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Title: A flavonoid chrysin suppresses hypoxic survival and metastatic growth of mouse breast cancer cells
Authors: Lirdprapamongkol K.
Sakurai H.
Abdelhamed S.
Yokoyama S.
Maruyama T.
Athikomkulchai S.
Viriyaroj A.
Awale S.
Yagita H.
Ruchirawat S.
Svasti J.
Saiki I.
Keywords: antimetastatic agent
antineoplastic agent
death receptor 5
hypoxia inducible factor 1alpha
monoclonal antibody
monoclonal antibody DR5
natural product
propolis extract
STAT3 protein
unclassified drug
animal cell
animal experiment
animal model
animal tissue
antineoplastic activity
breast cancer
cancer cell
cancer combination chemotherapy
cancer inhibition
cancer model
cell culture
cell hypoxia
cell strain
cell strain 4T1
cell survival
controlled study
drug effect
drug isolation
drug megadose
gene expression
in vitro study
in vivo study
lung metastasis
metastasis inhibition
primary tumor
priority journal
protein phosphorylation
VEGF gene
Breast Neoplasms
Cell Hypoxia
Cell Line, Tumor
Cell Proliferation
Cell Survival
Gene Expression Regulation, Neoplastic
Neoplasm Metastasis
Receptors, TNF-Related Apoptosis-Inducing Ligand
STAT3 Transcription Factor
Issue Date: 2013
Abstract: 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.
ISSN: 1021335X
Appears in Collections:Scopus 1983-2021

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