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Scutellaria baicalensis targets the hypoxia‐inducible factor‐1α and enhances cisplatin efficacy in ovarian cancer
Author(s) -
Hussain Imran,
Waheed Sana,
Ahmad Kashif A.,
Pirog John E.,
Syed Viqar
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27063
Subject(s) - ly294002 , cancer research , ovarian cancer , scutellaria baicalensis , cisplatin , cancer cell , protein kinase b , mapk/erk pathway , angiogenesis , pi3k/akt/mtor pathway , mg132 , pharmacology , kinase , chemistry , proteasome inhibitor , cell culture , medicine , cancer , biology , microbiology and biotechnology , signal transduction , chemotherapy , traditional chinese medicine , pathology , alternative medicine , genetics
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.