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J Cell Biochem. 2018 Sep;119(9):7515-7524. doi: 10.1002/jcb.27063. Epub 2018 May 24.

Scutellaria baicalensis targets the hypoxia-inducible factor-1α and enhances cisplatin efficacy in ovarian cancer.

Author information

1
Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
2
Carle Illinois College of Medicine, University of Illinois Urbana Champaign, Champaign, Illinois.
3
College of Health and Wellness, Acupuncture and Chinese Medicine Program, Northwestern Health Sciences University, Bloomington, Minnesota.
4
John P. Murtha Cancer Center at Walter Reed National Military Medical Center, Bethesda, Maryland.
5
Department of Molecular and Cell Biology, Uniformed Services University, Bethesda, Maryland.

Abstract

Hypoxia-inducible factor-1alpha (HIF-1α) is aberrantly upregulated in tumors and implicated in angiogenesis, metastasis, and drug resistance. Therefore, developing treatments that target HIF-1α may be a viable therapeutic approach. In Traditional Chinese Medicine (TCM), Scutellaria baicalensis (SB) is used for the treatment of cancer but the anti-cancer mechanisms are not known. We examined the effects of SB on HIF-1α expression in ovarian cancer (OC) cell lines grown under normoxic and hypoxic conditions. SB treatment attenuated HIF-1α expression in cancer cell lines. Treatment of cells with cycloheximide (CHX) reduced HIF-1α levels similar to cells treated with SB. Furthermore, SB-induced HIF-1α inhibition was abrogated by the proteasomal inhibitor MG132 and a lysosome inhibitor, chloroquine. Activation of PI3K/AKT and MAPK/ERK seen in OC cells was reduced with SB. Pretreatment of cells with LY294002 (phosphoinositide 3-kinase inhibitor) and PD98059 (mitogen-activated protein kinase inhibitor) reduced HIF-1α expression comparable to SB-treated cells. SB potentiated the anti-growth effects of cisplatin on OC cells by attenuating the expression of HIF-1α, ABCG1, and ABCG2. Taken together, the findings suggest that targeting HIF-1α with SB could be an effective treatment strategy for cancer and SB can improve the sensitivity of cancer cells to cisplatin, which is a major challenge in therapy for ovarian tumors.

KEYWORDS:

HIF-1α; PI3K/Akt; chemoresistance; hypoxia; tumor growth

PMID:
29797601
DOI:
10.1002/jcb.27063

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