TY - JOUR
T1 - Gen-27, a newly synthesized flavonoid, inhibits glycolysis and induces cell apoptosis via suppression of hexokinase II in human breast cancer cells
AU - Tao, Lei
AU - Liu, Yishi
AU - Ding, Yang
AU - Liu, Xiuting
AU - Zhang, Xin
AU - Hu, Rong
AU - Wei, Libing
AU - Wang, Xiaoping
AU - Yao, Yuyuan
AU - Lu, Jinrong
AU - Wang, Qing
N1 - Publisher Copyright:
© 2016
PY - 2017/2/1
Y1 - 2017/2/1
N2 - We have previously reported that Gen-27, a newly synthesized flavonoid, exhibits anticancer effects against human colorectal cancer cells. In this study, we investigated the anticancer effects in human breast cancer cell lines and its underlying mechanisms. We demonstrated that Gen-27 inhibited the growth and proliferation of human breast cancer cells in concentration and time-dependent manners. It was found that Gen-27 induced mitochondrial-mediated apoptosis, characterized by the dissipation of mitochondrial membrane potential (ΔΨm), cytochrome c (Cyt c) release from mitochondria to cytosol, activation of caspases and induction of poly (ADP-ribose) polymerase (PARP). In addition, Gen-27 inhibited the glycolysis in human breast cancer cells. After treatment with Gen-27, the expression of HKII was down-regulated, accompanied by weakened interaction of HKII and VDAC. Further research revealed that the induction of mitochondrial apoptosis was associated with the decrease of HKII expression by Gen-27. Finally, in vivo studies demonstrated that Gen-27 significantly suppressed the growth and promoted apoptosis of MDA-MB-231 breast cancer orthotopic tumors with low systemic toxicity. In conclusion, the results showed that Gen-27 had significant anticancer effects against human breast cancer and it may potentially be used as a novel anticancer agent for the treatment of breast cancer.
AB - We have previously reported that Gen-27, a newly synthesized flavonoid, exhibits anticancer effects against human colorectal cancer cells. In this study, we investigated the anticancer effects in human breast cancer cell lines and its underlying mechanisms. We demonstrated that Gen-27 inhibited the growth and proliferation of human breast cancer cells in concentration and time-dependent manners. It was found that Gen-27 induced mitochondrial-mediated apoptosis, characterized by the dissipation of mitochondrial membrane potential (ΔΨm), cytochrome c (Cyt c) release from mitochondria to cytosol, activation of caspases and induction of poly (ADP-ribose) polymerase (PARP). In addition, Gen-27 inhibited the glycolysis in human breast cancer cells. After treatment with Gen-27, the expression of HKII was down-regulated, accompanied by weakened interaction of HKII and VDAC. Further research revealed that the induction of mitochondrial apoptosis was associated with the decrease of HKII expression by Gen-27. Finally, in vivo studies demonstrated that Gen-27 significantly suppressed the growth and promoted apoptosis of MDA-MB-231 breast cancer orthotopic tumors with low systemic toxicity. In conclusion, the results showed that Gen-27 had significant anticancer effects against human breast cancer and it may potentially be used as a novel anticancer agent for the treatment of breast cancer.
KW - Apoptosis
KW - Breast cancer
KW - Gen-27
KW - Glycolysis
KW - HKII
KW - Mitochondria
UR - http://www.scopus.com/inward/record.url?scp=85006483266&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2016.11.001
DO - 10.1016/j.bcp.2016.11.001
M3 - Article
C2 - 27818240
AN - SCOPUS:85006483266
SN - 0006-2952
VL - 125
SP - 12
EP - 25
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
ER -