Combination treatment of Src inhibitor Saracatinib with GMI, a Ganoderma microsporum immunomodulatory protein, induce synthetic lethality via autophagy and apoptosis in lung cancer cells

Saracatinib is an oral Src‐kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein from Ganoderma microsporum, possesses antitumor capacity. The aim of this study is to evaluate the cytotoxic effect of combination trea...

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Published in:Journal of cellular physiology 2021-02, Vol.236 (2), p.1148-1157
Main Authors: Chiu, Ling‐Yen, Hsin, I‐Lun, Tsai, Jen‐Ning, Chen, Chih‐Jung, Ou, Chu‐Chyn, Wu, Wen‐Jun, Sheu, Gwo‐Tarng, Ko, Jiunn‐Liang
Format: Article
Language:English
Subjects:
Annexin V
Apoptosis
Autophagy
Caspase
Cell activation
Cell death
Clinical trials
Combined treatment
Cytotoxicity
Drug resistance
Enzyme inhibitors
Ganoderma
GMI
Immunomodulation
Iodides
Kinases
Lethality
Lung cancer
Phagocytosis
Propidium iodide
Proteins
saracatinib
Src
Src protein
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Summary:Saracatinib is an oral Src‐kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein from Ganoderma microsporum, possesses antitumor capacity. The aim of this study is to evaluate the cytotoxic effect of combination treatment with saracatinib and GMI on parental and pemetrexed‐resistant lung cancer cells. Cotreatment with saracatinib and GMI induced synergistic and additive cytotoxic effect in A549 and A400 cells by annexin V/propidium iodide assay and combination index. Using western blot assay, saracatinib, and GMI combined treatment synergistically induced caspase‐7 activation in A549 cells. Different from A549 cells, saracatinib and GMI cotreatment markedly increased LC3B‐II in A400 cells. ATG5 silencing abolished the caspase‐7 activation and reduced cell death in A549 cells after cotreatment. This is the first study to provide a novel strategy of treating lung cancer with or without drug resistance via combination treatment with GMI and saracatinib. Saracatinib is an oral Src‐kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein from Ganoderma microsporum, possesses antitumor capacity. Cotreatment with saracatinib and GMI induced synergistic and additive cytotoxic effect in A549 and A400 cells via autophagy and apoptosis.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.29924