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Apoptosis

, Volume 18, Issue 3, pp 300–314 | Cite as

Snake (Walterinnesia aegyptia) venom-loaded silica nanoparticles induce apoptosis and growth arrest in human prostate cancer cells

  • Gamal BadrEmail author
  • Mohamed K. Al-Sadoon
  • Danny M. Rabah
  • Douaa Sayed
Original Paper

Abstract

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.

Keywords

Apoptosis Bcl-2 Nanoparticles Proliferation Prostate Snake venom 

Abbreviation

Bcl-2

B cell Lymphoma-2

NP

Nanoparticles

PCa

Prostate cancer

WEV

Walterinnesia aegyptia venom

WEV+NP

Walterinnesia aegyptia venom combined with nanoparticles

Notes

Acknowledgments

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.

Ethical approval

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.

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Gamal Badr
    • 1
    • 2
    Email author
  • Mohamed K. Al-Sadoon
    • 3
  • Danny M. Rabah
    • 1
    • 4
  • Douaa Sayed
    • 5
  1. 1.Princess Johara Alibrahim Center for Cancer Research, Prostate Cancer Research ChairCollege of Medicine King Saud UniversityRiyadhSaudi Arabia
  2. 2.Zoology Department, Faculty of ScienceAssiut UniversityAssiutEgypt
  3. 3.Zoology Department, College of ScienceKing Saud UniversityRiyadhSaudi Arabia
  4. 4.Department of Urology/Surgery, College of MedicineKing Saud UniversityRiyadhSaudi Arabia
  5. 5.Clinical Pathology DepartmentSouth Egypt Cancer Institute, Assiut UniversityAssiutEgypt

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