دورية أكاديمية
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.
| العنوان: | 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. |
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| المؤلفون: | Sarveswaran, Sivalokanathan, Ghosh, Ritisha, Morisetty, Shravan, Ghosh, Jagadananda |
| المصدر: | Urology Articles |
| بيانات النشر: | Henry Ford Health Scholarly Commons |
| سنة النشر: | 2015 |
| المجموعة: | Henry Ford Health System Scholarly Commons |
| مصطلحات موضوعية: | Apoptosis, Bone Neoplasms, Cell Line, Tumor, Humans, Indoles, Leukotriene Antagonists, Male, Neoplasm Invasiveness, Neoplasm Metastasis, Prostate, Prostatic Neoplasms, Castration-Resistant, Proto-Oncogene Proteins c-akt, Quinolines, Signal Transduction |
| الوصف: | 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. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://scholarlycommons.henryford.com/urology_articles/232Test; https://scholarlycommons.henryford.com/context/urology_articles/article/1253/viewcontent/MK591.pdfTest |
| الإتاحة: | https://scholarlycommons.henryford.com/urology_articles/232Test https://scholarlycommons.henryford.com/context/urology_articles/article/1253/viewcontent/MK591.pdfTest |
| رقم الانضمام: | edsbas.15D55D39 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |