Alpinumisoflavone is a prenylated isoflavonoid derived from the Cudrania tricuspidate fruit and Genista pichisermolliana.
Alpinumisoflavone has anticancer properties in a variety of
cancer cells, including colorectal, esophageal, renal and
hepatocellular carcinoma. However, its mechanisms and effects in
ovarian cancer remain unexplored. Our findings indicate that
alpinumisoflavone triggers anti-proliferation in 2D- and 3D-cultured human
ovarian cancer (ES2 and OV90) cells, including a reduction in the
proliferating cell nuclear antigen expression and sub-G1 phase arrest of the cell cycle. Both
alpinumisoflavone-treated ES2 and OV90 cells exhibited an augmentation in late apoptotic cells and the depolarization of mitochondrial membrane potential (
MMP). We also observed a decrease in respiratory chain activity in
ovarian cancer cells, owing to lower energy output by the
alpinumisoflavone. In addition, combining
cisplatin (a chemotherapeutic drug used in several
malignancies) with
alpinumisoflavone boosted apoptosis in ES2 and OV90 cells via a reduction in cell proliferation, induction of late apoptotic cells, and depolarization of
MMP. Furthermore,
alpinumisoflavone also regulated the PI3K/AKT, MAPK and endoplasmic reticulum (ER) stress regulatory signaling pathways, leading to cell death in both ES2 and OV90 cells. In general, our findings verified that
alpinumisoflavone inhibited
ovarian cancer cell growth via mitochondrial malfunction.