340 triglyceride transfer protein (MTTP). MTTP is required for the assembly and secretion of TG-rich lipoproteins from both enterocytes and hepatocytes. MTTP inhibitor, JTT- 130, had been shown to lower plasma lipid mainly plasma TG [1]. The inhibition of MTTP gene expression, espe- cially in the intestine, may subsequently lead to reduction in the levels of cholesterol in blood. Other genes that were down-regulated in response to the extracts of the T. indica pulp were PDE3A, PTTG1 and CYP1A1. PDE3 is one of the phosphodiesterases (PDEs) that regulate intracellular concentrations of second mes- sengers, cAMP and cGMP, by catalysing the hydrolysis of their 30-50-phosphodiester bond [1]. The PDE3 family comprises 2 genes, the PDE3A and PDE3B. The PDE3A has higher afﬁnity towards cAMP than cGMP and is directly inhibited by cGMP [19]. Known inhibitors of the PDE3 include cilostamide and milrinone, but these inhib- itors do not differentiate between PDE3A and PDE3B [3]. The crude extracts of the T. indica fruit pulp suppressed the expression of only the PDE3A, by 5.1-fold, suggesting that the extracts contain bioactive compound(s) that is (are) selective inhibitor(s) of PDE3A. PTTG1 is an oncogene involved in cell cycle regulation and sister chromatid separation [31]. High levels of PTTG1 expression have been reported in various tumours including thyroid, pituitary, lung, colon, oesophagus, ovary and breast [16, 40, 47]. Studies had shown that nude mice developed cancer when subcutaneously injected with PTTG1-trans- fected cells [32]. CYP1A1 is one of the most important detoxiﬁcation enzymes, but it is also capable of generating carcinogenic intermediate metabolites from polycyclic aromatic hydrocarbons [20]. Resveratrol, an antioxidant widely found in fruits such as grapes, was found to inhibit the transcription of CYP1A1 in the HepG2 cells supposedly by preventing the activation of aryl hydrocarbon receptor [10]. Our microarray results showed that the crude extracts of the T. indica fruit pulp have the potential application as a chemotherapeutic agent for the treatment of cancer through the inhibition of the transcription of CYP1A1 and PTTG1 genes. In addition, a set of genes that are involved in reg- ulating the cell cycle checkpoints namely the cyclins, CCNG1, CCNG2, CCNA2, CCNB1, CCNB2 and CDC2 were also signiﬁcantly down-regulated. In conclusion, low concentration of T. indica fruit pulp extracts was able to signiﬁcantly regulate a total of 1501 genes. Amongst the up-regulated genes were those that code for the metallothioneins and glutathione S-transfer- ases which are well known for their stress response activ- ities. The extracts may act as hypolipidaemic agents by regulating the expression of APOA4, APOA5, ABCG5 and MTTP genes. The fruit pulp extracts also have anti-cancer potential by regulating genes involved in the cell cycle checkpoints. 123 Genes Nutr (2010) 5:331–341 Acknowledgments This study was funded by the following research grants: EScience Fund (12-03-02-2061) from the Ministry of Science, Technology and Innovation Malaysia (MOSTI), FRGS (FP004/2003C) from the Ministry of Higher Education Malaysia (MOHE), Postgraduate Research Fund (PS166/2008C) and Tutorship from the University of Malaya. We would like to thank Mr. Siah Eng Tian for the technical assistance on the microarray analysis. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. Aggarwal D, West KL, Zern TL, Shrestha S, Vergara-Jimenez M, Fernandez ML (2005) JTT-130, a microsomal triglyceride transfer protein (MTP) inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic tri- glycerides in guinea pigs. BMC Cardiovasc Disord 5:30 2. Berridge MV, Herst PM, Tan AS (2005) Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev 11:127–152 3. Bhattacharyya AK, Connor WE (1974) Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J Clin Invest 53(4):1033–1043 4. Bjorkhem I, Starck L, Andersson U, Lutjohann D, von Bahr S, Pikuleva I, Babiker A, Diczfalusy U (2001) Oxysterols in the circulation of patients with the Smith-Lemli-Opitz syndrome: abnormal levels of 24S- and 27-hydroxycholesterol. J Lipid Res 42(3):366–371 5. Bounous DI, Campagnoli RP, Brown J (1992) Comparison of MTT colorimetric assay and tritiated thymidine uptake for lym- phocyte proliferation assays using chicken splenocytes. Avian Dis 36(4):1022–1027 6. Cai L, Klein JB, Kang YJ (2000) Metallothionein inhibits per- oxynitrite-induced DNA and lipoprotein damage. J Biol Chem 275(50):38957–38960 7. Cao YH, Cao RH (1999) Angiogenesis inhibited by drinking tea. Nature 398(6726):381 8. Chan HM, Cherian MG (1992) Protective roles of metallothio- nein and glutathione in hepatotoxicity of cadmium. Toxicology 72(3):281–290 9. Chan PT, Fong WP, Cheung YL, Huang Y, Ho WK, Chen ZY (1999) Jasmine green tea epicatechins are hypolipidemic in hamsters (Mesocricetus auratus) fed a high fat diet. J Nutr 129(6):1094–1101 10. Ciolino HP, Daschner PJ, Yeh GC (1998) Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of the aryl hydrocarbon receptor. Cancer Res 58(24):5707–5712 11. Coyle P, Philcox JC, Carey LC, Rofe AM (2002) Metallothio- nein: the multipurpose protein. Cell Mol Life Sci 59(4):627–647 12. Del Bas JM, Ricketts ML, Baiges I, Quesada H, Ardevol A, Salvado MJ, Pujadas G, Blay M, Arola L, Blade C, Moore DD, Fernandez-Larrea J (2008) Dietary procyanidins lower triglyc- eride levels signaling through the nuclear receptor small hetero- dimer partner. Mol Nutr Food Res 52(10):1172–1181 13. Eaton DL, Bammler TK (1999) Concise review of the glutathione S-transferases and their signiﬁcance to toxicology. Toxicol Sci 49(2):156–164 14. Ezeh B, Haiman M, Alber HF, Kunz B, Paulweber B, Lingenhel A, Kraft HG, Weidinger F, Pachinger O, Dieplinger H, Kronen- berg F (2003) Plasma distribution of apoA-IV in patients with