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Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells.
Free Radic Biol Med. 2008 Nov 15; 45(10):1403-12.FR

Abstract

Evidence that curcumin may have anticancer activities has renewed interest in its potential to prevent and treat disease. In this study, we show that curcumin-mediated rapid generation of reactive oxygen species (ROS) leads to apoptosis by modulating different apoptotic pathways in mouse fibroblast L929 cells. We show for the first time that curcumin-induced rapid ROS generation causes the release of apoptosis inducing factor (AIF) from the mitochondria to the cytosol and nucleus, hence, leading to caspase 3-independent apoptosis. However, our studies also show that curcumin induces the release of cytochrome c from mitochondria, causing activation of caspase 3, and concomitant PARP cleavage, which is the hallmark of caspase-dependent apoptosis. Furthermore, curcumin-induced ROS generation leads to the induction of the proapoptotic protein p53 and its effector protein p21 and down-regulation of cell cycle regulatory proteins such as Rb and cyclin D1 and D3. Both glutathione (GSH) and N-acetylcysteine (NAC) pretreatment resulted in the complete inhibition of curcumin-induced ROS generation, AIF release from mitochondria, and caspase activation. Additionally, pretreatment of L929 cells with these antioxidants completely blocked the induction of p53-dependent p21 accumulation. In conclusion, our data show that in addition to caspase 3 activation, curcumin-induced rapid ROS generation leads to AIF release, and the activation of the caspase-independent apoptotic pathway.

Authors+Show Affiliations

Cell Signaling Laboratory, Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18762247

Citation

Thayyullathil, Faisal, et al. "Rapid Reactive Oxygen Species (ROS) Generation Induced By Curcumin Leads to Caspase-dependent and -independent Apoptosis in L929 Cells." Free Radical Biology & Medicine, vol. 45, no. 10, 2008, pp. 1403-12.
Thayyullathil F, Chathoth S, Hago A, et al. Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells. Free Radic Biol Med. 2008;45(10):1403-12.
Thayyullathil, F., Chathoth, S., Hago, A., Patel, M., & Galadari, S. (2008). Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells. Free Radical Biology & Medicine, 45(10), 1403-12. https://doi.org/10.1016/j.freeradbiomed.2008.08.014
Thayyullathil F, et al. Rapid Reactive Oxygen Species (ROS) Generation Induced By Curcumin Leads to Caspase-dependent and -independent Apoptosis in L929 Cells. Free Radic Biol Med. 2008 Nov 15;45(10):1403-12. PubMed PMID: 18762247.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells. AU - Thayyullathil,Faisal, AU - Chathoth,Shahanas, AU - Hago,Abdulkader, AU - Patel,Mahendra, AU - Galadari,Sehamuddin, Y1 - 2008/08/16/ PY - 2008/03/07/received PY - 2008/07/20/revised PY - 2008/08/05/accepted PY - 2008/9/3/pubmed PY - 2009/3/25/medline PY - 2008/9/3/entrez SP - 1403 EP - 12 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 45 IS - 10 N2 - Evidence that curcumin may have anticancer activities has renewed interest in its potential to prevent and treat disease. In this study, we show that curcumin-mediated rapid generation of reactive oxygen species (ROS) leads to apoptosis by modulating different apoptotic pathways in mouse fibroblast L929 cells. We show for the first time that curcumin-induced rapid ROS generation causes the release of apoptosis inducing factor (AIF) from the mitochondria to the cytosol and nucleus, hence, leading to caspase 3-independent apoptosis. However, our studies also show that curcumin induces the release of cytochrome c from mitochondria, causing activation of caspase 3, and concomitant PARP cleavage, which is the hallmark of caspase-dependent apoptosis. Furthermore, curcumin-induced ROS generation leads to the induction of the proapoptotic protein p53 and its effector protein p21 and down-regulation of cell cycle regulatory proteins such as Rb and cyclin D1 and D3. Both glutathione (GSH) and N-acetylcysteine (NAC) pretreatment resulted in the complete inhibition of curcumin-induced ROS generation, AIF release from mitochondria, and caspase activation. Additionally, pretreatment of L929 cells with these antioxidants completely blocked the induction of p53-dependent p21 accumulation. In conclusion, our data show that in addition to caspase 3 activation, curcumin-induced rapid ROS generation leads to AIF release, and the activation of the caspase-independent apoptotic pathway. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/18762247/Rapid_reactive_oxygen_species__ROS__generation_induced_by_curcumin_leads_to_caspase_dependent_and__independent_apoptosis_in_L929_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(08)00451-6 DB - PRIME DP - Unbound Medicine ER -