Snake (Walterinnesia aegyptia) venom-loaded silica nanoparticles induce apoptosis and growth arrest in human prostate cancer cells
- 833 Downloads
Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The progression and invasion of PCa are normally mediated by the overexpression of chemokine receptors (CKRs) and the interaction between CKRs and their cognate ligands. We recently demonstrated that venom extracted from Walterinnesia aegyptia (WEV) either alone or in combination with silica nanoparticles (WEV+NP) mediated the growth arrest and apoptosis of breast cancer cells. In the present study, we evaluated the impact of WEV alone and WEV+NP on the migration, invasion, proliferation and apoptosis of prostate cancer cells. We found that WEV alone and WEV+NP decreased the viability of all cell types tested (PCa cells isolated from patient samples, PC3 cells and LNCaP cells) using an MTT assay. The IC50 values were determined to be 10 and 5 μg/mL for WEV alone and WEV+NP, respectively. WEV+NP decreased the surface expression of the CKRs CXCR3, CXCR4, CXCR5 and CXCR6 to a greater extent than WEV alone and subsequently reduced migration and the invasion response of the cells to the cognate ligands of the CKRs (CXCL10, CXCL12, CXCL13 and CXCL16, respectively). Using a CFSE proliferation assay, we found that WEV+NP strongly inhibited epidermal growth factor-mediated PCa cell proliferation. Furthermore, analysis of the cell cycle indicated that WEV+NP strongly altered the cell cycle of PCa cells and enhanced the induction of apoptosis. Finally, we demonstrated that WEV+NP robustly decreased the expression of anti-apoptotic effectors, such as B cell Lymphoma-2 (Bcl-2), B cell Lymphoma-extra large (Bcl-XL) and myeloid cell leukemia sequence-1 (Mcl-1), and increased the expression of pro-apoptotic effectors, such as Bcl-2 homologous antagonist/killer (Bak), Bcl-2-associated X protein (Bax) and Bcl-2-interacting mediator of cell death (Bim). WEV+NP also altered the membrane potential of mitochondria in the PCa cells. Our data reveal the potential of nanoparticle-sustained delivery of snake venom as effective treatments for prostate cancer.
KeywordsApoptosis Bcl-2 Nanoparticles Proliferation Prostate Snake venom
B cell Lymphoma-2
Walterinnesia aegyptia venom
Walterinnesia aegyptia venom combined with nanoparticles
This work was supported by the National Plan for Science and Technology (NPST) funded by the King Abdulaziz City for Science and Technology (KACST) through project number 10-BIO969-02. The authors acknowledge Dr. Ahmed El-Toni at the King Abdullah Institute for Nanotechnology, King Saud University, for loading venom onto the silica nanoparticles. The authors also acknowledge Dr. Doaa Maximous at Surgical oncology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt, for kindly provided the prostate cancer samples.
Conflict of interest
The authors declare that they have no conflicts of interest.
The authors state that the manuscript has not been published or submitted elsewhere, state that the work complies with the ethical policies of the journal and state that the work has been conducted under internationally accepted ethical standards after relevant ethical review.
- 9.Qian Wu, Dhir Rajiv, Wells Alan (2012) Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion. Mol Cancer 11:3Google Scholar
- 11.Ha HK, Lee W, Park HJ, Lee SD, Lee JZ, Chung MK (2011) Clinical significance of CXCL16/CXCR6 expression in patients with prostate cancer. Mol Med Rep 4(3):419–424Google Scholar
- 18.Son DJ, Park MH, Chae SJ, Moon SO, Lee JW, Song HS, Moon DC, Kang SS, Kwon YE, Hong JT (2007) Inhibitory effect of snake venom toxin from Vipera lebetina turanica on hormone-refractory human prostate cancer cell growth: induction of apoptosis through inactivation of nuclear factor kappaB. Mol Cancer Ther 6(2):675–683PubMedCrossRefGoogle Scholar
- 20.Al-Sadoon MK, Abdel-Maksoud MA, Rabah DM, Badr G (2012) 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. Cell Physiol Biochem 30(3):653–665PubMedCrossRefGoogle Scholar
- 22.Song JK, Jo MR, Park MH, Song HS, An BJ, Song MJ, Han SB, Hong JT (2012) Cell growth inhibition and induction of apoptosis by snake venom toxin in ovarian cancer cell via inactivation of nuclear factor κB and signal transducer and activator of transcription 3. Arch Pharm Res 35(5):867–876PubMedCrossRefGoogle Scholar
- 34.Tsapakidis K, Vlachostergios PJ, Voutsadakis IA, Befani CD, Patrikidou A, Hatzidaki E, Daliani DD, Moutzouris G, Liakos P, Papandreou CN (2012) Bortezomib reverses the proliferative and antiapoptotic effect of neuropeptides on prostate cancer cells. Int J Urol 19(6):565–574PubMedCrossRefGoogle Scholar
- 41.Moorthi C, Manavalan R, Kathiresan K (2011) Nanotherapeutics to overcome conventional cancer chemotherapy limitations. J Pharm Pharm Sci 14(1):67–77Google Scholar
- 42.Kolluru LP, Rizvi SA, D’Souza M, D’Souza MJ (2012) Formulation development of albumin based theragnostic nanoparticles as a potential delivery system for tumor targeting. J Drug Target. Oct 5Google Scholar