Cisplatin-mediated c-myc overexpression and cytochrome c (cyt c) release result in the up-regulation of the death receptors DR4 and DR5 and the activation of caspase 3 and caspase 9, likely responsible for the TRAIL-sensitizing effect of cisplatin

Medical Oncology
Xingchao ZhuQin Li

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reverses multidrug resistance (MDR) and induces apoptosis in MDR gastric carcinoma cells. In our previous study, cisplatin proved to be a sensitizing agent for TRAIL. To study the synergistic effects of cisplatin and TRAIL, we investigated the mechanism by which TRAIL reverses multidrug resistance, the role of c-myc in modulating the death receptors DR4 and DR5 and the relationship between cisplatin and cytochrome c (cyt c) release in SGC7901/VCR and SGC7901/DDP cells. We found that after treatment with TRAIL, the DNA-PKcs/Akt/GSK-3β pathway, which is positively correlated with the levels of MDR1 and MRP1, was significantly inhibited and that this tendency can be abolished by Z-DEVD-FMK (a specific caspase 3 inhibitor). We also found that suppression of c-myc by siRNA reduced the expression of DR4 and DR5 and that transfection with a pAVV-c-myc expression vector increased the expression of DR4 and DR5. Moreover, cisplatin increased the expression of c-myc in the presence of TRAIL, and there is a clear increase in cyt c release from mitochondria with the increasing concentrations of cisplatin. Meanwhile, the intrinsic death receptor pathway of caspase 9, as well as ...Continue Reading

References

Mar 21, 1998·British Journal of Haematology·J M NørgaardP Hokland
Jul 15, 1999·Biochemical and Biophysical Research Communications·M MandalR Kumar
Jul 13, 2001·Advances in Cancer Research·Y Shen, E White
Jun 24, 2003·The American Journal of Pathology·Etienne BlancGilda Raguénez
Dec 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adam J L CookChristopher J Jolly
Jan 28, 2006·World Journal of Gastroenterology : WJG·Ling Yang
May 6, 2010·JAMA : the Journal of the American Medical Association·William F AndersonCharles S Rabkin
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
May 3, 2013·International Journal of Oncology·Kriengsak LirdprapamongkolIkuo Saiki
Feb 1, 2014·International Journal of Oncology·Tomonori NakazatoMasahiro Kizaki
Feb 25, 2014·Apoptosis : an International Journal on Programmed Cell Death·Jian-Guo SunFei-Yan Liu

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Citations

Aug 8, 2015·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Shimin XuShuzhong Li
Sep 24, 2014·Neoplasia : an International Journal for Oncology Research·Roberta VenèFrancesca Tosetti
Apr 22, 2017·Clinical and Experimental Pharmacology & Physiology·Jianhua LiJingning Long
Jul 20, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Amina MedhatMustafa Mahmoud
Oct 25, 2017·Cancer Biomarkers : Section a of Disease Markers·Qi-Cai LiJiang Wu
Mar 24, 2016·World Journal of Gastroenterology : WJG·Gui-Mei KongFeng Qian
Jul 1, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Angela NebbiosoLucia Altucci
Jun 3, 2021·Membranes·Deborah M BoesDuncan G G McMillan
Dec 23, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Gaoxin LeiShuhua Tan

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