Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells

Abstract

Studies have investigated the tumor suppressive role of rottlerin in carcinogenesis. However, the molecular mechanisms of rottlerin-induced anti-tumor activity are largely unclear. Skp2 (S-phase kinase associated protein 2) has been validated to play an oncogenic role in a variety of human malignancies. Therefore, inactivation of Skp2 could be helpful for the treatment of human cancers. In the current study, we explore whether rottlerin could inhibit Skp2 expression, leading to inhibition of cell growth, migration and invasion in breast cancer cells. We found that rottlerin treatment inhibited cell growth, induced apoptosis and cell cycle arrest. We also revealed that rottlerin suppressed cell migration and invasion in breast cancer cells. Mechanically, we observed that rottlerin significantly down-regulated the expression of Skp2 in breast cancer cells. Importantly, overexpression of Skp2 abrogated rottlerin-mediated tumor suppressive activity, whereas down-regulation of Skp2 enhanced rottlerin-triggered anti-tumor function. Strikingly, we identified that rottlerin exhibited its anti-tumor potential partly through inactivation of Skp2 in breast cancer. Our findings indicate that rottlerin could be a potential safe agent for the treatment of breast cancer.

Paeoniflorin inhibits cell viability and invasion of liver cancer cells via inhibition of Skp2

“…Curcumin has been demonstrated to inhibit the expression of Skp2 in several human cancer types (17,38,39). Rottlerin exhibited its anti-tumor activity by the inhibition of Skp2 in breast cancer and pancreatic cancer cells (18,40). The present study demonstrated that PF inhibited Skp2 expression in liver cancer cells.…”

“…The following thermocycling conditions were used for qPCR: Initial denaturation at 95˚C for 10 min; 45 cycles of 95˚C for 15 sec, 60˚C for 1 min; and a final extension at 72˚C for 5 min. Relative expression levels were quantified using the 2 -ΔΔCq method as previously described (18,19), and normalized to the internal reference gene GAPDH.…”

Dioscin: A new potential inhibitor of Skp2 for cancer therapy

“…A study reported that quercetin, curcumin and lycopene downregulated Skp2 expression, leading to promotion of cell cycle arrest in breast cancer cells [5]. Rottlerin, a polyphenolic substance in the fruits of mallotus philippinensis, exerts its anticancer activity via the suppression of Skp2 in breast and pancreatic cancer cells [6,7]. Nitidine chloride, a bioactive phytochemical alkaloid, was found to repress the expression of Skp2 in ovarian cancer cells.…”

Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma

“…Cells (3x10 5 cells/well) were cultured in a 6-well plate overnight and treated with the various concentrations of rottlerin for 48 h. Following treatment, the cells were harvested and washed with PBS, resuspended (1x10 5 cells) in 500 µl binding buffer with 5 µl propidium iodide (PI) and 5 µl FITC-conjugated anti-Annexin V antibody. Apoptosis was analyzed on a flow cytometer (BD Biosciences, Franklin Lakes, NJ, USA) as described previously (18).…”

“…The cells were incubated with 0.1 mg/ml RNase I and 50 mg/ml PI at 37˚C for 30 min. Cell cycle was analyzed on a flow cytometer (BD Biosciences) as described previously (18).…”