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

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.

The herbal extract deriving from aerial parts of Scutellaria baicalensis shows anti-inflammation and anti-hypoxia responses in cultured fin cells from rabbit fish

“…Several Chinese herbal extracts have been applied in aquaculture feedings to strength fish's immunity and to promote growth [ 25 ]. Scutellaria Radix (the dried root of S. baicalensis ) has been used as a Chinese medicine for centuries in China and Asia, and this herb is well-known to have multiple pharmacological activities, including anti-inflammation [ 11 ] and anti-hypoxia [ 26 ]. Recently, the extract of Scutellaria Radix was shown to inhibit the infection of SARS-CoV-2 virus [ 27 ].…”

Network Pharmacology and Bioinformatics Approach Reveals the Therapeutic Mechanism of Action of Baicalein in Hepatocellular Carcinoma

“…S. baicalensis is a skullcap plant native to several East Asian countries and Russia, and it is cultivated in many European countries. This plant has been widely used in traditional Chinese medicine since about 200–250 AD for the clinical treatment of hypertension, atherosclerosis, dysentery, common colds, inflammatory disorders, and tumors [26–28]. Baicalein is a major bioactive flavone derived from the dry roots of S. baicalensis .…”

Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro

“…The increased mitogenic signaling pathways of PI3K/AKT and MEK/ERK result in continued chronic proliferation in cancer cells [44][45][46][47]. We previously reported the activation of PI3K/AKT, MEK/ERK in cancer cells [48]. The AKT/ERK activation is a sign of malignancy and chemo-resistance in many types of cancers [44,45].…”