Next Article in Journal
Novel Combinations for the Treatment of Metastatic Breast Cancer
Next Article in Special Issue
Oxidative Stress and Exhaled Breath Analysis: A Promising Tool for Detection of Lung Cancer
Previous Article in Journal
Precancer: The Beginning and the End of Cancer. Edited by Jules J. Berman, MD, PhD (E-Mail: with G. William Moore, MD, PhD. Jones & Bartlett Publishers: Sudbury, MA, USA, 2009; 186 pp; 42.95$; ISBN: 9780763777845
Cancers 2009, 1(1), 23-38; doi:10.3390/cancers1010023

N′1,N′3-Dimethyl-N′1,N′3-bis(phenylcarbonothioyl) Propanedihydrazide (Elesclomol) Selectively Kills Cisplatin Resistant Lung Cancer Cells through Reactive Oxygen Species (ROS)

1 V.A. Medical Center, Hematology/Oncology, Miami, FL 33125, USA 2 Sylvester Cancer Center, School of Medicine, University of Miami, Miami, FL, 33136, USA
* Author to whom correspondence should be addressed.
Received: 11 November 2009 / Revised: 25 November 2009 / Accepted: 8 December 2009 / Published: 16 December 2009
(This article belongs to the Special Issue Oxidative Stress and Cancer)
View Full-Text   |   Download PDF [313 KB, uploaded 17 December 2009]   |   Browse Figures


Cisplatin is an important chemotherapeutic agent in lung cancer treatment. The mechanism of drug resistance to cisplatin is complex and historically has been difficult to overcome. We report here that cisplatin resistant lung cancer cell lines possess high basal levels of reactive oxygen species (ROS) when compared to normal cells and their parental cell counterparts. These resistant cells also have low thioredoxin (TRX) levels which may be one of the contributory factors to high ROS. N′1,N′3-dimethyl-N′1,N'3-bis(phenylcarbonothioyl) propanedihydrazide (elesclomol), an agent known to increase ROS is selectively toxic to cisplatin-resistant cells, while sparing normal cells and the parental counterpart. The cytotoxic effect of elesclomol in resistant cells is accompanied by further decreases in TRX and glutathione (GSH) antioxidant systems, while opposite results were found in parental cells. The ID50 of elesclomol in cisplatin-resistant cells ranged from 5–10 nM, which is well within clinically achievable ranges. N-Acetylcysteine (NAC), which is known to neutralize ROS, can abolish the cytotoxic effect of elesclomol, suggesting that the cytotoxic effect results from increased ROS. Overall, our data suggest that elesclomol selectively kills cisplatin-resistant tumor cells through increased ROS. This agent may hold potential to overcome cisplatin resistance and should be further explored to treat patients who have failed cisplatin therapy.
Keywords: lung cancer; drug resistant; cisplatin; ROS; elesclomol lung cancer; drug resistant; cisplatin; ROS; elesclomol
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
MDPI and ACS Style

Wangpaichitr, M.; Wu, C.; You, M.; Maher, J.C.; Dinh, V.; Feun, L.G.; Savaraj, N. N′1,N′3-Dimethyl-N′1,N′3-bis(phenylcarbonothioyl) Propanedihydrazide (Elesclomol) Selectively Kills Cisplatin Resistant Lung Cancer Cells through Reactive Oxygen Species (ROS). Cancers 2009, 1, 23-38.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert