Vol 10, Issue 4, 2017 Online - 2455-3891 Print - 0974-2441 INHIBITION OF CARCINOGENESIS BY SEED AND SOYBEAN MEAL EXTRACT IN COLON OF MICE: APOPTOSIS AND DYSPLASIA ANINDINI WINDA AMALIA 1 , KUSMARDI 2 , BERNA ELYA 1 , ADE ARSIANTI 3 * 1 Department of Phytochemistry and Pharmacognosy, Laboratory of Phytochemistry and Pharmacognosy, Faculty of Pharmacy, Universitas Indonesia, Indonesia. 2 Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Indonesia. 3 Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Indonesia. Email: arsi_ade2002@yahoo.com Received: 22 November 2016, Revised and Accepted: 30 December 2016 ABSTRACT Objective: Colon cancer is a major public health problem. Soybean has demonstrated chemopreventive and anticancer. Here, we have investigated the effect of a standardized seed and soybean meal extract (SE) with content of lunasin, here named grobogan extract (GE) and SE. They are botanical drug substance in experimental models of colon cancer in vivo. Methods: The effect of GE and SE was examined on the preneoplastic lesions (aberrant crypt foci), polyps and tumors induced by the carcinogenic agent azoxymethane (10 mg/kg) and dextran sodium sulfate 2% as well as in a xenograft model of colon cancer in mice. Results: GE and SE increased apoptosis (p=0.001). GE (150 mg/kg) has the highest impact level of apoptosis (p=0.009). GE and SE decreased dysplasia (p=0.024). GE (200 mg/kg) has the highest impact level of dysplasia (p=0.002), and SE (200 mg/kg) has the second impact level of dysplasia (p=0.003). Conclusions: GE and SE inhibition of colon carcinogenesis with increased level of apoptosis and decrease level of dysplasia. Keywords: Soybean, Lunasin, Colon cancer, Azoxymethane, Dextran sodium sulfate, Apoptosis, Dysplasia. INTRODUCTION Colorectal cancer (CRC) represents the third most common cancer in men (746,000 cases, 10% of the total) and the second in women (614,00 cases, 9.1% of the total) worldwide [1]. Almost 55% CRC occur in more developed country but it is inevitable this time the incidence of CRC increased in developing country. It is happened because of change in diet and lifestyle, among other: Increased consumption of red meat and processed foods, decreased consumption of foods containing fiber (fruits and vegetables), increased weight (obesity), low physical activity, smoking and high alcohol intake [1,2]. Pharmacoeconomic studies have highlighted a trend for rising cost associated with CRC, which is linked to the increasing use of targeted biological therapies [3]. Screening strategies are utilized but have not reduced disease incidence or mortality [4]. Furthermore, therapeutic intervention, which is by itself very toxic, may fail to prevent disease progression to metastatic disease [5]. Therefore, there is an interest in both cancer preventive strategies - which include experimentation with safe phytochemical agents - and new curative treatments [6]. Soybean (Glycine max) is an ancient legume consumed worldwide, but most commonly in Asian countries, such as China, Japan, Korea, Taiwan, and Indonesia. The demographic consumption pattern of soybean varies geographically with Asians utilizing (20-80 g/day), mostly in the forms of traditional soy foods and fermented soy foods, such as soybean, soy milk, tofu, tempeh, misso, natto, soybean paste, and soy sauce [7,8] as compared to Western population consuming meagerly (1-3 g/day), mostly in processed forms, such as soy drinks, breakfast cereals, energy bar and soy burger [9]. Epidemiological evidence has demonstrated an association between the consumption of soybean and improved health, particularly as a reduced risk for cardiovascular diseases [10] and cancer, such as breast, prostate, endometrial, lung, and bladder cancer [11-17]. Moreover, a number of animal models support anticancer properties of soy which constituents have been shown to suppress tumor growth in a variety of tissues including skin, bladder, mammary, and prostate [18]. In last decades, studies have isolated and identified an array of biologically active compounds or phytochemicals contained in soybean with cancer preventive effects. A likely candidate is lunasin, a novel cancer preventive peptide, the efficacy of which has been demonstrated in our laboratory [19-22]. Initially identified in soy, lunasin is also present in barley, a food crop known for its health effects [21]. Lunasin is a unique 43 amino acid soybean peptide that contains at its carboxyl end 9 Asp (D) residues, an Arg-Gly-Asp (RGD) cell adhesion motif, and a predicted helix with structural homology to a conserved region of chromatin-binding proteins. It has been shown to suppress carcinogenesis caused by chemical carcinogens and oncogenes in in vitro models and a mouse model for skin cancer [19-22]. Histone acetylation and deacetylation have been associated with eukaryotic transcriptional regulatory mechanisms [23]. The affinity of lunasin for hypoacetylated chromatin suggests a role in chromatin modification, a process implicated in cell cycle control and in the role of tumor suppressors in carcinogenesis [24]. Transfection of the lunasin gene into mammalian cells leads to mitotic arrest and cell lysis, resulting in lunasin bound to the chromatin [25]. Subsequently, we showed that exogenous addition of synthetic lunasin peptide to mammalian cells inhibits histone acetylation in the presence of sodium butyrate, a histone deacetylase inhibitor [22]. Because lunasin inhibits core H3 and H4 histone acetylationin mammalian cells [22], we propose an epigenetic mechanism whereby lunasin selectively kills cells that are being transformed or newly transformed cells by disrupting the dynamics of histone acetylation-deacetylation, which is triggered by the inactivation of tumor suppressors that operate through histone acetylation deacetylation [19]. © 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2017.v10i4.16276 Research Article