Nitidine chloride inhibited the expression of S phase kinase-associated protein 2 in ovarian cancer cells

Abstract

Nitidine chloride (NC) has been reported to exert its anti-tumor activity in various types of human cancers. However, the molecular mechanism of NC-mediated tumor suppressive function is largely unclear. In the current study, we used several approaches such as MTT, FACS, RT-PCR, Western blotting analysis, invasion assay, transfection, to explore the molecular basis of NC-triggered anti-cancer activity. We found that NC inhibited cell growth, induced cell apoptosis, caused cell cycle arrest in ovarian cancer cells. Emerging evidence has demonstrated that Skp2 plays an important oncogenic role in ovarian cancer. Therefore, we also explored whether NC exerts its biologic function via downregulation of Skp2 in ovarian cancer cells. We observed that NC significantly inhibited the expression of Skp2 in ovarian cancer cells. Notably, overexpression of Skp2 abrogated the anti-cancer activity induced by NC in ovarian cancer cells. Consistently, downregulation of Skp2 expression enhanced the sensitivity of ovarian cancer cells to NC treatment. Thus, inactivation of Skp2 by NC could be a novel strategy for the treatment of human ovarian cancer.

Antitumor functions and mechanisms of nitidine chloride in human cancers

“…Skp2 as an oncoprotein is the key adaptor of the SCF type of E3 ligase [35][36][37]. NC was reported to inhibit the Skp2 level in OC cells, while Skp2 upregulation abolished NC-induced antitumor property [38]. Thus, suppression of Skp2 expression level by NC might be a useful approach for management of OC patients [38].…”

“…NC was reported to inhibit the Skp2 level in OC cells, while Skp2 upregulation abolished NC-induced antitumor property [38]. Thus, suppression of Skp2 expression level by NC might be a useful approach for management of OC patients [38]. There is one study showing that NC blocked cell migratory and invasive activity through downregulation of MMP-2 as well as MMP-9 via suppression of ERK pathway in OC cells [39].…”

S-phase kinase-associated protein 2 is involved in epithelial-mesenchymal transition in methotrexate-resistant osteosarcoma cells

“…Recently, compound 25, a novel Skp2 inhibitor, was shown to exhibit potent antitumor activities and to cooperate with chemotherapeutic agents to suppress cancer cell survival ( 61 ). Several natural compounds have been reported to exert their antitumor activities via the inhibition of Skp2 expression in human cancers ( 62 – 64 ). It is important to note that natural compounds do not specifically inhibit Skp2.…”

Nitidine chloride represses Mcl‐1 protein via lysosomal degradation in oral squamous cell carcinoma

“…NC, one of the natural products, has also been studied to play an important role in the inhibition of cell proliferation in various cancers. For examples, NC triggers apoptosis and cell cycle arrest in ovarian cancer cells via suppression of S phase kinase‐associated protein 2 (Skp2) and inhibits malignant behavior of the human glioblastoma cells by targeting PI3K/AKT/mTOR signaling pathway . Zhai et al have reported the apoptotic activity of NC in colorectal cancer cells by regulating ERK signaling pathway.…”