Tags

Type your tag names separated by a space and hit enter

Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells.
Clin Cancer Res. 2005 Mar 15; 11(6):2379-88.CC

Abstract

PURPOSE

To test whether and how selenium enhances the apoptosis potency of selected chemotherapeutic drugs in prostate cancer (PCA) cells.

EXPERIMENTAL DESIGN

DU145 and PC3 human androgen-independent PCA cells were exposed to minimal apoptotic doses of selenium and/or the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38), the topoisomerase II inhibitor etoposide or the microtubule inhibitor paclitaxel/taxol. Apoptosis was measured by ELISA for histone-associated DNA fragments, by flow cytometric analysis of sub-G(1) fraction, and by immunoblot analysis of cleaved poly(ADP-ribose)polymerase. Pharmacologic inhibitors were used to manipulate caspases and c-Jun-NH(2)-terminal kinases (JNK).

RESULTS

The methylselenol precursor methylseleninic acid (MSeA) increased the apoptosis potency of SN38, etoposide, or paclitaxel by several folds higher than the expected sum of the apoptosis induced by MSeA and each drug alone. The combination treatment did not further enhance JNK1/2 phosphorylation that was induced by each drug in DU145 cells. The JNK inhibitor SP600125 substantially decreased the activation of caspases and apoptosis induced by MSeA combination with SN38 or etoposide and completely blocked these events induced by MSeA/paclitaxel. The caspase-8 inhibitor zIETDfmk completely abolished apoptosis and caspase-9 and caspase-3 cleavage, whereas the caspase-9 inhibitor zLEHDfmk significantly decreased caspase-3 cleavage and apoptosis but had no effect on caspase-8 cleavage. None of these caspase inhibitors abolished JNK1/2 phosphorylation. A JNK-independent suppression of survivin by SN38 and etoposide, but not by paclitaxel, was also observed. In contrast to MSeA, selenite did not show any enhancing effect on the apoptosis induced by these drugs.

CONCLUSIONS

MSeA enhanced apoptosis induced by cancer therapeutic drugs in androgen-independent PCA cells. In DU145 cells, the enhancing effect was primarily through interactions between MSeA and JNK-dependent targets to amplify the caspase-8-initiated activation cascades. The results suggest a novel use of methyl selenium for improving the chemotherapy of PCA.

Authors+Show Affiliations

Hormel Institute, University of Minnesota, 801 16th Avenue Northeast, Austin, MN 55912, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15788689

Citation

Hu, Hongbo, et al. "Methylseleninic Acid Potentiates Apoptosis Induced By Chemotherapeutic Drugs in Androgen-independent Prostate Cancer Cells." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 11, no. 6, 2005, pp. 2379-88.
Hu H, Jiang C, Ip C, et al. Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells. Clin Cancer Res. 2005;11(6):2379-88.
Hu, H., Jiang, C., Ip, C., Rustum, Y. M., & Lü, J. (2005). Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 11(6), 2379-88.
Hu H, et al. Methylseleninic Acid Potentiates Apoptosis Induced By Chemotherapeutic Drugs in Androgen-independent Prostate Cancer Cells. Clin Cancer Res. 2005 Mar 15;11(6):2379-88. PubMed PMID: 15788689.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells. AU - Hu,Hongbo, AU - Jiang,Cheng, AU - Ip,Clement, AU - Rustum,Youcef M, AU - Lü,Junxuan, PY - 2005/3/25/pubmed PY - 2005/7/1/medline PY - 2005/3/25/entrez SP - 2379 EP - 88 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 11 IS - 6 N2 - PURPOSE: To test whether and how selenium enhances the apoptosis potency of selected chemotherapeutic drugs in prostate cancer (PCA) cells. EXPERIMENTAL DESIGN: DU145 and PC3 human androgen-independent PCA cells were exposed to minimal apoptotic doses of selenium and/or the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38), the topoisomerase II inhibitor etoposide or the microtubule inhibitor paclitaxel/taxol. Apoptosis was measured by ELISA for histone-associated DNA fragments, by flow cytometric analysis of sub-G(1) fraction, and by immunoblot analysis of cleaved poly(ADP-ribose)polymerase. Pharmacologic inhibitors were used to manipulate caspases and c-Jun-NH(2)-terminal kinases (JNK). RESULTS: The methylselenol precursor methylseleninic acid (MSeA) increased the apoptosis potency of SN38, etoposide, or paclitaxel by several folds higher than the expected sum of the apoptosis induced by MSeA and each drug alone. The combination treatment did not further enhance JNK1/2 phosphorylation that was induced by each drug in DU145 cells. The JNK inhibitor SP600125 substantially decreased the activation of caspases and apoptosis induced by MSeA combination with SN38 or etoposide and completely blocked these events induced by MSeA/paclitaxel. The caspase-8 inhibitor zIETDfmk completely abolished apoptosis and caspase-9 and caspase-3 cleavage, whereas the caspase-9 inhibitor zLEHDfmk significantly decreased caspase-3 cleavage and apoptosis but had no effect on caspase-8 cleavage. None of these caspase inhibitors abolished JNK1/2 phosphorylation. A JNK-independent suppression of survivin by SN38 and etoposide, but not by paclitaxel, was also observed. In contrast to MSeA, selenite did not show any enhancing effect on the apoptosis induced by these drugs. CONCLUSIONS: MSeA enhanced apoptosis induced by cancer therapeutic drugs in androgen-independent PCA cells. In DU145 cells, the enhancing effect was primarily through interactions between MSeA and JNK-dependent targets to amplify the caspase-8-initiated activation cascades. The results suggest a novel use of methyl selenium for improving the chemotherapy of PCA. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/15788689/Methylseleninic_acid_potentiates_apoptosis_induced_by_chemotherapeutic_drugs_in_androgen_independent_prostate_cancer_cells_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15788689 DB - PRIME DP - Unbound Medicine ER -