New Chemotherapeutic Agents: Monoterpenes and Fatty Acid Synthase Inhibitors
New Chemotherapeutic Agents: Monoterpenes and Fatty Acid Synthase Inhibitors
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DOI：
10.5772/62283
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发表时间：
2016-09
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影响因子：
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通讯作者：
S. Murata
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作者：
S. Murata
结直肠癌(CRC)是世界上最常见的癌症之一。大约90%的结直肠癌死亡是由转移引起的，全身化疗是不能切除转移的结直肠癌患者最后的希望。尽管最近全身化疗的进展延长了不能切除的结直肠癌患者的生存时间，但化疗药物的有效性、成本和副作用仍需改进。使用植物、微生物或真菌衍生的天然产品用于医疗保健在全球范围内发挥着重要作用，例如在抗癌药物和抗生素方面。癌细胞在许多方面与正常细胞不同。与正常细胞不同，恶性肿瘤细胞中的大部分脂肪酸来自新生脂肪生成，这强调了内源性脂肪生物合成在恶性转化中的重要性。今天市场上有几种抗癌药物，如紫杉醇、长春花碱、长春花碱和凡蒙，它们的起源都可以追溯到植物。几种植物精油中的单萜类化合物具有药用价值。在体外和动物实验中，不同的单萜如二柠檬烯、香叶醇、1，8-桉叶素和紫苏醇(POH)对结直肠癌有效。脂肪酸合酶(FASN)是新生脂肪生成的关键酶，在包括结直肠癌在内的许多癌症中显著上调。在正常成人中，FASN主要在肝脏和脂肪组织等有脂代谢的细胞中表达。已发现FASN在包括结直肠癌在内的多种人类癌细胞中表达上调。癌细胞的脂肪生成提供了增殖和生存优势以及对化疗药物的耐药性。抑制针对FASN的脂肪生成在体外和体内选择性地诱导人类癌细胞的凋亡。FASN在癌细胞和正常细胞中的差异表达使FASN成为肿瘤治疗的合适靶点。药理作用的FASN抑制剂有蓝豆素、C75、C93、奥利司他、木犀草素、表没食子儿茶素没食子酸酯(EGCG)、三氯生、辣椒素、姜黄素等。©2016作者(S)。获授权者InTech。本章根据知识共享署名许可证(http://creativecommons.org/licenses/by/3.0)，)的条款分发，该许可证允许在任何媒体上不受限制地使用、分发和复制，前提是正确引用原始作品。在这一章中，我们讨论了单萜类和FASN抑制剂对新型化疗药物抗结直肠癌的作用。
Colorectal cancer (CRC) is one of the most common cancers in the world. Around 90% of CRC deaths are caused by metastasis, and systemic chemotherapy is the last hope for patients with unresectable metastases of CRC. Although recent systemic chemothera‐ py advances have prolonged survival in patients with unresectable CRC, the effective‐ ness, cost, and side effects of the chemotherapeutic agents still need to improve. The use of plant-, microbial-, or fungal-derived natural products for medical benefits is playing an important role globally, such as in anti-cancer drugs and antibiotics. The cancer cells are different from normal cells in many points. In contrast to normal cells, most of the fatty acids in malignant cells are derived from de novo lipogenesis that emphasizes the importance of up-regulation of endogenous lipid biosynthesis in malignant transformation. Several anti-cancer drugs available on the market today, such as Taxol, Oncovin, Navelbine, and Vumon, trace their origins to plants. Monoterpenes of several essen‐ tial oils from plants possess medical benefits. Various monoterpenes such as dlimonene, geraniol, 1,8-cineole, and perillyl alcohol (POH) are effective for CRC in in vitro and animal experiments. Fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, is significantly upregulated in many cancers including CRC. In normal adults, FASN is mainly ex‐ pressed in cells with lipid metabolisms such as liver and adipose tissues. The expression of FASN has been found to be up-regulated in various human cancer cells including CRC. Lipogenesis by cancer cells provides proliferative and survival advantages and drug resistance against chemotherapeutic agents. Inhibition of lipogenesis targeting FASN induces apoptosis selectively in human cancer cells both in vitro and in vivo. The differential expression of FASN between cancer cells and normal cells makes FASN a suitable target for cancer treatment. The pharmacological FASN inhibitors are cerulenin, C75, C93, orlistat, luteolin, epigallocatechin-3-gallate (EGCG), triclosan, capsaicin, curcumin, and so on. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In this chapter, we discuss the usefulness of monoterpenes and FASN inhibitors against CRC for the novel chemotherapeutic agents.