RETRACTED: Daidzein exerts anticancer activity towards SKOV3 human ovarian cancer cells by inducing apoptosis and cell cycle arrest, and inhibiting the Raf/MEK/ERK cascade (Retracted article. See vol. 47, 2021)

Ovarian cancer is the main cause of gynecological cancer-associated mortality around the world. Despite initial responses to chemotherapy, frequent relapse occurs. Daidzein is an important flavonoid and has been shown to exhibit a diversity of pharmacological properties, including antimicrobial and anticancer activities. However, information on the anticancer activity of daidzein against ovarian cancer remains limited. Therefore, the present study evaluated the anticancer activity of daidzein against a panel of human ovarian cancer cell lines and one normal ovarian cell line (Moody). The results revealed that daidzein exhibited potent anticancer activity against SKVO3 cells with a half-maximal inhibitory concentration (IC50) of 20 M. However, it exhibited comparatively lower activity against normal ovarian Moody cells, which had an IC50 of 100 M. Daidzein induced morphological changes in SKOV3 cells and mitochondrial apoptosis, as evident from DAPI, AO/EB and Annexin V/propidium iodide staining. This was associated with the upregulation of B-cell lymphoma 2-associated X protein, cytochrome c, cleaved caspase-3 and -9, and cleaved poly (ADP-ribose) polymerase. Daidzein also triggered G2/M cell arrest through the downregulation of pCdc25c, Cdc25c, pCdc2, Cdc2 and cyclin B1. The effect of daidzein on the migration of SKOV3 cells was also determined, the results of which indicated that daidzein inhibited cell migration in a concentration-dependent manner and was coupled with concomitant decrease in the expression of matrix metalloproteinase (MMP)-2 and -9. Additionally, daidzein-inhibited cell growth was simultaneous with suppression of the expression of phosphorylated mitogen-activated protein kinase kinase and phosphorylated extracellular signal-regulated kinase. The present study also examined whether daidzein exerts similar activity against SKOV3 cells in nude mouse xenograft models and it was revealed that daidzein considerably reduced the tumorigenesis in vivo, indicative of the potential for daidzein as a lead molecule in the development of ovarian cancer chemotherapy