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  • br Shiromizu S Kusunose N Matsunaga N Koyanagi S

    2020-08-18


    23. Shiromizu S, Kusunose N, Matsunaga N, Koyanagi S, Ohdo S. Optimizing the dosing schedule of L-asparaginase improves its anti-tumor activity in breast tumor-bearing mice. J Pharmacol Sci. 2018;136(4):228e233.
    24. Terada T, Sawada K, Irie M, Saito H, Hashimoto Y, Inui K. Structural re-quirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2. Pflugers Arch Eur J Physiol. 2000;440(5):679e684. 25. Barretina J, Caponigro G, Stransky N, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012; 483(7391):603e607.
    26. Herrera-Ruiz D, Knipp GT. Current perspectives on established and putative mammalian oligopeptide transporters. J Pharm Sci. 2003;92(4):691e714.
    29. Gong Y, Wu X, Wang T, et al. Targeting PEPT1 : a novel strategy to improve the antitumor efficacy of doxorubicin in human hepatocellular carcinoma therapy. Oncotarget. 2017;8(25):40454e40468. 30. Ito K, Hikida A, Kawai S, et al. Analysing the substrate multispecificity of a proton-coupled oligopeptide transporter using a dipeptide library. Nat Com-mun. 2013;4:1e10. 
    32. Spanier B, Rohm F. Proton coupled oligopeptide transporter 1 (PepT1) function, regulation, and influence on the intestinal homeostasis. Compr Physiol. 2018; 8(2):843e869.
    Contents lists available at ScienceDirect
    European Journal of Pharmacology
    journal homepage: www.elsevier.com/locate/ejphar
    Full length article
    Bouchardatine suppresses rectal cancer in mice by disrupting its metabolic T pathways via activating the SIRT1-PGC-1α-UCP2 axis
    Yao-Hao Xua, Qin-Qin Songa, Chan Lia, Yu-Tao Hua, Bing-Bing Songa, Ji-Ming Yeb, Yong Raoa,∗, Zhi-Shu Huanga
    a Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China b Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, 3083 Australia
    Keywords:
    Bouchardatine
    Energy metabolism
    Cancer Maresin1 is an attractive target of the therapeutic strategy for cancer. The present study identified bouchardatine (Bou) as a potent suppressor of rectal cancer growth by cycle-arresting independent of apoptosis. In cultured HCT-116 rectal cancer cells, Bou increased glucose uptake/oxidation and capacity of mitochondrial oxidation. These effects were associated with an upregulation of uncoupling protein 2 (UCP2) and the activation of its upstream Sirtuin 1 (SIRT1)/(Liver kinase B1) LKB1- (Adenosine monophosphate-activated protein kinase) AMPK axis. The pivotal role of UCP2 in the cancer-suppressing effect was demonstrated by overexpressing UCP2 in HCT-116 cells with similar metabolic effects to those produced by Bou. Interestingly, Bou activated peroxi-some proliferators activated receptor γ coactivator 1α (PGC-1α) and recruited it to the promoter of UCP2 in HCT-116 cells along with deacetylation (thus activation) by SIRT1. The requirement of SIRT1 for the cancer-suppressing effect through the PGC-1α–UCP2 was confirmed by the reciprocal responses to Bou in HCT-116 with defected and overexpressed SIRT1. Whereas knockdown, mutation or pharmacological inhibition of SIRT1 all abolished Bou-induced deacetylation/activation of PGC-1α, the opposing effects were observed after over-expressing SIRT1. In mice, administration of Bou (50 mg/kg) also suppressed the growth of rectal cancer as-sociated with increases the UCP2 expression and mitochondria capacity in the tumor. Collectively, our findings suggest that Bou has a therapeutic potential for the treatment of rectal cancer by disrupting the metabolic path of cancer cells via activating the PGC-1α-UCP2 axis with SIRT1 as its primary target.
    1. Introduction
    Cancer growth involves genetic modifications and chromosomal rearrangements that promote unchecked proliferation and abrogate cell death. These activities rely on the reprogramming of glucose metabo-lism to the glycolytic path known as the Warburg effect (Cairns, 2015). The Warburg effect produces key substrates for unchecked proliferation (Sullivan and Chandel, 2014; Lee et al., 2017), and also provides a suitable microenvironment for cancer cells for migration and survival (Rani and Kumar, 2017; Pan et al., 2009; Zhang et al., 2013; Yadav and Chandra, 2013). In contrast, the energy production by oxidative phos-phorylation path through mitochondrial oxidation does not yield suf-ficient metabolites (such as lactate) favoring cancer growth. In this sense, cancer has been regarded as a disease of mitochondrial meta-bolism which includes mutation of mitochondrial genes and enzymes (Razungles et al., 2013; Luengo et al., 2017). It has been reported that