TITLE

Cross-talk between calpain and caspase-3/-7 in cisplatin-induced apoptosis of melanoma cells: a major role of calpain inhibition in cell death protection and p53 status

AUTHOR(S)
Del Bello, B.; Moretti, D.; Gamberucci, A.; Maellaro, E.
PUB. DATE
April 2007
SOURCE
Oncogene;4/26/2007, Vol. 26 Issue 19, p2717
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The contribution of different proteolytic systems, in particular calpains and effector caspases, in apoptotic cell death is still controversial. In this paper, we show that during cisplatin-induced apoptosis of human metastatic melanoma cells, calpain activation, as measured in intact cells by two different fluorescent substrates, is an early event, taking place well before caspase-3/-7 activation, and progressively increasing during 48 h of treatment. Such activation appears to be independent from any intracellular calcium imbalance; in fact, an increase of cytosolic calcium along with emptying of the reticular stores occur only at very late stages, uniquely in frankly apoptotic, detached cells. Calpain activation proves to be an early and crucial event in the apoptotic machinery, as demonstrated by the significant protection of cell death in samples co-treated with the calpain inhibitors, MDL 28170, calpeptin and PD 150606, where a variable but significant reduction of both caspase-3/-7 activity and cell detachment is observed. Consistently, such a protective effect can be at least partially due to the impairment of cisplatin-induced p53 activation, occurring early in committed, preapoptotic cells. Furthermore, in late apoptotic cells, calpain activity is also responsible for the formation of a novel p53 proteolytic fragment (≈26 kDa), whose function is so far to be elucidated.Oncogene (2007) 26, 2717–2726. doi:10.1038/sj.onc.1210079; published online 27 November 2006
ACCESSION #
24943675

 

Related Articles

  • ROLA KALPAIN W APOPTOZIE. Marczak, Agnieszka // Problemy Terapii Monitorowanej;mar2008, Vol. 19 Issue 1, p59 

    Calpains and caspase are families of cysteine proteases that have important in the initiation, regulation and execution of cell death. This article shows recent reports on the function of calpains in apoptosis.

  • Ex vivo measurement of calpain activation in human peripheral blood lymphocytes by detection of immunoreactive products of calpastatin degradation. Mikosik, Anna; Zaremba, Anna; Puchalska, Zofia; Daca, Agnieszka; Smoleńska, Żaneta; Łopatniuk, Paulina; Mital, Andrzej; Hellmann, Andrzej; Bryl, Ewa; Witkowski, Jacek M. // Folia Histochemica et Cytobiologica;2007, Vol. 45 Issue 4, p343 

    Limited proteolysis of multiple intracellular proteins by endogenous Ca-dependent cysteine proteases - calpains - is an important regulatory mechanism for cell proliferation, apoptosis etc. Its importance for cellular functions is stressed by existence of endogenous calpain inhibitors -...

  • Calpain Inhibition: A Therapeutic Strategy Targeting Multiple Disease States. Carragher, N. O. // Current Pharmaceutical Design;Feb2006, Vol. 12 Issue 5, p615 

    The calpains represent a well-conserved family of calcium-dependent cysteine proteases. They consist of several ubiquitous and tissue specific isoforms and exhibit broad substrate specificity influencing many aspects of cell physiology including migration, proliferation and apoptosis. Calpain...

  • Serine proteases and calpains fulfill important supporting roles in the apoptotic tragedy of the cellular opera. Vandenabeele, P.; Orrenius, S.; Zhivotovsky, B. // Cell Death & Differentiation;Sep2005, Vol. 12 Issue 9, p1219 

    Explores the involvement of granzymes, lysosomal cathepsins, calpains, proteasomes and serine proteases in the regulation of apoptosis in terms of defined molecular pathways. Inclusion of numerous proteases localized in different intracellular compartments in cellular proteolytic machinery;...

  • HIV protease inhibitor therapy reverses neutrophil apoptosis in AIDS patients by direct calpain inhibition. Lichtner, M.; Mengoni, F.; Mastroianni, C. M.; Sauzullo, I.; Rossi, R.; De Nicola, M.; Vullo, V.; Ghibelli, L. // Apoptosis;Sep2006, Vol. 11 Issue 5, p781 

    The reduction of neutrophils apoptosis is one of the main non-virological effects of protease inhibitor (PI) therapy. We explore here whether this may be due to the cross-inhibition of calpain, an important non-virological target of PI in vitro. We found that the high basal level of neutrophils...

  • Theaflavins target Fas/caspase-8 and Akt/pBad pathways to induce apoptosis in p53-mutated human breast cancer cells. Lahiry, Lakshmishri; Saha, Baisakhi; Chakraborty, Juni; Adhikary, Arghya; Mohanty, Suchismita; Hossain, Dewan Md Sakib; Banerjee, Shuvomoy; Das, Kaushik; Sa, Gaurisankar; Das, Tanya // Carcinogenesis;Feb2010, Vol. 31 Issue 2, p259 

    The most common alterations found in breast cancer are inactivation or mutation of tumor suppressor gene p53. The present study revealed that theaflavins induced p53-mutated human breast cancer cell apoptosis. Pharmacological inhibition of caspase-8 or expression of dominant-negative...

  • Mimulone-Induced Autophagy through p53-Mediated AMPK/mTOR Pathway Increases Caspase-Mediated Apoptotic Cell Death in A549 Human Lung Cancer Cells. An, Hyun-Kyu; Kim, Kyoung-Sook; Lee, Ji-Won; Park, Mi-Hyun; Moon, Hyung-In; Park, Shin-Ji; Baik, Ji-Sue; Kim, Cheorl-Ho; Lee, Young-Choon // PLoS ONE;Dec2014, Vol. 9 Issue 12, p1 

    Anticancer properties and mechanisms of mimulone (MML), C-geranylflavonoid isolated from the Paulownia tomentosa fruits, were firstly elucidated in this study. MML prevented cell proliferation in a dose- and time-dependent way and triggered apoptosis through the extrinsic pathway in A549 human...

  • Structural biology: Enzyme knocked for a loop. Mellgren, Ronald L. // Nature;11/20/2008, Vol. 456 Issue 7220, p337 

    The article discusses how protein-digesting enzymes called proteinases can be stopped from attacking targets without destroying themselves. Proteinases breakdown other proteins and strategies have evolved to ensure they act appropriately. Topics include a discussion of the two crystallographic...

  • Cisplatin Plus Sodium Arsenite and Hyperthermia Induces Pseudo-G1 Associated Apoptotic Cell Death in Ovarian Cancer Cells. Muenyi, Clarisse S.; Trivedi, Abhaya P.; Helm, C. William; States, J. Christopher // Toxicological Sciences;May2014, Vol. 139 Issue 1, p74 

    Cisplatin is effective against solid tumors including ovarian cancer. However, inherent or acquired cisplatin resistance limits clinical success. We recently demonstrated that a combination of sodium arsenite (NaAsO2) and hyperthermia sensitizes p53-expressing ovarian cancer cells to cisplatin...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics