Combination of Proteasomal Inhibitors Lactacystin and MG132 Induced Synergistic Apoptosis in Prostate Cancer Cells
| Autor: | Robert B. Shirley, Vijayabaskar Lakshmikanthan, Ronald W. Lewis, M. Vijay Kumar, Dimpu M. Patel, Ismail Kaddour-Djebbar |
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| Jazyk: | angličtina |
| Předmět: |
Male
Cancer Research MG132 Leupeptins Lactacystin Cysteine Proteinase Inhibitors Pharmacology Biology lcsh:RC254-282 chemistry.chemical_compound Antineoplastic Combined Chemotherapy Protocols LNCaP Tumor Cells Cultured medicine Humans Bortezomib NF-kappa B Prostate apoptosis Prostatic Neoplasms Drug Synergism lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Acetylcysteine I-kappa B Kinase Mechanism of action Proteasome chemistry Apoptosis proteasomal inhibitors Proteasome inhibitor medicine.symptom Proteasome Inhibitors Research Article medicine.drug |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 7, Iss 12, Pp 1104-1111 (2005) |
| ISSN: | 1476-5586 |
| DOI: | 10.1593/neo.05520 |
| Popis: | The proteasome inhibitor Velcade (bortezomib/PS-341) has been shown to block the targeted proteolytic degradation of short-lived proteins that are involved in cell maintenance, growth, division, and death, advocating the use of proteasomal inhibitors as therapeutic agents. Although many studies focused on the use of one proteasomal inhibitor for therapy, we hypothesized that the combination of proteasome inhibitors Lactacystin (AG Scientific, Inc., San Diego CA) and MG132 (Biomol International, Plymouth Meeting, PA) may be more effective in inducing apoptosis. Additionally, this regimen would enable the use of sublethal doses of individual drugs, thus reducing adverse effects. Results indicate a significant increase in apoptosis when LNCaP prostate cancer cells were treated with increasing levels of Lactacystin, MG132, or a combination of sublethal doses of these two inhibitors. Furthermore, induction in apoptosis coincided with a significant loss of IKKalpha, IKKbeta, and IKKgamma proteins and NFkappaB activity. In addition to describing effective therapeutic agents, we provide a model system to facilitate the investigation of the mechanism of action of these drugs and their effects on the IKK-NFkappaB axis. |
| Databáze: | OpenAIRE |
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