The differential susceptibilities of MCF-7 and MDA-MB-231 cells to the cytotoxic effects of curcumin are associated with the PI3K/Akt-SKP2-Cip/Kips pathway

Abstract

Background: The mechanism underlying the differential cytotoxicity of curcumin in various cancer types, however, remains largely unclear. The aims of this study is to examine the concentration-and time-related effects of curcumin on two different breast cancer cells, MCF-7 and MDA-MB-231, and investigated the functional changes induced by curcumin treatment, as well as their relationship to the PI3K/Akt-SKP2-Cip/Kips pathway. Methods: First, WST-1 and clonogenic assay were performed to determine the cytotoxicity of curcumin in MCF-7 and MDA-MB-231 cells. Then, the expression of CDK interacting protein/Kinase inhibitory protein (Cip/Kips) members (p27, p21 and p57) and S-phase kinase-associated protein-2 (SKP2) was investigated by QRT PCR and Western Blotting. Curcumin's effect on PI3K (phosphatidylinositol 3-kinase) /Akt and its substrates Foxo1 and Foxo3a were then studied by Western Blotting. Small interfering RNAs (siRNAs) targeting SKP2 was used to explore the relationship between SKP2 and Cip/Kips members. Finally, WST-1 assay was tested to explore the concomitant treatment with curcumin and the inhibition of PKB or SKP2 signaling on curcumin sensitivity in MCF-7 and MDA-MB-231 cells.

Inhibition of Skp2 suppresses the proliferation and invasion of osteosarcoma cells

“…Quercetin, curcumin and lycopene enhanced cell cycle arrest via the targeting of Skp2 expression in breast cancer cells (54). Moreover, curcumin was validated to regulate the PI3K/Akt-SKP2-Cip/Kips pathway in breast cancer cells (55,56). Furthermore, curcumin inhibited tumorigenesis via the downregulation of Skp2 in glioma cells (58).…”

“…Caffeic acid phenethyl ester suppressed cell proliferation and arrested the cell cycle through inactivation of Skp2 in prostate cancer cells (53). Notably, multiple natural agents have been characterized as Skp2 inhibitors (53)(54)(55)(56). Flavokawain A (FKA) selectively inhibited Skp2 in a proteasome-dependent manner in prostate cancer (57).…”

Recent advances of curcumin and its analogues in breast cancer prevention and treatment

“…There is a difference in the function of the p13k/Akt-SKP2 pathway of the two cell lines in response to curcumin, highlighting the differential susceptibility of the breast cancer cells to curcumin’s cytotoxic effects. 98 A study of the effectiveness of curcumin’s anti-invasive ability to inhibit morphological changes triggered by lipolysaccharide (LPS) in MCF-7 and MDA-MB-231 cells revealed NF-κB-Snail pathway inactivation mediates suppression and increase of LPS-induced EMT markers vimentin and E-cadherin respectively. 99 Sood et al, 100 performed an investigation of human breast cell carcinogenesis induced by triclocarban (TCC) and the use of curcumin as a preventive agent in MCF10A and MCF-7 breast cancer cell lines.…”

Nanostructured lipid carriers enhance the bioavailability and brain cancer inhibitory efficacy of curcumin both in vitro and in vivo

“…Due to its pharmacological effects, recently many researches have focused on its antioxidant, anti-inflammatory and anti-tumorigenic properties (Bandyopadhyay, 2014;Vecchi Brumatti et al, 2014;El-Bahr, 2015;Shanmugam et al, 2015). Numerous works prove that cur exerts strong anticancer effects against a far ranging of human cancer cells, including breast cancer, lung cancer and HCC (Jia et al, 2014;Chen et al, 2015;Guo et al, 2015). The mechanisms of the anticancer efficiency of cur are also revealed as the remarkable inhibitive effect on nuclear factor (NF-kB) activity and the downregulation of NF-kB regulated gene products, including prostaglandin E2, cyclooxygenase (COX)-2 and IL-8 (Su et al, 2006(a); Wang et al, 2006;Chiang et al, 2014).…”