Genistein inhibits the S‑phase kinase‑associated protein 2 expression in breast cancer cells

Abstract

Abstract. Breast cancer is one of the most lethal cancers affecting women worldwide and was estimated to account for ~30% of all new cancer diagnoses in women. Although available evidence has proved the tumor suppressor role of genistein in cancer, the underling mechanisms have remained to be fully elucidated. S-phase kinase-associated protein 2 (Skp2) has been revealed to critically enhance the pathogenesis of multiple human cancers. The present study determined whether genistein exerts its anti-tumor function by suppressing Skp2 in breast cancer cells. Genistein significantly inhibited the proliferation, invasion and migration of breast cancer cells. Furthermore, genistein treatment also induced marked apoptosis and a typical cell cycle arrest in G2/M phase. Mechanistically, genistein treatment was identified to cause a significant downregulation of Skp2. Two crucial tumor suppressors, p21 and p27, were upregulated in genistein-treated breast cancer cells. The present results revealed that genistein exerted its tumor suppressor effect at least partially via inhibition of Skp2 and promotion of its downstream targets p21 and p27. Therefore, inactivation of Skp2 by genistein may be a promising approach for breast cancer treatment.

In vitro study of the antioxidative and antiproliferative capabilities of Lactobacillus casei 16‐fermented soymilk

“…Both the water extract and the ethanol extract of the L. casei 16-fermented soymilk could enhance the survival rates and the SOD activities of the ABAP-damaged HepG 2 cells. Ye, Li, and Wei (2017) determined that genistein exerted its tumor suppressor effect at least partially via inhibition of S-phase kinase-associated protein 2 and promotion of its downstream targets p21 and p27 in breast cancer cells. It can be concluded that the aglycone isoflavones, total phenolics, and free amino acids in the L. casei and HT-29 cells, and the ethanol extract exhibited the higher antiproliferative activity.…”

Expression and correlation of miR‑124 and miR‑126 in breast cancer

“…Currently, clinical studies (14) have confirmed that the pathogenesis of BC is related to a variety of factors, such as the endocrine regulation in patients, familial inheritance, benign breast lesions, malignant transformation of BC and geographical environment (15). In the biological study on cancer-related genes in recent years, researchers have focused on protein genes (16), such as S-phase kinase-associated protein 2 (SKP2) (p45). A kind of small non-coding RNA, miRNA, directly related to tumorigenesis has been found recently, which, as an important regulatory factor for tumors, is involved in the occurrence, development, invasion and metastasis of tumor.…”

Bioactive Compounds: Multi-Targeting Silver Bullets for Preventing and Treating Breast Cancer

“…This study showed that genistein administration can potentially prevent the progression of DCIS to invasive ductal carcinoma. Invasion and migration are important characteristics of an invasive cancer and genistein blocks invasion and migration of breast cancer cells by inhibiting S-phase kinase-associated protein 2 (Skp2), which is an important kinase frequently upregulated in multiple cancers [179]. Combined treatment with genistein and doxorubicin increases intracellular buildup of doxorubicin and increases efficacy of chemotherapy [180,181].…”