Sensitization of Tumor Cells toward Chemotherapy: Enhancing the Efficacy of Camptothecin with Imidazolines

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• 作者：Sharma ; Vasudha ; Lansdell ; Theresa A. ; Peddibhotla ; Satyamaheshwar ; Tepe ; Jetze J.
• 刊名：Chemistry & Biology
• 出版年：2004
• 出版时间：December, 2004
• 年：2004
• 卷：11
• 期：12
• 页码：1689-1699
• 全文大小：507 K

文摘

Activation of nuclear transcription factor κB (NF-κB) by chemotherapeutic agents was found to protect cells from apoptosis. In light of its central role in regulating the cellular resistance to apoptotic agents, inhibition of NF-κB-mediated gene transcription may sensitize tumor cells to chemotherapeutic agents and enhance their efficacy. We describe herein a noncytotoxic imidazoline scaffold that sensitizes leukemia T cells to the chemotherapeutic agent camptothecin. No significant induction of apoptosis was found when cells were treated with the imidazoline; however, pretreatment of cells with this agent resulted in a drastic enhancement in efficacy of camptothecin (75-fold). Elucidation of the potential cellular mechanism revealed that the imidazoline prevents nuclear translocation of NF-κB. These findings indicate that inhibition of NF-κB by this imidazoline may present improved strategies in the chemotherapeutic treatment of cancer.