Indonesian Journal of Cancer Chemoprevention
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Cytotoxic Potential of Flavonoid from Nicotiana tabacum Leaves on MCF-7 Human Breast Cancer Cells
Flavonoid has potential bioactivity as anticancer agents. The flavonoid of cultivated tobacco (Nicotiana tabacum), locally known as “Kasturi”, leaves was screened for its cytotoxicity against MCF-7 human breast cancer cells and non-transformed Vero cells (African normal cell kidney line) in different concentrations. This study aimed to examine the cytotoxic potential of the flavonoid of Kasturi tobacco leaves against MCF-7 human breast cancer cells. Flavonoid obtained from methanolic extracts of Kasturi tobacco leaves, which have been purified from nicotine. The flavonoid of Kasturi tobacco leaves with concentrations of 20 to 640 μg/mL were exposed to MCF-7 and Vero cells for 24 h. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Flavonoid of Kasturi tobacco leaves with concentrations of 160 μg/mL decreased the MCF-7 cell viability more than 50%, with an inhibitory concentration 50 (IC50) value of 148.41 μg/mL. Meanwhile, it inhibited 50% of Vero cell viability at 255.35 μg/mL. The flavonoid of Kasturi tobacco leaves has cytotoxic activity on MCF-7 cells, and might be a potential alternative agent for human breast cancer therapy.Keywords: flavonoid, tobacco leaves, human breast cancer cells, anticancer activit
The Role of Curcumin on Apoptosis through The RASSF1A and Bax Pathways in Breast Cancer
Curcumin has been reported with an in vitro the cytotoxic effect on several human cancer cells. However, reports on the mode of action and detail mechanism of curcumin in breast cancer disease are limited. Hence, curcumin’s effect on the human breast cancer cell line MCF-7 and MDA-MB-468 was investigated. The MCF-7 and MDA-MB-468 breast cancer cells line were given curcumin in several doses. The anti-proliferation activity of curcumin was determined using the MTS cell viability test and caspase-3 activity was used to detect apoptosis using flowcytometry. The expression of Ras-association domain family 1 isoform A (RASSF1A) and Bax protein in cells was evaluated by ELISA analysis. Kruskal-Wallis followed by the Mann-Whitney test and the Spearman correlation tests were used to asses correlation among RASSF1A, Bax, and caspase-3. Cytotoxicity of curcumin on MCF-7 was lower than that of MDA-MB-468 (75.73 μg/mL and 380.79 μg/mL). The concentration of curcumin at 80 μg/mL induced apoptosis mainly through the intrinsic pathway by caspase-3 activation. Curcumin also showed an anti-proliferative activity as shown by the increase of RASSF1A and Bax protein. Curcumin mediates anti-proliferative and apoptotic effect through the activation of RASSF1A and Bax. Our research data adds information about the role of curcumin in epigenetic events through RASSF1A protein.Keywords: Bax, caspase-3, curcumin, MCF-7, MDA-MB-468, RASSF1
Extract of Yellow Root (Arcangelisia Flava (L.) Merr.) from Several Regions in Kalimantan: Alkaloid Content and Cytotoxicity towards WiDr Colorectal Cancer Cells
Yellow root (Arcangelisia flava (L.) Merr.) has been scientifically known to have potential as an antimalarial, antibacterial, antioxidant, and anticancer. The purpose of this study was to determine the profile of alkaloid content and cytotoxicity of yellow root extract from several regions in Kalimantan. The alkaloid content was tested using the thin layer chromatography (TLC) method with dragendorf reagent. Cytotoxic in vitro test was conducted against WiDr colorectal cancer cells using the 3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide (MTT) assay. Yellow roots were collected from Samarinda city, Banjarmasin city, Barito Timur regency, Malinau district, and Balikpapan City. The MTT inhibitory concentration 50 (IC50) of yellow root extracts were 573.308 μg/mL; 582.857 μg/mL; 296.326 μg/mL; 114.119 μg/mL; and 320.162 μg/mL respectively. Results of the compound identification indicated that alkaloid was found in A. flava from all regions. Alkaloids of A. flava extract should be investigated further in order to find possible active agent that could decrease the viability of WiDr colorectal cancer cells.Keywords: Arcangelisia flava, Borneo, colorectal cancer, Kalimantan, WiDr cells
Pentagamavunon-0 (PGV-0) Enhance Cytotoxic Effect of Doxorubicin through Increasing of Apoptosis, Senescence and ROS Level on Triple Negative Breast Cancer 4T1
