Possible Selective Cytotoxicity of Vanadium Complex on Breast Cancer Cells Involving Pathophysiological Pathways

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.

Molecular and Cellular Mechanisms of Cytotoxic Activity of Vanadium Compounds against Cancer Cells

“…In another study, we have found that an oxidovanadium complex with quinolinium cation (66) induced autophagic process in pancreatic cancer cells with simultaneous increase in the RAGE protein level [79]. Autophagy was also detected in vanadium-treated (90) breast cancer cells [101]. An interesting study has been performed in hypoxic conditions.…”

“…Oral squamous cell carcinoma Cal27 Induction of apoptosis: poly(ADPribose)polymerase cleavage Autophagy was also detected in vanadium-treated (90) breast cancer cells [101]. An interesting study has been performed in hypoxic conditions.…”

Fortification of biscuit with sidr leaf and flaxseed mitigates immunosuppression and nephrotoxicity induced by cyclosporine A

“…Nevertheless, cytokines could conversely promote or inhibit the progression of autophagy (Jiang et al., 2019). Moreover, TGF‐β is a common regulator that mediates the cross talk between autophagic and apoptotic cell death (El‐Shafey & Elsherbiny, 2019a, El‐Shafey and Elsherbiny, 2019b; Wu et al., 2016). Thus, reduction of its level can suppress CsA‐induced renal apoptosis and promote renal‐protective activities of sidr and flaxseeds.…”

“…Cell suspension (100 µl) was taken in another 5 ml test tube, then, 5 µl of annexin V (FITC label) and 5 µl PI (PE label) were added directly. The mixture was incubated for at least 15 min in the dark at 37°C then cells were re‐dissolved in 200 µl 1× binding buffer and analyzed (El‐Shafey & Elsherbiny, 2019a).…”

Exploring the Potential of Metallodrugs as Chemotherapeutics for Triple Negative Breast Cancer

“…Compounds containing the transition metal vanadium enhance redox reactions and interactions with nucleic acids, which promote mechanisms of cell death such as cell cycle arrest and DNA damage in various cancer types. [172,173] Recent studies in MDA-MB-231 cells have shown apoptotic and autophagic cell death with notch pathway inhibition of a vanadium-based complex, compound 58, a oxidovanadium (IV) complex by Gonzalez-Baró and co-workers with a chelating ligand made from the condensation reaction of o-vanillin and 2thiophenemethylamine. [174] Cellular studies in MDA-MB-231 cells showed cytotoxicity (IC 50 = 29 � 1.7 μM, 48 h), an apoptotic cell death, antimigratory activity, and increased ROS production.…”