PMID:24225136

Citation	Yosifov, DY, Kaloyanov, KA, Guenova, ML, Prisadashka, K, Balabanova, MB, Berger, MR and Konstantinov, SM (2014) Alkylphosphocholines and curcumin induce programmed cell death in cutaneous T-cell lymphoma cell lines. Leuk. Res. 38:49-56
Abstract	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.
Links	PubMed Online version:10.1016/j.leukres.2013.10.011
Keywords	Antineoplastic Agents/pharmacology; Apoptosis/drug effects; Autophagy/drug effects; Blotting, Western; Caspases/metabolism; Cell Line, Tumor; Cell Survival/drug effects; Curcumin/pharmacology; Dose-Response Relationship, Drug; Humans; Inhibitory Concentration 50; JNK Mitogen-Activated Protein Kinases/metabolism; Lymphoma, T-Cell, Cutaneous/metabolism; Lymphoma, T-Cell, Cutaneous/pathology; Microtubule-Associated Proteins/metabolism; Organophosphates/pharmacology; Phosphorylation/drug effects; Phosphorylcholine/analogs & derivatives; Phosphorylcholine/pharmacology; Poly(ADP-ribose) Polymerases/metabolism; Proto-Oncogene Proteins c-akt; Quaternary Ammonium Compounds/pharmacology; Skin Neoplasms/metabolism; Skin Neoplasms/pathology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PHOP1		GO:0044606: phosphocholine hydrolase activity	ECO:0000314:		F		Figure 1 shows some of the human phosphocholine hydrolase enzymes and the correlation between various cytotoxic t cell lines and apoptosis. Without the phosphocholine hydrolase activity of these enzymes, apoptosis wouldn't be induced and there would be no reduction in percent survival.	complete CACAO 10117

References

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