TNBC, one of the sub type of breast cancers was widely known with high tumorigenic and poor prognosis than others. The development of combination agent (co-chemotherapy) with doxorubicin for chemotherapy of TNBC were carried out to decrease doxorubicin side effect and resistance in cancer. This present study aims to explore the co-chemotherapeutic properties of PGV-0 and investigate induction of doxorubicin on apoptosis, senescence and ROS against TNBC. 4T1 Cell line were used as a TNBC in vitro model. Cytotoxic measurement was performed using MTT assay resulting in IC50 values of 52 μM. Meanwhile, the combination of doxorubicin and PGV-0 showed synergistic effect which decreased cell viability of 4T1 better than single treatment of doxorubicin. Apoptosis analysis was performed using annexin V/PI assay indicated that the combination treatment of PGV-0 and doxorubicin increased apoptosis evidence. Senescence detection was carried out using senescence-associated-β galactosidase (SA-β-gal) assay. The results showed that a single treatment of PGV-0 induced cellular senescence and increased senescence cells in combination treatment. Moreover, DCFDA staining showed that PGV-0 increased ROS level at single treatment, whereas combination treatment increased ROS intracellular compared to the positive control of doxorubicin. Based on these results, PGV-0 has potential as a co-chemotherapeutic candidate on TNBC.Keyword: 4T1, PGV-0, Co-chemotherapy, Cytotoxic, Senescence, Apoptosis, RO
Cytotoxic Activity of Hyptis Pectinate Extracts on MCF-7 Human Breast Cancer Cells
Hyptis pectinata (L.) poit, popularly known in the world as “comb bushmint” is a medicinal plant commonly used for the treatment of throat and skin inflammations, bacterial infection, pain and cancer. The objective of this research is to determine the cytotoxic and antiproliferative effect under Hyptis pectinata ethanolic extract (HPE) treatment on breast cancer cells. The effect HPE of on cytotoxicity was examined by MTT assay on MCF-7 breast cancer cells. This assay also used to determine cell proliferation over 3 days of treatment with 1.5 – 100 µg/mL HPE. HPE showed that exhibited cytotoxic effects with IC50 value of 30 µg/mL for 24 hours and changes the physiological morphology on MCF-7 cells. Interestingly, the treatment of HPE for 48 and 72 hours highly decreases cell viability on MCF-7 with dose and time-dependent manner compared to untreated cells. These results indicate that HPE has antiproliferative activities and maybe the potential to be developed as a natural chemotherapeutic agent.Keywords: Hyptis pectinata (L.) poit extract, cytotoxicity, antiproliferative, MCF-7 cell
Free Radical Scavenging and In vitro Cytotoxic Activity of Bugnay (Antidesma bunius) Leaves Extract against A549 Human Lung Adenocarcinoma and HCT-116 Human Colorectal Cancer Cell Lines
Cancer is one of the significant causes of mortality worldwide. Studies on antineoplastic drugs focused on natural products have revealed several mechanisms to inhibit cancer cells. Bugnay (Antidesma bunius) leaves showed potentials due to its activity observed against brine shrimp and breast cancer cells. However, there is still limited knowledge about its activity against other human cancer cells. This study focused on determining the phytochemical compounds in A. bunius leaves extract, the free radical scavenging activity of the extract using the Diphenylpicrylhydrazyl (DPPH) method, and in vitro cytotoxic activity against two cancer cell lines, namely HCT-116 human colorectal and A549 human lung adenocarcinoma cancer cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The phytochemicals identified were unsaturated lactones, flavonoids, phenolics, diterpenes, saponins, tannins, carbohydrates, and reducing sugars. The extract showed significant free radical scavenging activity and a direct correlation of activity with concentration levels. It also exhibited cytotoxic activity against HCT-116 human colorectal and A549 human lung adenocarcinoma. Hence, A. bunius leaves have the potential to be a source of antioxidant and antineoplastic compounds. This warrant further isolation of the compounds for chemotherapeutic purposes.Keywords: Antidesma bunius, Bugnay, Cancer, Cytotoxicity, Radica
Growth of NIH 3T3 Fibroblast Cells Exposed to Carbonated Hydroxyapatite with Incorporated Propolis
Carbonated hydroxyapatite is frequently used as bone graft material in dentistry. It is highly biocompatible, has osteoconductive properties, and functions as a drug delivery system. Propolis is a natural product from bees that has antibacterial and anti-inflammatory effects and is capable of accelerating wound healing. Incorporating propolis into carbonated hydroxyapatite was expected to enhance the wound-healing process by stimulating fibroblast growth and regenerating alveolar bone in the treatment of periodontitis. The aim of this study was to evaluate the effect of carbonated hydroxyapatite with incorporated propolis on the viability of NIH 3T3 fibroblast cells. This study used three treatment groups [carbonated hydroxyapatite with various concentrations of incorporated propolis (5%, 7.5%, and 10%)] and one control group (carbonated hydroxyapatite with no propolis). An MTT assay was carried out to assess cell viability, and absorbance readings were performed by using an ELISA reader. The data were analyzed by using one-way ANOVA. The results showed significant differences between all groups, and carbonated hydroxyapatite with 10% incorporated propolis has the highest cell viability level of all groups, while the control group has the lowest cell viability. In conclusion, adding propolis to carbonated hydroxyapatite could increase the growth of NIH 3T3 fibroblast cells. Keywords: Carbonated hydroxyapatite, Propolis, NIH 3T3 fibroblast cells, MTT assa
