz,
Yousefi Hassan,
Rahmati Marveh,
Mohammadi Saeed,
Ghavamzadeh Ardeshir,
Moosavi Mohammad Amin,
Nikbakht Mohsen
Publication year - 2021
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2411
Subject(s) - autophagy , arsenic trioxide , acridine orange , myeloid leukemia , apoptosis , chemistry , mtt assay , acute promyelocytic leukemia , cytotoxicity , cytotoxic t cell , cancer research , leukemia , lamp1 , retinoic acid , microbiology and biotechnology , biology , immunology , in vitro , biochemistry , gene
A little number of current autophagy inhibitors may have beneficial effects on the acute myeloid leukemia (AML) patients. However, there is a strong need to figure out which settings should be activated or inhibited in autophagy pathway to prevail drug resistance and also to improve current treatment options in leukemia. Therefore, this study aimed to compare the effects of well‐known inhibitors of autophagy (as 3‐MA, BafA1, and HCQ) in leukemia KG‐1 and HL‐60 cells exposed to arsenic trioxide (ATO) and/or all‐trans retinoic acid (ATRA). Cell proliferation and cytotoxicity of cells were examined by MTT assay. Autophagy was studied by evaluating the development of acidic vesicular organelles, and the autophagosomes formation was investigated by acridine orange staining and transmission electron microscopy. Moreover, the gene and protein expressions levels of autophagy markers ( ATGs , p62/SQSTM1, and LC‐3B) were also performed by qPCR and western blotting, respectively. The rate of apoptosis and cell cycle were evaluated using flow cytometry. We compared the cytotoxic and apoptotic effects of ATO and/or ATRA in both cell lines and demonstrated that some autophagy markers upregulated in this context. Also, it was shown that autophagy blockers HCQ and/or BafA1 could potentiate the cytotoxic effects of ATO/ATRA, which were more pronounced in KG‐1 cells compared to HL‐60 cell line. This study showed the involvement of autophagy during the treatment of KG‐1 and HL‐60 cells by ATO/ATRA. This study proposed that therapy of ATO/ATRA in combination with HCQ can be considered as a more effective strategy for targeting leukemic KG‐1 cells.