Using natural products to promote caspase-8-dependent cancer cell death

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• 作者：Poonam Tewary ; A. A. Leslie Gunatilaka…
• 关键词：TRAIL ; Apoptosis ; Necroptosis ; Poly (I ; C) ; PIVAC15
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：66
• 期：2
• 页码：223-231
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Oncology; Immunology; Cancer Research;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-0851
• 卷排序：66

文摘

The selective killing of cancer cells without toxicity to normal nontransformed cells is an idealized goal of cancer therapy. Thus, there has been much interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a protein that appears to selectively kill cancer cells. TRAIL has been reported to trigger apoptosis and under some circumstances, an alternate death signaling pathway termed necroptosis. The relative importance of necroptosis for cell death induction in vivo is under intensive investigation. Nonetheless, many cancer cells (particularly those freshly isolated from cancer patients) are highly resistant to TRAIL-mediated cell death. Therefore, there is an underlying interest in identifying agents that can be combined with TRAIL to improve its efficacy. There are numerous reports in which combination of TRAIL with standard antineoplastic drugs has resulted in enhanced cancer cell death in vitro. However, many of these chemotherapeutic drugs are nonspecific and associated with adverse effects, which raise serious concerns for cancer therapy in patients. By contrast, natural products have been shown to be safer and efficacious alternatives. Recently, a number of studies have suggested that certain natural products when combined with TRAIL can enhance cancer cell death. In this review, we highlight molecular pathways that might be targeted by various natural products to promote cell death, and focus on our recent work with withanolides as TRAIL sensitizers. Finally, we will suggest synergistic approaches for combining active withanolides with various forms of immunotherapy to promote cancer cell death and an effective antitumor immune response.