New Chemotherapeutic Agents: Monoterpenes and Fatty Acid Synthase Inhibitors

Abstract

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 chemotherapy advances have prolonged survival in patients with unresectable CRC, the effectiveness, 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 essential 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 expressed 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. In this chapter, we discuss the usefulness of monoterpenes and FASN inhibitors against CRC for the novel chemotherapeutic agents.