Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling.
Cancer stem cells (CSCs) have recently been linked to new treatment strategies for gastric cancer due to the critical role which they play as the 'heartbeat' of cancer. In the present study, we explored the effects of quercetin, an anti-inﬂammatory and antiviral compound, on gastric CSCs (GCSCs). We noted that quercetin exerted pronounced inhibitory effects on GCSC survival. Moreover, quercetin induced cell apoptosis in a mitochondrial-dependent manner, as shown by the reduction in mitochondrial membrane potential, the activation of caspase-3 and -9, and the downregulation of Bcl-2, as well as the upregulation of Bax and cytochrome c (Cyt-c). Additionally, a marked decrease in Akt phosphorylation levels was observed following treatment with quercetin, whereas pre-treatment with fumonisin B1 (FB1, Akt activator) significantly attenuated the inhibitory effects of quercetin on cell growth and its promoting effects on mitochondrial-dependent apoptosis. Notably, FB1 enhanced the expression of Bcl-2, which was inhibited by quercetin, and prevented the decrease in mitochondrial membrane potential induced by quercetin. However, the increase in the levels of caspases, Bax and Cyt-c induced by quercetin was also attenuated by the addition of FB1 to the GCSCs. Therefore, our results demonstrate that quercetin triggers mitochondrial apoptotic-dependent growth inhibition via the blockade of phosphoinositide 3-kinase (PI3K)-Akt signaling in GCSCs, indicating a potential target for the treatment of gastric cancer.
Department of Minimally Invasive Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Xinsheng
X
Shen
Department of Minimally Invasive Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Yaqing
Y
Si
Department of Minimally Invasive Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Zhao
Z
Wang
Department of Minimally Invasive Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Jiachen
J
Wang
Department of Minimally Invasive Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Yongqiang
Y
Guo
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Xiefu
X
Zhang
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology*
D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt