Curcumin synergistically augments bcr/abl phosphorothioate antisense oligonucleotides to inhibit growth of chronic myelogenous leukemia cells
Abstract
Aim: To investigate the growth inhibition effect of the combination of bcr/abl
phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur),
and the possible mechanisms of cur on the chronic myelogenous leukemia cell line
K562. Methods: The K562 cell line was used as a P210bcr/abl-positive cell model in
vitro and was exposed to different concentrations of PS-ASODN (0–20 μmol/L),
cur (0–20 μmol/L), or a combination of both. Growth inhibition and apoptosis of
K562 cells were assessed by MTT assay and AO/EB fluorescent staining, respectively.
The expression levels of P210bcr/abl, NF-κB and heat shock protein 90 (Hsp90)
were assessed by Western blot. Results: Exposure to cur (5–20 μmol/L) and PSASODN
(5–20 μmol/L) resulted in a synergistic inhibitory effect on cell growth.
Growth inhibition was associated with the inhibition of the proliferation and induction
of apoptosis. Western blot analysis showed that the drugs synergistically
downregulated the level of P210bcr/abl and NF-κB. Cur downregulated Hsp90,
whereas no synergism was observed when cur was combined with PS-ASODN.
Conclusion: PS-ASODN and cur exhibited a synergistic inhibitory effect on the
cell growth of K562. The synergistic growth inhibition was mediated through
different mechanisms that involved the inhibition of P210bcr/abl.
Keywords:
phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur),
and the possible mechanisms of cur on the chronic myelogenous leukemia cell line
K562. Methods: The K562 cell line was used as a P210bcr/abl-positive cell model in
vitro and was exposed to different concentrations of PS-ASODN (0–20 μmol/L),
cur (0–20 μmol/L), or a combination of both. Growth inhibition and apoptosis of
K562 cells were assessed by MTT assay and AO/EB fluorescent staining, respectively.
The expression levels of P210bcr/abl, NF-κB and heat shock protein 90 (Hsp90)
were assessed by Western blot. Results: Exposure to cur (5–20 μmol/L) and PSASODN
(5–20 μmol/L) resulted in a synergistic inhibitory effect on cell growth.
Growth inhibition was associated with the inhibition of the proliferation and induction
of apoptosis. Western blot analysis showed that the drugs synergistically
downregulated the level of P210bcr/abl and NF-κB. Cur downregulated Hsp90,
whereas no synergism was observed when cur was combined with PS-ASODN.
Conclusion: PS-ASODN and cur exhibited a synergistic inhibitory effect on the
cell growth of K562. The synergistic growth inhibition was mediated through
different mechanisms that involved the inhibition of P210bcr/abl.