Title:Possible Selective Cytotoxicity of Vanadium Complex on Breast Cancer Cells Involving Pathophysiological Pathways
Volume: 19
Issue: 17
Author(s): Eman S. El-Shafey*Eslam S. Elsherbiny
Affiliation:
- Department of Biochemistry, Faculty of Science, Damietta University, Damietta,Egypt
Keywords:
Apoptosis, autophagy, Notch1, vanadium complex, triple negative breast cancer, AVO.
Abstract:
Background: Triple-Negative Breast Cancers (TNBC) are among the most aggressive and therapyresistant
breast tumors. Development of new treatment strategies that target pathways involved in cancer cells
resistance is an attractive candidate to overcome therapeutic resistance.
Objective: To clarify the antitumor activity of [VO (bpy)2 Cl] Cl complex as a new therapeutic agent through
studying the interplay between apoptosis, autophagy and notch signaling pathways.
Methods: Proliferation of MDA-MB-231 cells and IC50 value of the vanadium complex were assessed by MTT
assay. Flow cytometry was utilized to detect cell cycle distribution, apoptosis assay, LC3 levels and Acid
Vascular Organelles (AVOs). Caspase 3 levels were detected by ELISA. Changes in Notch1 gene expression
were assessed by real-time PCR. AVOs qualitative detection was assessed by a fluorescence microscope.
Results: The growth of MDA-MB-231 cells was suppressed after treatment with [VO (bpy)2 Cl] Cl complex, in
a dose-dependent manner. The affinity for apoptotic cell death induction was shown through the increase in the
sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase 3 levels. The affinity
for autophagic cell death induction was observed through the increase in the G0/G1 phase, G2/M arrest, the
increase of AVOs red fluorescence and elevated LC3 levels. The affinity for notch pathway inhibition was
shown through the suppression of Notch 1 gene expression.
Conclusion: [VO (bpy)2 Cl] Cl complex could be a promising candidate as therapeutic agent targeting different
therapeutic targets including apoptosis, autophagy and notch signaling pathways.
