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Synthetic retinoid CD437 induces apoptosis and acts synergistically with TRAIL receptor-2 agonist in malignant melanoma.

Abstract：

:The novel synthetic retinoid, CD437, shows potent anti-tumor activity in a range of different cancer cell lines and now serves as a prototype for development of new retinoid related molecules (RRMs). The purpose of this study was to examine the effect and cellular targets of CD437 in the human metastatic melanoma cell lines FEMX-1 and WM239. We showed that treatment with CD437 led to cell cycle arrest and induced apoptosis through both the extrinsic- and intrinsic pathways (caspase 8, -9 and PARP cleavage) in both cell lines. Interestingly, apoptosis was induced independently of DNA-fragmentation in FEMX-1 cells, and appeared partially caspase-independent in the WM239 cells. Additionally, up-regulation of CHOP mRNA and cathepsin D protein expression, following retinoid treatment, suggests involvement of the endoplasmatic reticulum (ER) and lysosomes, respectively. Combination of suboptimal concentrations of CD437 and lexatumumab, a TRAIL death receptor-2 agonist, resulted in synergistic reduction of viable cells, along with increased PARP cleavage. These results indicate that CD437 has a strong anti-neoplastic effect alone and in combination with lexatumumab in melanoma cell lines.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Magnussen GI,Ree Rosnes AK,Shahzidi S,Dong HP,Emilsen E,Engesæter B,Flørenes VA

doi

10.1016/j.bbrc.2012.03.023

subject

Has Abstract

pub_date

2012-04-13 00:00:00

pages

516-22

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(12)00470-6

journal_volume

420

pub_type

杂志文章

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