Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Aug;103(8):1538-45.
doi: 10.1111/j.1349-7006.2012.02335.x. Epub 2012 Jul 10.

Sphingosine kinase-1 Inhibition Sensitizes Curcumin-Induced Growth Inhibition and Apoptosis in Ovarian Cancer Cells

Affiliations
Free article

Sphingosine kinase-1 Inhibition Sensitizes Curcumin-Induced Growth Inhibition and Apoptosis in Ovarian Cancer Cells

Yan-li Yang et al. Cancer Sci. .
Free article

Abstract

Recent published studies suggest that increasing levels of ceramides enhance the chemo-sensitivity of curcumin. Using in vitro approaches, we analyzed the impact of sphingosine kinase-1 (SphK-1) inhibition on ceramide production, and evaluated SphK1 inhibitor II (SKI-II) as a potential curcumin chemo-sensitizer in ovarian cancer cells. We found that SphK1 is overexpressed in ovarian cancer patients' tumor tissues and in cultured ovarian cancer cell lines. Inhibition of SphK1 by SKI-II or by RNA interference (RNAi) knockdown dramatically enhanced curcumin-induced apoptosis and growth inhibition in ovarian cancer cells. SKI-II facilitated curcumin-induced ceramide production, p38 activation and Akt inhibition. Inhibition of p38 by the pharmacological inhibitor (SB 203580), a dominant-negative expression vector, or by RNAi diminished curcumin and SKI-II co-administration-induced ovarian cancer cell apoptosis. In addition, restoring Akt activation introducing a constitutively active Akt, or inhibiting ceramide production by fumonisin B1 also inhibited the curcumin plus SKI-II co-administration-induced in vitro anti-ovarian cancer effect, suggesting that ceramide accumulation, p38 activation and Akt inhibition are downstream effectors. Our findings suggest that low, well-tolerated doses of SKI-II may offer significant improvement to the clinical curcumin treatment of ovarian cancer.

Similar articles

See all similar articles

Cited by 14 articles

See all "Cited by" articles

Publication types

Feedback