Logo image
Back
Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells
Journal article   Open access   Peer reviewed

Methylseleninic acid potentiates apoptosis induced by chemotherapeutic drugs in androgen-independent prostate cancer cells

HONGBO HU, CHENG Jiang, Clement IP, Youcef M Rustum and JUNXUAN LÜ
Clinical cancer research, Vol.11(6), pp.2379-2388
2005
DOI: 10.1158/1078-0432.CCR-04-2084
PMID: 15788689
url
https://doi.org/10.1158/1078-0432.CCR-04-2084View
Published (Version of record) Open Access

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-associaied 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-NH2-terminal kinases (JNK). Results: The methylselenol precursor methylseleninic acid (MSeA) increased the apoptosis potency of SN38, etoposide, or pactitaxel 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 phosphorylatlon 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-independet 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. ©2005 American Association for Cancer Research.
 Antineoplastic Agents Tumors Biological and medical sciences Gynecology. Andrology. Obstetrics Male genital diseases Medical sciences Nephrology. Urinary tract diseases Pharmacology. Drug treatments Tumors of the urinary system Urinary tract. Prostate gland

Details

Metrics

12 Record Views
77 Times Cited - Web of Science
Logo image