Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/49207
Title: The curcumin analog DM-1 induces apoptotic cell death in melanoma
Author: Faião Flores,F.
Quincoces Suárez, J.A.
Maria Engler, S.S.
Soto Cerrato, Vanessa
Pérez Tomás, Ricardo E.
Maria, D.A.
Keywords: Melanoma
Quimioteràpia
Apoptosi
Melanoma
Chemotherapy
Apoptosis
Issue Date: 29-Jan-2013
Publisher: Springer Verlag
Abstract: The main difficulty in the successful treatment of metastatic melanoma is that this type of cancer is known to be resistant to chemotherapy. Chemotherapy remains the treatment of choice, and dacarbazine (DTIC) is the best standard treatment. The DM-1 compound is a curcumin analog that possesses several curcumin characteristics, such as antiproliferative, antitumor, and antimetastatic properties. The objective of this study was to evaluate the signaling pathways involved in melanoma cell death after treatment with DM-1 compared to the standard agent for melanoma treatment, DTIC. Cell death was evaluated by flow cytometry for annexin V and iodide propide, cleaved caspase 8, and TNF-R1 expression. Hoechst 33342 staining was evaluated by fluorescent microscopy; lipid peroxidation and cell viability (MTT) were evaluated by colorimetric assays. The antiproliferative effects of the drugs were evaluated by flow cytometry for cyclin D1 and Ki67 expression. Mice bearing B16F10 melanoma were treated with DTIC, DM-1, or both therapies. DM-1 induced significant apoptosis as indicated by the presence of cleaved caspase 8 and an increase in TNF-R1 expression in melanoma cells. Furthermore, DM-1 had antiproliferative effects in this the same cell line. DTIC caused cell death primarily by necrosis, and a smaller melanoma cell population underwent apoptosis. DTIC induced oxidative stress and several physiological changes in normal melanocytes, whereas DM-1 did not significantly affect the normal cells. DM-1 antitumor therapy in vivo showed tumor burden decrease with DM-1 monotherapy or in combination with DTIC, besides survival rate increase. Altogether, these data confirm DM-1 as a chemotherapeutic agent with effective tumor control properties and a lower incidence of side effects in normal cells compared to DTIC.
Note: Versió postprint del document publicat a: http://dx.doi.org/10.1007/s13277-013-0653-y
It is part of: Tumor Biology, 2013, vol. 34, num. 2, p. 1119-29
Related resource: http://dx.doi.org/10.1007/s13277-013-0653-y
URI: http://hdl.handle.net/2445/49207
ISSN: 1010-4283
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

Files in This Item:
File Description SizeFormat 
621282.pdf1.22 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.