Mangiferin inhibits cell migration and invasion through Rac1/WAVE2 signalling in breast cancer
- 153 Downloads
Breast tumour progression results from the advancement of the disease to a metastatic phenotype. Rac1 and Cdc42 belong to the Rho family of genes that, together with their downstream effectors, Wiskott–Aldrich Syndrome protein-family verprolin-homologous protein 2 (WAVE2) and Arp2/3, assume a vital part in cytoskeletal rearrangement and the arrangement of film projections that advance malignant cell relocation and invasion. Mangiferin is a characteristic polyphenolic compound from Mangifera indica L. (Anacardiaceae), ordinarily referred to as mango, that is consumed worldwide as a natural product, including culinary and seasoning applications. Mangiferin delays breast malignancy development and progression by inhibiting different signalling pathways required in mitogenic signalling and metastatic progression. Studies were performed to analyse the impact of mangiferin on Rac1/WAVE2 flagging, relocation and invasion in highly metastatic human MDA-MB-231 mammary cells. Additional studies led to the observation that comparative treatment with mangiferin caused marked reduction in tumour cell movement and invasion. Taken together, these discoveries demonstrate that mangiferin treatment adequately hinders Rac1/WAVE2 flagging and diminishes metastatic phenotypic expression in malignant mammary cells, indicating that mangiferin may provide a benefit as a novel restorative approach in the treatment of metastatic breast cancer.
KeywordsMigration Invasion Mangiferin Rac1 Wiskott–Aldrich Syndrome protein-family verprolin-homologous protein 2 (WAVE2)
- Cheng P, Peng ZG, Yang J, Song SJ (2007) The effect of mangiferin on telomerase activity and apoptosis in leukemic K562 cells. Zhong Yao Cai 30:306–309Google Scholar
- Lucato CM, Halls ML, Ooms LM, Liu HJ, Mitchell CA, Whisstock JC et al (2015) The phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac exchanger 1.Ras-related C3 botulinum toxin substrate 1 (P-Rex1.Rac1) complex reveals the basis of Rac1 activation in breast cancer cells. J Biol Chem 290:20827–20840CrossRefGoogle Scholar
- Rajendran P, Jayakumar T, Nishigaki I, Ekambaram G, Nishigaki Y, Vetriselvi J et al (2013) Immunomodulatory effect of mangiferin in experimental animals with benzo(a)pyrene-induced lung carcinogenesis. Int J Biomed Sci IJBS 9:68–74Google Scholar
- Takenawa T, Miki H (2001) WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J Cell Sci 114:1801–1809Google Scholar