Indonesian Journal of Cancer Chemoprevention
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A Mini-Review: Possible Mechanisms of Hepatoprotective Effect of Aloe Vera Gel
Full text linkProtective agent for hepatotoxicity is still a great challenge in the management of liver diseases. Aloe vera is a beneficial plant that has been studied for food supplements, cosmetic and herbal medicine. Aloe vera contains many compounds which have a role in body health including polysaccharides, phenolic, flavonoid, terpenoid, amino acid, and several minerals. There have been compelling evidences that natural phytochemicals and their derivatives have hepatoprotective activities. Information of the aloe vera and its mechanism of action for possible hepatoprotective activities, including in silico, in vitro, and in vivo studies were obtained from Pubmed, Science Direct, Scopus, and Google scholar search engines. This current review was focusing on the possible contribution of compounds inside aloe vera gel and the suggestion of its mechanism on protective effect, especially for liver. The complexity of monosaccharides composition, backbone structures, acetyl group, and molecular weight of aloe polysaccharides have possible correlations with its hepatoprotective effect. Most of the hepatoprotective mechanisms of aloe compounds are related to their protective effect against inflammation and oxidative stress. Several compounds may have combination effects or several targets lead to synergistic effects.Keywords: Aloe vera, food supplement, hepatoprotective, liver disease, mechanism of action
Addition of Beetroot Extract to Neoadjuvant Adriamycin Cyclophosphamide Regimen Increased Tumor Cell Apoptosis in Mammary Adenocarcinoma Rats
Full text linkApoptosis is one of the anticancer targets. Currently, the concomitant use of phytotherapy products and chemotherapy regimens is common in breast cancer patients. The purpose of this study was to examine the apoptotic effect of adding beetroot extract to the neoadjuvant Adriamycin Cyclophosphamide (AC) regimen by observing the expression levels of p53 and caspase 3 in tumor tissue from mammary adenocarcinoma rats. Twenty-four rats that succeeded in growing tumor nodules were randomly divided into 4 treatment groups: without treatment, AC only treatment, AC plus beetroot extract at dose of 25 and 100 mg/kg BW, respectively. AC was given 4 cycles in doses of 5 and 50 mg/kg body weight intraperitoneally every week. Tumor tissue was dissected at 4th week for examination of p53 and caspase 3 expression levels using the qRT-PCR method. The addition of beetroot extract at doses of 25 and 100 mg/kg BW in the neoadjuvant AC regimen showed significantly higher levels of p53 and caspase 3 expression than those with AC treatment alone. These results proved that beetroot extract has a synergistic effect with neoadjuvant AC regimen by increasing tumor cells apoptosis.Keywords: Beetroot extract, Adriamycin, Cyclophosphamide, apoptosis, p53
α-Mangosteen as An Oxidative Inhibitor in Hepatocellular Carcinoma
Full text linkHepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the second leading cause of cancer mortality worldwide. Many strategies to discover molecular-based therapy are currently being implemented to overcome the resistance in HCC treatment. Cancer research is more targeted at molecular level of natural ingredients treatment as chemoprevention to reduce carcinogenesis risk. One of the natural compounds that serve as chemopreventive agent is mangosteen. α-Mangosteen, a xanthone commonly found in the fruit hull of Garcinia mangostana Linn, possess as an antioxidant. This study aims to determine the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl (PC) as the biomarkers of oxidative stress on untreated HepG2 cells compared to α-mangosteen-treated HepG2 cells. The results indicated that α-mangosteen has a cytotoxic effect on HepG2 cells with IC50=242.58 μg/mL and reduced ROS level 23.15±4.29% at 200 μg/mL. The MDA level of HepG2 cells was not significantly higher than on WRL-68 by 7.6%, 17.93%, 28.8%, 35.32%, and 61.95% at 100, 200, 500, 800, and 1000 μg/mL respectively. α-Mangosteen at 100 and 200 μg/mL reduced protein carbonyl by 76.24 and 79.84% in HepG2 cells line while compared to normal liver cells line (WRL-68) significantly (P<0.05). In conclusion, α-mangosteen reduced levels of ROS, MDA and PC. Therefore, α-mangosteen is a potential anti-cancer agent through oxidative stress inhibition.Keyword: free radical, HepG2 cells, α-mangosteen, oxidative stress
Bone Resorption in Ameloblastoma and Its Underlying Mechanism
Full text linkAmeloblastoma, a tumor located in the jaw, grows slowly but locally invasive. Ameloblastoma expands in the jaw based on a mechanism resorbing the surrounding bone. To date, the bone resorption mechanisms of ameloblastoma are associated with the expression of receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANKL), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF)-α. RANKL plays an important role in generating osteoclastogenesis. MMPs degrade the extracellular matrix. TNF-α can induce the formation of osteoclast and modulate the MMPs. In this review the bone resorption mechanism of ameloblastoma as well its signaling pathway will be disclosed.Keywords: Ameloblastoma, RANKL, MMPs, TNF-α