Inhibition Capacity of the n-Hexane Fraction of Myrmecodia pendens as a Potential Anti-Cancer in Breast and Cervical Cancer: In Vitro Study
Breast cancer (BC) and cervical cancer (CC) have a high prevalence and mortality rate worldwide. Despite the availability of advanced treatment, resistance to conventional chemotherapies has emerged. Myrmecodia pendens, one of the species of Sarang Semut (local name), possess a potential of antitumor effects by inducing cell death different cancer cell entities. This study aimed to assess anti-tumor activities of n-hexane fraction of M. pendens in inhibiting cell survival and cell migration in BC and CC cells. M. pendens was extracted in methanol then fractionated using n-hexane or ethyl acetate. BC cells including MCF-7 (luminal A), HCC-1954 (HER2+) cells and CC Hela cells were treated with M. pendens extracts to evaluate cytotoxic activity using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay as well as anti-cell migration using scratch assay. We also analyzed inhibitory concentration 50 (IC50) of n-hexane fraction in BC and CC cells. We started with comparing cytotoxicity activities of methanol extract, ethyl acetate and n-hexane fractions of M. pendens. Data showed that the n-hexane fraction was the most potent inducing BC cell death. Therefore, we used the n-hexane fraction for further experiments. Interestingly, IC50 of this fraction in HCC-1954 and Hela cells were lower than in MCF-7 cells, 16; 13 and 60 ppm, respectively. Moreover, the low concentrations of n-hexane fraction inhibited HeLa cells migration, compared to control group (p<0.05). The n-hexane fraction of M. pendens shows promising anti-cancer agent, by inhibiting BC and CC cell survival as well as inhibiting CC cells migration.Keywords: breast cancer, cervical cancer, MTT assay, Sarang Semut, scratch assa
Revealing Chemopreventive Potential of Active Constituents from Medicinal Herbs Used in Indonesia for (Metastatic) Breast Cancer with Particular Molecular Targets
Breast cancer remains as one of the highest causes of cancer-related deaths in the world, including Indonesia. In spite of following the standard protocol therapy, some patients in developing countries consume medicinal herbs as an alternative, complementary, as well as supportive therapies. Several herbs have been recognized to be used for this purpose. Annona muricata, Curcuma longa, Curcuma zanthorrhiza, Curcuma zedoaria, Phyllanthus urinaria, Gynura procumbens, Garcinia mangostana, Morinda citrifolia, and Nigella sativa are some of the plants used as chemopreventive agents with several formulas. Various types of extracts of Annona muricata show anticancer activities in vitro and in vivo. Curcumin, obtained from Curcuma longa and Curcuma zanthorrhiza, acts as p53 regulator and pro-oxidant in MCF-7 cells and also acts as a fatty acid synthase inhibitor in MDA-MB-231 cells. Xanthorrhizol from Curcuma zanthorrhiza has pro-apoptotic activity via modulation of Bcl-2, p53, and PARP-1 protein levels. Curcuma zedoaria contains curcumenone, curcumenol and curdion, which show pro-apoptotic activity in various cell lines and a cancer-induced mouse model. Corilagin and geraniin from Phyllanthus urinaria have different pro-apoptotic effects, in which, the corilagin-caused apoptotic effect is mediated by extrinsic and mitochondrial pathways, whereas geraniin induces apoptosis via ROS-mediated stimulation, both in MCF-7 cells. Thymoquinone from Nigella sativa has been extensively studied for its anticancer activities in recent years. Plants are cultivated, collected and mixed depending on the use as herbal medicines. Active compounds might be formulated if deemed possible. The development of more potential derivatives is also necessary to produce more optimum anti-cancer agents. In conclusion, Indonesian plants and their active constituents show potential activities to be developed as chemopreventive agents.Keywords: Indonesian medicinal herbs, breast cancer, active constituents, molecular target
Study In Silico Compounds In 96% Ethanol Extract of Chrysanthemum cinerariifolium (Trev.) Leaves Towards Alfa Estrogen Receptors
Chrysanthemum cinerariifolium (Trev.) is a plant that has potential as an anticancer. This study aimed to predict the inhibitor of estrogen alpha and toxicity of compounds in 96% ethanol extract of C. cinerariifolium leaves in silico. Prediction of the activity of metabolic profiling compounds produced by UPLC QToF MS/MS ethanol extract 96% of C. cinerariifolium leaves towards alpha estrogen receptors (ER-α) (5W9C) was carried out using Molegro Virtual Docker. The docking results showed that the compound (2-Methyl-1,4-piperazinediyl) bis-[(3,4,5-trimethoxyphenyl)-methanone and Azoxystrobin have good activity compared to Tamoxifen, because these compounds have a lower Rerank Score. The activity of the test compound is also shown by the bonding of active amino acids (Arg 394, Asp351, Glu 353, and Val 533). As for the toxicity class based on Globally Harmonized System (GHS) and Lethal Dose 50 (LD50) values, the ten docking compounds had a relatively low toxicity.Keywords: C. cinerariifolium, breast cancer, alpha estrogen, cytotoxic activity, toxicit