title: Antileukemic effects of piperlongumine and alpha lipoic acid combination on Jurkat, MEC1 and NB4 cells in vitro.
abstract: OBJECTIVE
  This research indicated to evaluate the effects of piperlongumine (PL), a biologically active alkaloid, and alpha lipoic acid (ALA), a naturally occurring cofactor existed in multienzyme complexes regulating metabolism on leukemia cells. Excessive production of reactive oxygen species (ROS) can lead to oxidative stress, a state that has been observed in several hematopoietic malignancies, including acute and chronic myeloid leukemias. The importance of the association between oxidative stress and malignancy is not currently clear; however, there is evidence that tumor.derived ROS may promote cell survival, migration and metastasis, proliferation and even drug.resistance depending on the origin of the cancer. Increased oxidative stress in leukemic cells may represent a potential therapeutic target, although there are differing opinions on whether therapeutic strategies should aim to antagonize or further promote oxidative stress in leukemic cells.
  
  
  METHODS
  The effects of PL alone (5, 15, 30 μM) and in combination (30 μ M) with ALA (200 μ M) on Jurkat, NB4 and MEC1 leukemia cell lines were investigated through MTT, caspase-3 and cyclooxygenase-2 (COX-2) activities.
  
  
  RESULTS
  Inhibition of COX-2 and the induction of caspase.3 cleavage in Nb4 (acute promyelocytic leukemia) cells were found to be significant following PL application and synergistic effects with combination of ALA (inhibition of COX-2 as 23.74% and 3.55-fold increase of caspase-3).
  
  
  CONCLUSIONS
  PL and ALA may have a potential value as a therapeutic agent for patients with acute promyelocytic leukemia.
authors.affiliation: Department of Medical Biochemistry, Duzce University, Faculty of Medicine, Duzce, Turkey.
authors.forename: Merve
authors.initials: M
authors.lastname: Alpay
authors.affiliation: Department of Pharmacology and Toxicology, Ankara University, Faculty of Veterinary Medicine, Ankara, Turkey.
authors.forename: Begum
authors.initials: B
authors.lastname: Yurdakok-Dikmen
authors.affiliation: Department of Biochemistry, Ankara University, Faculty of Veterinary Medicine, Ankara, Turkey.
authors.forename: Gorkem
authors.initials: G
authors.lastname: Kismali
authors.affiliation: Department of Biochemistry, Ankara University, Faculty of Veterinary Medicine, Ankara, Turkey.
authors.forename: Tevhide
authors.initials: T
authors.lastname: Sel
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004148:Dioxolanes / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*; D010881:Piperidones
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3; D051546:Cyclooxygenase 2; D004148:Dioxolanes; D008063:Thioctic Acid; C498077:piperlongumine; D010881:Piperidones