The combination of ADI-PEG20 and TRAIL effectively increases cell death in melanoma cell lines.
Current treatment for advanced, metastatic melanoma is not very effective, and new modalities are needed. ADI-PEG20 is a drug that specifically targets ASS-negative malignant melanomas while sparing the ASS-expressing normal cells. Although laboratory research and clinical trials showed promising results, there are some ASS-negative cell lines and patients that can develop resistance to this drug. In this report, we combined ADI-PEG20 with another antitumor drug TRAIL to increase the killing of malignant melanoma cells. This combination can greatly inhibit cell growth (to over 80%) and also enhanced cell death (to over 60%) in four melanoma cell lines tested compared with control. We found that ADI-PEG20 could increase the cell surface receptors DR4/5 for TRAIL and that caspase activity correlated with the increased cell death. These two drugs could also increase the level of Noxa while decrease that of survivin. We propose that these two drugs can complement each other by activating the intrinsic and extrinsic apoptosis pathways, thus enhance the killing of melanoma cells.
Sylverster Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, Miami, FL 33136, USA.
Min
M
You
Niramol
N
Savaraj
Medhi
M
Wangpaichitr
Chunjing
C
Wu
M Tien
MT
Kuo
Javier
J
Varona-Santos
Dao M
DM
Nguyen
Lynn
L
Feun
D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D045744:Cell Line, Tumor; D006801:Humans; D006867:Hydrolases / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000627:therapeutic use*
C498702:PMAIP1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; D011092:Polyethylene Glycols; D006867:Hydrolases; C512527:ADI PEG20