MK591, a second generation leukotriene biosynthesis inhibitor, prevents invasion and induces apoptosis in the bone-invading C4-2B human prostate cancer cells: implications for the treatment of castration-resistant, bone-metastatic prostate cancer
| Autor: | Ritisha Ghosh, Jagadananda Ghosh, Sivalokanathan Sarveswaran, Shravan Morisetty |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Indoles lcsh:Medicine Apoptosis Bone Neoplasms Prostate cancer Prostate Cancer stem cell Cell Line Tumor medicine Humans Neoplasm Invasiveness Neoplasm Metastasis lcsh:Science Multidisciplinary Cancer prevention business.industry lcsh:R medicine.disease 3. Good health Prostatic Neoplasms Castration-Resistant medicine.anatomical_structure Cell culture Cancer cell Immunology Cancer research Quinolines Leukotriene Antagonists lcsh:Q Signal transduction business Proto-Oncogene Proteins c-akt Signal Transduction Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 4, p e0122805 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Castration-resistant prostate cancer (CRPC) is a major clinical challenge for which no cure is currently available primarily because of the lack of proper understanding about appropriate molecular target(s). Previously we observed that inhibition of 5-lipoxygenase (5-Lox) activity induces apoptosis in some types of prostate cancer cells, suggesting an important role of 5-Lox in the viability of prostate cancer cells. However, nothing is known about the role of 5-Lox in the survival of castration-resistant, metastatic prostate cancer cells. Thus, we tested the effects of MK591, a second-generation, specific inhibitor of 5-Lox activity, on the viability and metastatic characteristics of CRPC cells. We observed that MK591 effectively kills the bone-invading C4-2B human prostate cancer cells (which bear characteristics of CRPC), but does not affect normal, non-cancer fibroblasts (which do not express 5-Lox) in the same experimental conditions. We also observed that MK591 dramatically inhibits the in vitro invasion and soft-agar colony formation of C4-2B cells. Interestingly, we found that treatment with MK591 dramatically down-regulates the expression of c-Myc and its targets at sub-lethal doses. In light of frequent over-activation of c-Myc in a spectrum of aggressive cancers (including CRPC), and the challenges associated with inhibition of c-Myc (because of its non-enzymatic nature), our novel findings of selective killing, and blockade of invasive and soft-agar colony-forming abilities of the castration-resistant, bone-metastatic C4-2B prostate cancer cells by MK591, open up a new avenue to attack CRPC cells for better management of advanced prostate cancer while sparing normal, non-cancer body cells. |
| Databáze: | OpenAIRE |
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