Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines

Bredholt, Therese; Dimba, Elizabeth; Hagland, Hanne R.; Wergeland, Line; Skavland, Jørn; Fossan, Kjell Ove; Tronstad, Karl Johan; Johannessen, Anne Christine; Vintermyr, Olav Karsten; Gjertsen, Bjørn Tore

doi:10.1186/1476-4598-8-101

Cited by 47 publications

(66 citation statements)

References 48 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…-3 and -8 (Dimba et al, 2004;Bredholt et al, 2009). We also found khat-induced apoptosis after long-term treatment (16-24 h) in a concentration-dependent manner that appears to be followed by secondary necrosis.…”

Section: Figmentioning

confidence: 61%

Khat (Catha edulis) alters the phenotype and anti-microbial activity of peripheral blood mononuclear cells

Murdoch

Aziz

Fang

et al. 2011

Journal of Ethnopharmacology

View full text Add to dashboard Cite

Section: Figmentioning

confidence: 61%

Khat (Catha edulis) alters the phenotype and anti-microbial activity of peripheral blood mononuclear cells

Murdoch

Aziz

Fang

et al. 2011

Journal of Ethnopharmacology

View full text Add to dashboard Cite

“…HEK293 cell lines were cultivated in DMEM supplied with GlutaMAX™ (Invitrogen), 10% fetal calf serum (FCS; Gibco), and 50 IU penicillin/50 μg streptomycin ml −1 . The human leukemia cell lines NB4, HL-60, Molm-13, and MV4-11 were obtained and cultivated as previously described (Bredholt et al 2009). Ba/F3 suspension cells (DSMZ) were cultivated as for the human leukemia cells, but the medium contained in addition 10 % vol interleukin-containing conditioned medium derived from the WEHI-3B cell line (DSMZ).…”

Section: Cell Lines and Cultivationmentioning

confidence: 99%

Ectopic expression of Flt3 kinase inhibits proliferation and promotes cell death in different human cancer cell lines

et al. 2012

Self Cite

View full text Add to dashboard Cite

Stable ectopic expression of Flt3 receptor tyrosine kinase is usually performed in interleukin 3 (IL-3)-dependent murine cell lines like Ba/F3, resulting in loss of IL-3 dependence. Such high-level Flt3 expression has to date not been reported in human acute myeloid leukemia (AML) cell lines, despite the fact that oncogenic Flt3 aberrancies are frequent in AML patients. We show here that ectopic Flt3 expression in different human cancer cell lines might reduce proliferation and induce apoptotic cell death, involving Bax/Bcl2 modulation. Selective depletion of Flt3-expressing cells occurred in human AML cell lines transduced with retroviral Flt3 constructs, shown here using the HL-60 leukemic cell line. Flt3 expression was investigated in two cellular model systems, the SAOS-2 osteosarcoma cell line and the human embryonic kidney HEK293 cell line, and proliferation was reduced in both systems. HEK293 cells underwent apoptosis upon ectopic Flt3 expression and cell death could be rescued by overexpression of Bcl-2. Furthermore, we observed that the Flt3-induced inhibition of proliferation in HL-60 cells appeared to be Bax-dependent. Our results thus suggest that excessive Flt3 expression has growth-suppressive properties in several human cancer cell lines.

show abstract

“…16 Cell viability and proliferation assays Evaluation of apoptosis and inhibition of proliferation in cell lines and primary AML cells after drug treatment was performed using different assays; Hoechst 33342, Annexin-PI, 3 H-thymidine incorporation, ATP and Alamarblue assay, for details see Supplementary Information.…”

Section: Transmission Electron Microscopy (Tem)mentioning

confidence: 99%

Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia

et al. 2011

View full text Add to dashboard Cite

Although TP53 mutations are rare in acute myeloid leukemia (AML), wild type p53 function is habitually annulled through overexpression of MDM2 or through various mechanisms including epigenetic silencing by histone deacetylases (HDACs). We hypothesized that co-inhibition of MDM2 and HDACs, with nutlin-3 and valproic acid (VPA) would additively inhibit growth in leukemic cells expressing wild type TP53 and induce p53-mediated apoptosis. In vitro studies with the combination demonstrated synergistic induction of apoptosis in AML cell lines and patient cells. Nutlin-3 and VPA co-treatment resulted in massive induction of p53, acetylated p53 and p53 target genes in comparison with either agent alone, followed by p53 dependent cell death with autophagic features. In primary AML cells, inhibition of proliferation by the combination therapy correlated with the CD34 expression level of AML blasts. To evaluate the combination in vivo, we developed an orthotopic, NOD/SCID IL2rg null xenograft model of MOLM-13 (AML FAB M5a; wild type TP53) expressing firefly luciferase. Survival analysis and bioluminescent imaging demonstrated the superior in vivo efficacy of the dual inhibition of MDM2 and HDAC in comparison with controls. Our results suggest the concomitant targeting of MDM2-p53 and HDAC inhibition, may be an effective therapeutic strategy for the treatment of AML.

show abstract

Camptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell lines

Cited by 47 publications

References 48 publications

Khat (Catha edulis) alters the phenotype and anti-microbial activity of peripheral blood mononuclear cells

Khat (Catha edulis) alters the phenotype and anti-microbial activity of peripheral blood mononuclear cells

Ectopic expression of Flt3 kinase inhibits proliferation and promotes cell death in different human cancer cell lines

Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia

Contact Info

Product

Resources

About