Inhibition of silibinin on migration and adhesion capacity of human highly metastatic breast cancer cell line, MDA-MB-231, by evaluation of β1-integrin and downstream molecules, Cdc42, Raf-1 and D4GDI

Abstract

Metastasis is a property of malignant cancer cells that requires integrins which with their downstream molecules participate in a number of signaling events in cells with pivotal roles in malignancy, migration and invasion of tumor cells. Silibinin, a flavonoid antioxidant from milk thistle (Silybum marianum L.), has attracted attention in the last decades for chemoprevention and chemotherapy of tumor cells. In the present study, the effect of silibinin on migration and adhesion capacity of MDA-MB-231 cells, a highly metastatic human breast cancer cell line, was investigated by evaluation of β1-integrin and its important downstream molecules. MTT, migration and adhesion assays were performed to evaluate the silibinin effects on proliferation, migration and adhesion of MDA-MB-231 cells. In addition, the influence of the silibinin on the expression of β1-integrin, Raf-1, Cdc42 and D4-GDI mRNAs was assessed by RT-PCR. Results showed significant dose-dependent inhibitory effect of silibinin on proliferation, migration and adhesion of MDA-MB-231 cells. It significantly inhibited the expression of Cdc42 and D4-GDI mRNAs but had no statistically significant effect on the expression of β1-integrin and Raf-1 mRNAs although it indirectly but effectively modulated β1-integrin signaling pathway and RAF1 function. In conclusion, the results showed the silibinin effectson reducing the rate of metastasis, migration and adhesion of MDA-MB-231 to distant organs.

A Presurgical Study of Oral Silybin-Phosphatidylcholine in Patients with Early Breast Cancer

“…Silybin modulates imbalance in cellular homeostasis through interference with the expressions of cell-cycle regulators and proteins involved in apoptosis (15). Silybin also showed antiinflammatory (16) as well as antimetastatic activity (17), and synergistic effects with doxorubicin and cisplatin in both estrogen-dependent and independent human breast carcinoma cells (18). However, quantitative data on human breast tissue levels of silybin are absent, thus hampering the understanding of the biologic activities of this compound in breast cancer prevention and treatment.…”

Silibinin, up-regulates chemokine receptor expression in MDA-MB-231 breast cancer cell line

“…Data are expressed as mean ±SD. .Moreover, in another study, Dastpeymanet al in 2012 showed significant dose-dependent inhibitory effect of silibinin on proliferation, migration and adhesion of MDA-MB-231 cells 14 . However, in this study, silibinin showed not only a dose-dependent but alsoa timedependent inhibitory effect on MDA-MB-231 cell proliferation.…”

“…In the last decades silibininhas attracted attention for chemoprevention and chemotherapy of tumor cells. Silibinincanalso exert the significant anti-neoplastic effects in a variety of in vitro and in vivo epithelial cancer models, including breast, lung, skin, prostate, bladder, colon and kidney carcinomas 14,15 . In the present study, the effect of silibinin on expression of chemokine receptors CXCR3, CCR5 and CCR7 in MDA-MB-231 cells, a highly metastatic human breast cancer cell line, was investigated by Real-Time PCR.…”

Dendrosomal Curcumin Inhibits Metastatic Potential of Human SW480 Colon Cancer Cells through Down-regulation of Claudin1, Zeb1 and Hef1-1 Gene Expression

“…After 5 min of crystal violet staining (0.1% (w/v) in 25% (v/v) methanol) at room temperature, the cells were gently rinsed five times with water to remove unbound stain and allowed to air-dry at room temperature. Fixed cells were lysed by 0.2% Triton X-100, and the absorbance was measured at 550 nm as follows: % Adhesion to matrix in 0 µM of DNC as 100 (Dastpeyman et al, 2012).…”