TY - JOUR
T1 - A flavonoid chrysin suppresses hypoxic survival and metastatic growth of mouse breast cancer cells
AU - Lirdprapamongkol, Kriengsak
AU - Sakurai, Hiroaki
AU - Abdelhamed, Sherif
AU - Yokoyama, Satoru
AU - Maruyama, Takeyuki
AU - Athikomkulchai, Sirivan
AU - Viriyaroj, Amornrat
AU - Awale, Suresh
AU - Yagita, Hideo
AU - Ruchirawat, Somsak
AU - Svasti, Jisnuson
AU - Saiki, Ikuo
PY - 2013/11
Y1 - 2013/11
N2 - Tumor hypoxia commonly occurs in solid tumors, and correlates with metastasis. Current cancer therapies are inefficient in curing metastatic disease. Herein, we examined effect of Thai propolis extract and its major constituent, chrysin, on hypoxic survival of 4T1 mouse breast cancer cells in vitro, and investigated its underlying mechanism. In vivo effect of chrysin on metastatic progression of cancer cells was studied, both as a single agent and in combination with another antimetastatic agent, agonistic monoclonal antibody targeting the DR5 TRAIL receptor (DR5 mAb). Thai propolis extract and chrysin decreased survival of 4T1 cells after exposure to hypoxia (1% O2), for 2 days. Immunoblot analysis revealed that chrysin inhibited hypoxia-induced STAT3 phosphorylation without affecting HIF-1α protein level. Chrysin also abrogated hypoxia-induced VEGF gene expression as determined by qRT-PCR. The in vivo effect of chrysin was determined in a spontaneous metastasis mouse model of breast cancer, either alone or in combination with DR5 mAb. Daily oral administration of chrysin in Balb/c mice implanted with 4T1 cells significantly suppressed growth of lung metastatic colonies. Moreover, antimetastatic activity of DR5 mAb was enhanced when given in combination with chrysin. We demonstrate that chrysin has potential in controlling metastatic progression.
AB - Tumor hypoxia commonly occurs in solid tumors, and correlates with metastasis. Current cancer therapies are inefficient in curing metastatic disease. Herein, we examined effect of Thai propolis extract and its major constituent, chrysin, on hypoxic survival of 4T1 mouse breast cancer cells in vitro, and investigated its underlying mechanism. In vivo effect of chrysin on metastatic progression of cancer cells was studied, both as a single agent and in combination with another antimetastatic agent, agonistic monoclonal antibody targeting the DR5 TRAIL receptor (DR5 mAb). Thai propolis extract and chrysin decreased survival of 4T1 cells after exposure to hypoxia (1% O2), for 2 days. Immunoblot analysis revealed that chrysin inhibited hypoxia-induced STAT3 phosphorylation without affecting HIF-1α protein level. Chrysin also abrogated hypoxia-induced VEGF gene expression as determined by qRT-PCR. The in vivo effect of chrysin was determined in a spontaneous metastasis mouse model of breast cancer, either alone or in combination with DR5 mAb. Daily oral administration of chrysin in Balb/c mice implanted with 4T1 cells significantly suppressed growth of lung metastatic colonies. Moreover, antimetastatic activity of DR5 mAb was enhanced when given in combination with chrysin. We demonstrate that chrysin has potential in controlling metastatic progression.
KW - Antimetastatic
KW - Hypoxia
KW - Natural products
KW - Propolis
KW - STAT3
UR - http://www.scopus.com/inward/record.url?scp=84885052665&partnerID=8YFLogxK
U2 - 10.3892/or.2013.2667
DO - 10.3892/or.2013.2667
M3 - 学術論文
C2 - 23969634
AN - SCOPUS:84885052665
SN - 1021-335X
VL - 30
SP - 2357
EP - 2364
JO - Oncology Reports
JF - Oncology Reports
IS - 5
ER -