Hwanggeumchal sorghum induces cell cycle arrest, and suppresses tumor growth and metastasis through Jak2/STAT pathways in breast cancer xenografts.
BACKGROUND
Cancer is one of the highly virulent diseases known to humankind with a high mortality rate. Breast cancer is the most common cancer in women worldwide. Sorghum is a principal cereal food in many parts of the world, and is critical in folk medicine of Asia and Africa. In the present study, we analyzed the effects of HSE in metastatic breast cancer.


RESULTS
Preliminary studies conducted on MDA-MB 231 and MCF-7 xenograft models showed tumor growth suppression by HSE. Western blotting studies conducted both in vivo and in vitro to check the effect of HSE in Jak/STAT pathways. Anti-metastatic effects of HSE were confirmed using both MDA-MB 231 and MCF-7 metastatic animal models. These studies showed that HSE can modulate Jak/STAT pathways, and it hindered the STAT5b/IGF-1R and STAT3/VEGF pathways not only by down-regulating the expression of these signal molecules and but also by preventing their phosphorylation. The expression of angiogenic factors like VEGF, VEGF-R2 and cell cycle regulators like cyclin D, cyclin E, and pRb were found down-regulated by HSE. In addition, it also targets Brk, p53, and HIF-1α for anti-cancer effects. HSE induced G1 phase arrest and migration inhibition in MDA-MB 231 cells. The metastasis of breast cancer to the lungs also found blocked by HSE in the metastatic animal model.


CONCLUSIONS
Usage of HS as a dietary supplement is an inexpensive natural cancer therapy, without any side effects. We strongly recommend the use of HS as an edible therapeutic agent as it possesses tumor suppression, migration inhibition, and anti-metastatic effects on breast cancer.
Department of Pathology, School of Medicine, and Institute of Biomedical Science and Technology, Konkuk University Glocal Campus, Seoul, South Korea.
Jin Hee
JH
Park
Pramod
P
Darvin
Eun Joung
EJ
Lim
Youn Hee
YH
Joung
Dae Young
DY
Hong
Eui U
EU
Park
Seung Hwa
SH
Park
Soo Keun
SK
Choi
Eon-Soo
ES
Moon
Byung Wook
BW
Cho
Kyung Do
KD
Park
Hak Kyo
HK
Lee
Myong-Jo
MJ
Kim
Dong-Sik
DS
Park
Ill-Min
IM
Chung
Young Mok
YM
Yang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000188:drug therapy; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D045868:Sorghum / Q000737:chemistry*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015513:Oncogene Proteins; D010936:Plant Extracts; D050791:STAT Transcription Factors; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D017526:Receptor, IGF Type 1; D053614:Janus Kinase 2