Association between Vitamin D and Calcium Level and BMD Alteration in Post-Menopausal Osteoporosis Patients Treated with Bisphosphonate Therapy for at Least 1 Year in Saiful Anwar Hospital Malang
Full text linkPost-menopausal osteoporosis is a degenerative disease among post-menopausal women. In Indonesia, women over 50 years old get post-menopausal osteoporosis.The therapy should be comprehensive and continous. Bisphosphonate therapy is one of the most preferable therapeutic option for maintaining bone density. Calcium and vitamin D have a role in increasing osteoblastic activity. The objective of this study was to describe the vitamin D and calcium in bone mineral density (BMD) of hip and spine in postmenopausal woman with biphosphonat therapy. This study is a cross-sectional, observational analytic. The subject were female patients with post-menopausal osteoporosis treated in clinic of RSUD dr. Saiful Anwar Malang, who had received routine bisphosphonate for at least 1 year. The method was collecting the patient data, who received oral and injectie bisphosphonate therapy, serial BMD test,hip and spine, vitamin D and calcium level in serum test. Total sample 25 participan, the association between BMD change (Δ BMD), vitamin D and calcium level, were analyzed.with Chi Square test then continued using Spearman correlation test. Vitamin D levels in Δ BMD Spine in participants was less <30 ng/ml, mean 16.8+6.95 14 respondents (56%), and 6 respondens (24%) 10.05+5.28, normal vitamin D levels were 5 respondents (20%) mean 34.16+5.10. Vitamin D levels in Δ BMD Hip in participants was less <30 ng/ml, mean 15.19+7.7 12 respondents (48%), and 8 respondens (32%) 12.30+5.57, normal vitamin D levels were 5 respondents (20%) 33.66+5.40. Calcium levels in BMD spine 9.60+0.45, 14 respondents (56%), and 11 respondens (44%) 9.59+0.52. There is a significant and moderate relationship between vitamin D levels with Δ BMD spine (p=0.009, r=0.564) and Hip (p=0.039, r= 0.480) T Blood calcium levels with Δ BMD changes unrelated (normal). There is a significant association between vitamin D levels spine and Hip Δ BMD. Blood calcium levels with Δ BMD changes unrelated.Keywords: Osteoporosis, Bisphosphonate, Vitamin D levels, Calcium levels
Solanum nigrum Ethanolic Extract (SNE) Increases Cytotoxic Activity of Doxorubicin on MCF-7 Cell
Full text linkLeunca (Solanum nigrum L.) is a potential source of natural anticancer agents. Solanum nigrum L. ethanolic extract (SNE) has cytotoxic activity in several cancer cell lines. We aimed to evaluate the ability of SNE to increase MCF-7 cell sensitivity to doxorubicin as a chemotherapeutic agent for breast cancer. Cell viability of SNE and its combination treatment with doxorubicin were conducted by 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) assay, and apoptosis assay was analyzed by Ethidium bromide-acridine orange method. The SNE showed a cytotoxic effect in the MCF-7 cell line with IC50 50 μg/mL. Combination treated DOX-SNE resulted in a combination index (CI) value of 0.21, indicating strong synergism SNE and doxorubicin. The SNE 25 μg/mL combined with doxorubicin 100 nM optimally induced apoptosis of MCF-7 cells. We concluded that SNE is the potential to be developed as a co-chemotherapeutic agent through apoptosis induction though the molecular mechanism need to explore.Keywords: Solanum nigrum L. herb ethanolic extract, doxorubicin, MCF-7, apoptosis
Inhibition of Human Epidermal Growth Factor Receptor-2 (HER-2) from Pomelo (Citrus maxima) Flavonoid Compounds: an In Silico Approach
Full text linkCitrus maxima or pomelo is a plant that has potential as an anticancer because it contains flavonoids. One of the targets of breast anticancer receptors is the HER-2 protein. This research aims to determine the anticancer activity, the toxicity of the compound, and the prediction of physicochemical properties of flavonoids contained in Citrus maxima through in silico approach. Flavonoid compounds were screened using SwissADME with Lipinski's rule of five, Torsion, TPSA, and P-Gp Non-Substrate. Compounds that passed the screening were carried out molecular docking to the HER-2 receptor (PDB ID: 3PP0) using the Molegro Virtual Docker (MVD). The HER-2 receptor (GDP ID: 3PP0) was declared valid because it had RMSD<2Å. The results showed that there were 11 flavonoid compounds that passed the screening and had a lower rerank score than the comparison compound Trastuzumab. Toxicity was predicted using the Protox II online tool and the results showed that the flavonoid compounds were in the safe limits, namely classes 5 and 3. Based on this research, it can be concluded that acacetin, diosmetin, honyucitrin, isosinensetin, nobiletin, sinensetin, and tangeretin can be candidates for breast cancer drugs based on natural ingredients.Keywords: breast cancer, Citrus maxima, HER-2, in silico
