Menadione : Sodium Orthovanadate Combination Eliminates and Inhibits Migration of Detached Cancer Cells

Abstract

Exposure of cancer cells to anticancer agents in cultures induces detachment of cells that are usually considered dead. These drug-induced detached cells (D-IDCs) may represent a clinical problem for chemotherapy since they may survive anoikis, enter the circulation, invade other tissues and resume proliferation, creating a metastasis, especially in tissues where the bioavailability of anticancer agents is not enough to eliminate all cancer cells. In this study we evaluated the antiproliferative effect of menadione : sodium orthovanadate (M : SO) combination on A549 lung cancer cells as well as the ability of M : SO to induce cell detachment. In addition, we followed the fate and chemosensitivity of M : SO-induced detached cells. Using transwell chambers, we found that a fraction of the M : SO-induced detached cells were viable and, furthermore, were able to migrate, re-attach, and resume proliferation when re-incubated in drug-free media. The total elimination of A549 detachment-resistant cells and M : SO-induced detached cells were successfully eliminated by equivalent M : SO concentration (17.5 μM : 17.5 μM). Thus, M : SO prevented cell migration. Similar results were obtained on DBTRG.05MG human glioma cells. Our data guarantee further studies to evaluate the in vivo occurrence of D-IDCs, their implications for invasiveness and metastasis and their sensitivity to anticancer drugs.

Menadione (Vitamin K3) Induces Apoptosis of Human Oral Cancer Cells and Reduces their Metastatic Potential by Modulating the Expression of Epithelial to Mesenchymal Transition Markers and Inhibiting Migration

“…A combination of menadione and ascorbate resulted in oxidative stress-mediated cell death in liver cancer cells (Veerax et al, 2004). A combination of menadione and sodium orthovanadate eliminated and inhibited migration of detached cancer cells (Delwar et al, 2012). Combination of menadione with ethacrynic acid inhibited angiogenesis by down regulating vascular endothelial growth factor expression and blocking HIF-α interaction with p300 thereby inhibiting hypoxia in cancer cells (Na et al, 2013).…”

Nitropropenyl Benzodioxole, An Anti-Infective Agent with Action as a Protein Tyrosine Phosphatase Inhibitor

“…It has been investigated as a possible anti-tumor agent [52, 53]. Benzyl-β-nitroethene and derivatives have also been shown to be inhibitors of protein tyrosine phosphatases PTP1B and Yop [10, 12].…”

“…Sodium orthovanadate is a broad and highly active phosphatase inhibitor, as would be expected of a phosphate analog, and widely used as a PTP positive inhibitor control in enzyme assays. It has been investigated as a possible anti-tumor agent [ 52 , 53 ]. Benzyl-β-nitroethene and derivatives have also been shown to be inhibitors of protein tyrosine phosphatases PTP1B and Yop [ 10 , 12 ].…”

Novel drug candidates for treating esophageal carcinoma: A study on differentially expressed genes, using connectivity mapping and molecular docking

“…Compared with clofazimine, it appears that menadione, which is also known as vitamin K3, has attracted more attention from the perspective of cancer treatment. Menadione has been identified to exhibit significant therapeutic benefits in the treatment of gastric cancer ( 55 ), prostate cancer ( 56 ), oral cancer ( 57 ) and breast cancer ( 58 ). Furthermore, the latest research indicated that menadione may increase anticancer activity by combining ROS-generating agents ( 59 ), but how it works in ESCA treatment requires further investigation.…”