title: Induction of apoptosis and growth arrest in human breast carcinoma cells by a snake (Walterinnesia aegyptia) venom combined with silica nanoparticles: crosstalk between Bcl2 and caspase 3.
abstract: We recently demonstrated that the snake venom extracted from Walterinnesia aegyptia (WEV) either alone or combined with silica nanoparticles (WEV+NP) enhanced the proliferation of mice immune cells and simultaneously decreased the proliferation of human breast carcinoma cell line (MDA-MB-231). However, the molecular mechanism of how this venom induced growth arrest of breast cancer cells has not been studied. In this context, we extended our study to evaluate the anti-tumor potential of WEV and WEV+NP on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as their effects on non-tumorigenic normal breast epithelial cells (MCF-10). The IC(50 )values of WEV alone and WEV+NP in these cell lines were determined to be 50 ng/ml and 20 ng/ml, respectively. Interestingly, at these concentrations, the venom did not affect the viability of normal MCF-10 cells and treatment of all these cell lines with NP alone did not affect their viability. Using annexin-V binding assay followed by flow cytometry analysis, we found that combination of WEV with NP strongly induced apoptosis in MDA-MB-231 and MCF-7 cancer cells without significant effect on normal MCF-10 cells. Furthermore, we found that WEV+NP decreased the expression of Bcl2 and enhanced the activation of caspase 3 in MDA-MB-231 and MCF-7 cells. Most importantly, WEV+NP-treated breast cancer cells, but not normal MCF-10 cells, exhibited a significant (P<0.05) reduction in actin polymerization and cytoskeletal rearrangement in response to CXCL12. Our data reveal biological effects of WEV or WEV+NP and the underlying mechanisms to fight breast cancer cells.
authors.affiliation: Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohamed K
authors.initials: MK
authors.lastname: Al-Sadoon
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: Abdel-Maksoud
authors.forename: Danny M
authors.initials: DM
authors.lastname: Rabah
authors.forename: Gamal
authors.initials: G
authors.lastname: Badr
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects; D004546:Elapid Venoms / Q000633:toxicity*; D017815:Elapidae / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000199:Actins; D054377:Chemokine CXCL12; D004546:Elapid Venoms; D019253:Proto-Oncogene Proteins c-bcl-2; D012822:Silicon Dioxide; D053148:Caspase 3