Recloning and Characterization of C2C12 Myoblast and Its Clonal Derivatives
Full text linkThe C2C12 myoblasts are adult murine muscle stem cells which isolated after injury to induce muscle regeneration. The cells are widely used in pharmaceutical and biological researches to represent skeletal muscle cells. In our laboratory, we utilize the cells for glucose uptake assay after insulin treatment and studying the muscle regeneration. In this study we conducted recloning of C2C12 cells by limiting dilution cloning (LDC) and investigated the biological properties incuding cell proliferation, adhesion and differentiation of the clonal cells in comparison to the parental cells. Cell proliferation rate had been determined by WST assay, cell adhesion had been observed after cell detachment by EDTA and cell differentiation into multinucleated myotube had been investigated after induction and incubation with horse serum. As results, two clonal derivatives of C2C12 myoblast cells had been retrieved by LDC and used for cell assays. Moreover, the results indicated that parental cells showed faster proliferation rate and better differentiation ability than that of clonal cells. In the contrary the parental cells exhibited weaker adhesion rate than clonal cells. To conclude, C2C12 parental cells are better for performing the glucose uptake or muscle regeneration assays since they showed better differentiation capability.Keywords: C2C12 cells, cells differentiation, myoblast, myotube, recloning
Bioinformatics Analysis of Rho GTP-ase Activating Protein 35 (ARHGAP35) in Breast Cancer Migration
Full text linkBreast cancer is a second deadly cancer after lung cancer worldwide. Progression of cancer is driven by mutated cancer drive gene such as ARHGAP35. This study aims to analyze the role of ARHGAP35 in the growth and development of breast cancer cells. ARHGAP35 expression level was analyzed using Oncomine (p-value<1E-4; gene rank top 10%). Overall survival (OS) and disease-free survival (DFS) were evaluated by using GEPIA (median cutoff; HR displayed with 95% CI). STRING was used for analyzing the protein-protein interaction network, while WEBGESTALT for KEGG pathway and gene ontology (GO) of ARHGAP35 and associated proteins and cBioPortal for gene mutation. ARHGAP35 was overexpressed in several types of breast cancer, namely invasive ductal breast carcinoma (IDC), invasive ductal and lobular breast carcinoma (IDLC), invasive lobular breast carcinoma (ILC), male breast carcinoma, and mixed ductal and lobular carcinoma (MDLC). High expression of ARHGAP35 had significantly lower OS (p=0.045) compared to low expression of ARHGAP35 and the difference in DFS was not significant (p=0.98). ARHGAP35 interacted with RHOA, RHOB, RHOC, RHOD, RASA1, RND1, RAC1, CDC42, FYN and SRC. KEGG pathway and GO analysis showed that these proteins are highly involved in actin-based processes through adherent junction, axon guidance, focal adhesion, regulation of actin cytoskeleton, and tight junction. Mutation rate analysis showed 34 missense, 29 truncating, 3 fusion, and 1 in frame on ARHGAP35. Taken together, ARHGAP35 may involve in the growth and development of breast cancer through regulation of actin cytoskeleton pathway.Keywords: ARHGAP35, breast cancer, KEGG pathway, mutation rate, actin cytoskeleton
Antioxidant and Cytotoxic Activities of Lactic Acid Bacteria on Colorectal Cancer WiDr Cell Line
Full text linkColorectal cancer (CRC) is one of the leading causes of cancer and cancer-related deaths worldwide. Lactic acid bacteria (LAB) are bacteria that have potential activity as an inhibitor of the growth of colorectal cancer, and also has been widely used and was very useful for consumption. In our previous study, we isolated various LAB from Indonesian traditional fermented food. This study aims to determine the potential of LAB as an anticancer agent by determining the antioxidant activity and cytotoxicity assay of colon cancer in the WiDr cell line. This study used extracellular extract of various LAB. We use the Diphenylpicrylhydrazyl (DPPH) method to determine the antioxidant activity and 3-(4,5'dimethylihiazol-2-yl),2.5-di-phenyl-relrrzolium bromid (MTT) assay to study cytotoxicity activity. The viability cell staining also applied to detect unviable cells. The results informed that the highest antioxidant activity was shown by S.34 LAB with 81% activity. The S.34 also showed cytotoxicity activity with 73% of WiDr viable cell at a concentration of 200 μg/mL of LAB extract. Based on the results of the study, it can be concluded that the S.34 LAB from Bekasam may inhibit the proliferation of WiDr cell lines and It had the highest antioxidant activity comparing to other LAB samples.Keywords: Lactic Acid Bacteria, colorectal cancer, anticancer, antioxidant, WiDr cells