Apoptosis Induced by the Curcumin Analogue EF-24 Is Neither Mediated by Oxidative Stress-Related Mechanisms nor Affected by Expression of Main Drug Transporters ABCB1 and ABCG2 in Human Leukemia Cells

International Journal of Molecular Sciences
Nikola SkoupaPetr Mlejnek

Abstract

The synthetic curcumin analogue, 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone (EF-24), suppresses NF-κB activity and exhibits antiproliferative effects against a variety of cancer cells in vitro. Recently, it was reported that EF-24-induced apoptosis was mediated by a redox-dependent mechanism. Here, we studied the effects of N-acetylcysteine (NAC) on EF-24-induced cell death. We also addressed the question of whether the main drug transporters, ABCB1 and ABCG2, affect the cytotoxic of EF-24. We observed that EF-24 induced cell death with apoptotic hallmarks in human leukemia K562 cells. Importantly, the loss of cell viability was preceded by production of reactive oxygen species (ROS), and by a decrease of reduced glutathione (GSH). However, neither ROS production nor the decrease in GSH predominantly contributed to the EF-24-induced cell death. We found that EF-24 formed an adduct with GSH, which is likely the mechanism contributing to the decrease of GSH. Although NAC abrogated ROS production, decreased GSH and prevented cell death, its protective effect was mainly due to a rapid conversion of intra- and extra-cellular EF-24 into the EF-24-NAC adduct without cytotoxic effects. Furthermore, we found that neither overexpr...Continue Reading

References

Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A T FojoI Pastan
Jan 18, 1989·Journal of the National Cancer Institute·L J GoldsteinG M Brodeur
Mar 1, 1983·Environmental Health Perspectives·B KettererD J Meyer
Feb 19, 2000·Journal of Cellular Biochemistry·P Mlejnek, P Kuglík
Oct 25, 2003·Oncogene·Suresh V AmbudkarMichael M Gottesman
Jun 24, 2004·Bioorganic & Medicinal Chemistry·Brian K AdamsMamoru Shoji
Oct 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ricky A SharmaWilliam P Steward
Feb 25, 2006·Cell Death and Differentiation·T BraunG Kroemer
Mar 8, 2006·Cancer Letters·Melinda C Myzak, Roderick H Dashwood
Jun 16, 2007·Advances in Experimental Medicine and Biology·Cara A MosleyJames P Snyder
Aug 9, 2007·The Journal of Biological Chemistry·Karuppaiyah SelvendiranPeriannan Kuppusamy
Mar 15, 2008·Cancer Research·Dharmalingam SubramaniamShrikant Anant
Apr 25, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Ivo FrydrychPetra Krumpochova
Aug 7, 2008·Cell Cycle·Shala L ThomasParaskevi Giannakakou
Aug 8, 2009·Cell Death and Differentiation·R Franco, J A Cidlowski
Oct 27, 2009·Bioorganic & Medicinal Chemistry Letters·Aiming SunJames P Snyder
Oct 30, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Petr KosztyuPetr Mlejnek
Jan 10, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yingjian LiangLianxin Liu
Nov 30, 2013·Nature Reviews. Drug Discovery·Chiara GorriniTak W Mak
Jul 8, 2014·Chemico-biological Interactions·Petr Mlejnek, Petr Dolezel
Jun 29, 2015·Free Radical Biology & Medicine·Takafumi Suzuki, Masayuki Yamamoto
Jun 18, 2017·Chemico-biological Interactions·Petr MlejnekEliska Ruzickova

❮ Previous
Next ❯

Citations

Dec 1, 2017·International Journal of Molecular Sciences·Geoffrey Brown, Ewa Marcinkowska
Nov 2, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jerry D MonroeMichael E Smith
Jan 9, 2019·Frontiers in Oncology·Yonghan HeQingpeng Kong
Jul 25, 2019·European Journal of Medicinal Chemistry·Shijie ZhaoYumeng Wei
Nov 5, 2020·Journal of Medicinal Chemistry·Martina Bazzaro, Stig Linder
May 8, 2019·Journal of Agricultural and Food Chemistry·Chenyan HuaDanfeng Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection

Software Mentioned

SigmaPlot

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.