A novel antitumor activity of deguelin targeting the insulin-like growth factor (IGF) receptor pathway via up-regulation of IGF-binding protein-3 expression in breast cancer.
In this study, we investigated the antitumor effects of deguelin in several human breast cancer cells in vitro and in vivo. Deguelin inhibited cell viability and the anchorage-dependent and anchorage-independent colony formation of triple-negative (MDA-MB-231 and MDA-MB-468) and triple-positive (MCF-7) breast cancer cells, and it significantly reduced the growth of MCF-7 cell xenograft tumors. The induction of apoptosis, inhibition of insulin-like growth factor-1 receptor (IGF-1R) signaling activation, and up-regulation of IGF-binding protein-3 (IGFBP-3) expression may be associated with deguelin-mediated antitumor effects. Our findings suggest a potential therapeutic use for deguelin in patients with triple-negative breast cancer and for those with breast cancers who are sensitive to endocrine- and HER2-targeted therapies.
Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
Young-Ah
YA
Suh
Jai-Hyun
JH
Kim
Myung A
MA
Sung
Hye-Jin
HJ
Boo
Hye Jeong
HJ
Yun
Sun-Hye
SH
Lee
Hyo-Jong
HJ
Lee
Hye-Young
HY
Min
Young-Ger
YG
Suh
Kyu-Won
KW
Kim
Ho-Young
HY
Lee
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D034622:RNA Interference; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000378:metabolism*; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D000077022:Survivin; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D017451:Receptors, Somatomedin; D012402:Rotenone; D000077022:Survivin; C107489:BIRC5 protein, human; C515497:IGFBP3 protein, human; C508053:ERBB2 protein, human; C107676:deguelin