title: Curcumin potentiates antitumor activity of L-asparaginase via inhibition of the AKT signaling pathway in acute lymphoblastic leukemia.
abstract: L-asparaginase (L-ASP) is a universal component of therapy for acute lymphoblastic leukemia (ALL). Curcumin is a naturally occurring yellow pigment that is derived from the rhizome of Curcuma longa. In this study, we evaluated the cytotoxicity of the combined treatment of L-ASP and curcumin in three ALL cell lines. Synergistic cytotoxicity was observed in all three cell lines following the combined treatment of curcumin and L-ASP. Our results revealed that curcumin significantly enhanced the antitumor effect of L-ASP in the three ALL cell lines compared to that for L-ASP alone ( p < 0.05). Curcumin and L-ASP co-treatments induced apoptosis, via activation and cleavage of caspase-8 and BID cleavage accompanied by release of cytochrome c and activation of caspase-9/3, compared to the group treated with only L-ASP and the control group. Furthermore, the combination of curcumin and L-ASP led to significant reductions in phosphorylated AKT and expression of AKT-regulated gene products (FoxO1, GSK3β, IKKα, NF-κB, XIAP) compared with the group treated with only L-ASP and the control group. Overall, our ﬁndings suggest that curcumin potentiates the antitumor effects of L-ASP in acute lymphoblastic leukemia by constitutively inhibiting AKT and AKT-regulated gene products.
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P R China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Qi-Rong
authors.initials: QR
authors.lastname: Geng
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001215:Asparaginase / Q000494:pharmacology*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D010766:Phosphorylation / Q000187:drug effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D001215:Asparaginase; D003474:Curcumin