Biochanin A inhibits endothelial cell functions and proangiogenic pathways

Abstract

Malignant gliomas, such as glioblastoma multiforme, are highly vascularized tumors of the central nervous system. A rich network of angiogenic vessels supporting glioma growth is an important therapeutic target in glioma therapy. In the past few years, small molecules have gained interest as multitargeting therapies for cancer. Biochanin A is a small, natural dietary isoflavone known for its anticancer potential. Previously, we have found that biochanin A inhibits invasion in human glioblastoma cells. In this study, we elucidated the antiangiogenic mechanisms of biochanin A using rat brain tumor (C6) and murine brain endothelial (bEnd.3) cells and an ex-vivo chick chorioallantoic membrane model. Biochanin A inhibited endothelial cell functions such as cell viability, migration, and invasion, as analyzed using MTT, scratch wound, and gelatin zymography assays. Activation of proangiogenic proteins (ERK/AKT/mTOR) was inhibited. Biochanin A also inhibited chemical hypoxia-inducible factor-1α and vascular endothelial growth factor in C6 cells. Results of chick chorioallantoic membrane assay showed that biochanin A inhibited blood vessel formation ex vivo. As these results suggest that biochanin A directly targets different facets of angiogenesis in vitro and ex vivo, this study provides a rationale for future preclinical evaluation of its efficacy against angiogenic gliomas.

Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α

“…Gliomas are serious primary brain tumors, which account for 80% of malignant tumors of the central nervous system in the United States. Current therapeutic strategies for this type of brain cancer are inadequate and the median survival rate for patients with malignant glioma is 14 months due to their aggressive nature, high recurrence rate, and gradual increase in radiotherapy and chemotherapy resistance ( 1 ). Therefore, it is vital to examine the mechanisms underlying the progression of glioma and to urgently develop novel therapies with improved therapeutic effects for the treatment of patients with glioma.…”

Recent trends in preclinical drug–drug interaction studies of flavonoids — Review of case studies, issues and perspectives

“…() showed significant anti‐cancer efficacy of silibinin and proposed chemical modifications to enable it to impart potent anti‐cancer efficacy; (ii) Biochanin A: Jain et al . () proposed the use of biochanin A in gliomas because it inhibited proangiogenic pathways, vascular endothelial growth factor and chemical hypoxia inducible factor in their preclinical investigation; (iii) Baicalin: In this report, baicalin showed inhibition of both superoxide dismutase (SOD) and hypoxia inducible factor‐1 (HIF‐1), and hence there was a potential to be used in lung carcinoma and lung metastasis where both SOD and HIF‐1 pathways are prevalent (Du et al ., ).…”

“…Another consideration that may be important in the selection of the flavonoid could also be the potential effect of the chosen flavonoid to independently demonstrate anti-cancer potential either in a preclinical, in vitro or clinical setting. Examples include: (i) Silibinin: Agarwal et al (2013) showed significant anti-cancer efficacy of silibinin and proposed chemical modifications to enable it to impart potent anti-cancer efficacy; (ii) Biochanin A: Jain et al (2015) proposed the use of biochanin A in gliomas because it inhibited proangiogenic pathways, vascular endothelial growth factor and chemical hypoxia inducible factor in their preclinical investigation; (iii) Baicalin: In this report, baicalin showed inhibition of both superoxide dismutase (SOD) and hypoxia inducible factor-1 (HIF-1), and hence there was a potential to be used in lung carcinoma and lung metastasis where both SOD and HIF-1 pathways are prevalent (Du et al, 2010).…”

Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630

“…In addition, owing to the structural similarities between BCA and estrogen, BCA can exert both estrogenic and anti-estrogenic effects 4 and is marketed for the treatment of inflammation, 5,6 osteoporosis, 7,8 and other diseases. 9,10 However, its clinical efficacy is limited by its low oral bioavailability, which is due to poor water solubility, high clearance, and large apparent volume of distribution. 11 Hence, new delivery systems are required to improve the performance of BCA.…”