Alkylphosphocholines and curcumin induce programmed cell death in cutaneous T-cell lymphoma cell lines.
While most patients with early-stage cutaneous T-cell lymphomas (CTCL) have a very good prognosis, the survival of patients with extensive tumour stage and visceral involvement remains extremely poor and necessitates the development of more effective treatment modalities. In this study, we evaluated the in vitro effects of two alkylphosphocholines (APCs, miltefosine and erufosine) and the polyphenolic compound curcumin on 5 human CTCL cell lines (Hut-78, HH, MJ, My-La CD4+ and My-La CD8+). All tested drugs showed considerable cytotoxic activity, as determined by the MTT dye reduction assay. The IC50 values of both APCs ranged from the low micromolar level (Hut-78 cells) to 60-80μM (HH cells). The IC50 values of curcumin ranged from 12 to 24μM. All tested drugs induced apoptosis, as ascertained by morphological changes, DNA fragmentation and activation of caspase cascades. Miltefosine and erufosine induced dephosphorylation of Akt in My-La CD8+ cells and phosphorylation of JNK in Hut-78 and My-La CD8+ cells. APCs increased the level of the autophagic marker LC3B in Hut-78 and MJ cells. Results from co-treatment with autophagy modulators suggested that the cytotoxicity of APCs in CTCL cells is mediated, at least in part, by induction of autophagy.
Laboratory for Experimental Chemotherapy, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria; Center of Excellence - Translational Research in Haematology, National Specialised Hospital for Active Treatment of Haematological Diseases, Sofia, Bulgaria. Electronic address: deyanyosifov@abv.bg.
Deyan Y
DY
Yosifov
Laboratory for Experimental Chemotherapy, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria.
Kaloyan A
KA
Kaloyanov
Center of Excellence - Translational Research in Haematology, National Specialised Hospital for Active Treatment of Haematological Diseases, Sofia, Bulgaria; Laboratory of Haematopathology and Immunology, National Specialised Hospital for Active Treatment of Haematological Diseases, Sofia, Bulgaria.
Margarita L
ML
Guenova
Department of Dermatology and Venereology, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
Kamelia
K
Prisadashka
Department of Dermatology and Venereology, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
Maria B
MB
Balabanova
Toxicology and Chemotherapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Martin R
MR
Berger
Laboratory for Experimental Chemotherapy, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria; Center of Excellence - Translational Research in Haematology, National Specialised Hospital for Active Treatment of Haematological Diseases, Sofia, Bulgaria.
Spiro M
SM
Konstantinov
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010755:Organophosphates / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D010755:Organophosphates; D000644:Quaternary Ammonium Compounds; C472787:erucylphospho-N,N,N-trimethylpropylammonium; D010767:Phosphorylcholine; C039128:miltefosine; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases; D003474:Curcumin
Alkylphosphocholines; Apoptosis; Autophagy; Curcumin; Cutaneous T-cell lymphoma; Cytotoxicity; Erufosine; Miltefosine