Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium-dependent activation of HIF-1alpha and P-glycoprotein overexpression.

ABSTRACT:

Background and purpose

Artemisinin is an antimalarial drug exerting pleiotropic effects, such as the inhibition of the transcription factor nuclear factor-kappa B and of the sarcoplasmic/endoplasmic reticulum Ca(++)-ATPase (SERCA) of P. falciparum. As the sesquiterpene lactone thapsigargin, a known inhibitor of mammalian SERCA, enhances the expression of P-glycoprotein (Pgp) by increasing the intracellular Ca(++) ([Ca(++)](i)) level, we investigated whether artemisinin and its structural homologue parthenolide could inhibit SERCA in human colon carcinoma HT29 cells and induce a resistance to doxorubicin.

Experimental approach

HT29 cells were incubated with artemisinin or parthenolide and assessed for SERCA activity, [Ca(++)](i) levels, Pgp expression, doxorubicin accumulatio

SUBMITTER: Riganti C 

PROVIDER: S-EPMC2697684 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature