Background:

IC50: 2 μM

Hispidin is a protein kinase Cβ inhibitor.

Protein Kinase C (PKC), a serine/threonine kinase, is activated by signal transduction pathways producing DAG from phosphatidylinositol diphosphate and phosphatidylcholine via the action of various activated phospholipases. Protein kinase Cβ (PKCβ) plays a critical role in the initiation of colon carcinogenesis in a preclinical mouse model by promoting proliferation and increased β-catenin accumulation.

In vitro: In previous study hispidin was found to reduce cell viability in both mouse and human colon cancer cells, and the apoptotic cell morphological changes were also observed. These results showed accumulation of the sub-G1 cell population and increase in early apoptosis dose-dependently. Moreover, hispidin could induce apoptosis via up-regulation of both intrinsic and extrinsic apoptotic pathways. Although the molecular mechanism underlying hispidin-induced apoptosis was known to involve the generation of ROS, however hispidin was not able to display any apoptosis in the pre-treatment with N-acetyl-L-cysteine, a ROS scavenger [1].

In vivo: Previous animal study found that the treatment with PKC-activating agent phorbol-12-myristate-13-acetate could attenuate exendin-4-induced relaxations and reduced GLP-1R expression in Wistar-Kyoto rat arteries, which were reversed by hispidin [2].

Clinical trial: Up to now, hispidin is still in the preclinical development stage.

参考文献:
[1] Lim JH, Lee YM, Park SR, Kim DH, Lim BO.  Anticancer activity of hispidin via reactive oxygen species-mediated apoptosis in colon cancer cells. Anticancer Res. 2014 Aug;34(8):4087-93.
[2] Liu L, Liu J, Gao Y, Ng CF, Yu X, Dou D, Huang Y.  Protein kinase Cβ mediates downregulated expression of glucagon-like peptide-1 receptor in hypertensive rat renal arteries. J Hypertens. 2015 Apr;33(4):784-90; discussion 790.