Indonesian Journal of Cancer Chemoprevention
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Anti-metastatic Activity of Curcumin Analog Pentagamaboronon-0-Sorbitol Against HER2-overexpressed MCF-7 Breast Cancer Cells
Breast cancer with Human Epidermal Growth Factor Receptor (HER)2 overexpression increases tumor progession and lead to metastasis, which is primarily cause of mortality in breast cancer. Pentagamaboronon-0 Sorbitol (PGB-0-So) is an aquoeous formulation of curcumin analog, PGB-0, with sorbitol. This compound has been developed as an anti-cancer chemotherapeutic agent and a boron carrying pharmaceutical for boron neutron capture therapy (BNCT). The aims of this study are to investigate antimetastatic activities of PGB-0-So against HER2-overexpressed MCF-7 breast cancer (MCF-7/HER2) cells. The MTT cytotoxicity assay of PGB-0-So exhibited cytotoxic effect with an IC50 value of 35 μM. The testing of anti-migration activity using the scratch wound healing assay demonstrated that PGB-0-So inhibited the closure of the wound on MCF-7/HER2 cells compare to the control. Furthermore, PGB-0-So was able to suppress matrix metalloproteinase (MMP)-9 activities, based on the gelatin zymography assay. In conclusion, PGB-0-So has potency to be developed as an anti-cancer agent against metastatic breast cancer.Keywords : PGB-0-So, anti-metastatsis, cell migration, MMP-9, MCF-7/HER
The Effect of Liberica Coffee on Liver Physiology and Histological Appearance of White Mice
Indonesia is one of the world's top coffee producing and exporting countries. Liberica coffee was one of the most widely cultivated types of coffee in Indonesia, especially in Tanjung Jabung Barat Jambi Province. Liberica coffee known as the coffee with highest levels of caffeine if compared with Arabica and Robusta coffee but the research about Liberica coffee was still very little if compared to the other two types of coffee. In the previous research, caffeine shown to be increasing alanine aminotransferase enzyme. Otherwise, coffee also contain chlorogenic acid which is a potent antioxidant and play a role in the protection of liver. The aim of this study are to investigate the effect of dark roasted Liberica coffee consumption on liver histological appearance, macroscopic anatomy and physiological function (serum glutamic-pyruvic transaminase (SGPT) level). This was an experimental study with posttest only control group design, using 45 male white mice and divided into 4 groups: control (with no coffee treatment), P1, P2 and P3 which were given coffee treatment consecutively 8000 ppm; 10.000 ppm and 12.000 ppm for 28 days. The result showed that liver histological damage level associated with the extent coffee intake. Although, the damage shown is still in a low level and has no impact in increasing SGPT level.Keywords : Liberica coffee, Liver, Histological appearance, SGPT leve
Ethyl Acetate Fraction of Caesalpinia sappan L. Enhances Cisplatin’s Cytotoxicity on HeLa Cells via G1 and S Arrest through p53 Expression
Cisplatin (cisp) is the first line chemotherapeutic agent for several cancer diseases which can cause significant side effects and cellular resistance. Combination-chemotherapy treatment (co-chemotherapy) was reported to be able to reduce cisp effects. Therefore, this study was carried out to investigate the cytotoxic activity of ethyl acetate fraction of C. sappan (EFC) in combination with cisp by observing apoptosis induction and cell cycle profile. Cytotoxic activity was evaluated by MTT assay. Cell cycle and apoptosis analysis were performed using flow cytometry and p53 expression was analyzed using immunocytochemistry. EFC performed cytotoxic effect on HeLa cells by showing morphological changes such as cell shrinkage, rounding and decreasing of cells viability in concentration dependent manner, giving IC50 value of 65 μg/mL. Combination of EFC and cisp in low concentration decreased cell viability into 36.86%. Further assay indicated that this combination caused redistribution of cell cycle arrest in G1 and S phases through p53 stabilization in nucleus. However, that mechanism was not followed by apoptosis. These results provide evidence to support EFC development as the enhancer of cisp effect, by improving its cytotoxicity on HeLa cells. EFC increases HeLa cells sensitivity to cisp through G1 and S cells’ arrest depending on p53 expression. Key words: co-chemotherapy, EFC, cervix cancer HeLa cells, p53, G1 and S arrest.
Methanolic Extract of Red Betel Leaves (Piper crocatum Ruiz & Pav) Perform Cytotoxic Effect and Antimigration Activity toward Metastatic Breast Cancer
Breast cancer is one type of cancer with a high mortality rate due to its metastatic property. Red betel leaves (Piper crocatum Ruiz and Pav) has been known as herbal medicine containing biophenolic, such as apigenin and luteolin derivatives which has cytotoxic activity toward cancer cells. This study is intended to explore the inhibitory effect of Piper crocatum leaves methanolic extract (PCM) on cell proliferation and migration by using 4T1 cells as model of metastatic breast cancer. By using MTT assay, PCM performed cytotoxic activity in a dose dependent manner with IC50 value of 120 μg/mL. Wound healing assay revealed that migration inhibitory activity of PCM on 4T1 cells at the concentration of 30 µg/mL. In conclusion, PCM perform cytotoxic effect and antimigration activity toward metastatic breast cancer cells.Keywords : breast cancer cells, Piper crocatum Ruiz & Pav, cytotoxic, cell mgratio
Phaleria macrocarpa Fruit Extract Inhibits NF-ĸB Activation and Apoptosis Induction on HeLa Cells
NF-κB is a transcription factor and if activated, it induces apoptosis inhibition. Phalerin from Phaleria macrocarpa fruits expected to inhibit NF-κB activation. This research is to investigate anticancer mechanism of Phaleria macrocarpa fruits extracts (EBMD) in NF-κB pathway. Molecular docking assay was performed to determine phalerin affinity to IKK. Cytotoxic activity was observed by MTT assay. Double staining was performed to determine the apoptotic cells. Docking score of phalerin to IKK is -60. The IC50 value of EBMD is 629 μg/mL. Apoptosis profile shows (shown that) many cells undergoing apoptosis after treatment. Thus, EBMD potentially inhibits activation of NF-κB pathway and triggers apoptosis on HeLa cells.Keywords : NF-κB, Phaleria macrocarpa, sel HeLa, Bcl-2, IKK, molecular dockin
Anti-Breast Cancer Potency of Multistage Extraction from Jamur Dewa (Agaricus blazei Murill) Solvents on MCF-7 Cells
ABM (Agaricus blazei Murill) is a basidiomycetes fungus. ABM is used by people for the treatment of diabetes, antihypertention, anticholesterol, anticancer, and immunostimulant. ABM contains terpene, steroids, agaritine, vitamin C, vitamin E, and betaglucane. In this research, ABM extract was tested as an anti-breast cancer in vitro using MCF-7 breast cancer cells. The extract was obtained from the multistage extraction process of several solvents in turn, the solvent used, among others, n-hexane, dichloromethane (DCM), chloroform, ethyl acetate, butanol, and water. The results of the research were the obtained IC50 value from n-hexane extract 247,17 μg /ml; extract DCM 227μg/ml ; chloroform extract 215,64 μg /ml ; extract of ethyl acetate 234,9 μg/ml ; butanol extract 500,78 μg/ml; while the water extract was inactive. Based on these results can be considered for further research to fractionate in order to know which class compounds have the potency as anticancer within the extracts.Key words : Agaricus blazei, multistage extraction, MCF-7 cells
Cinnamomum Essential Oil Prevents DNA Damage-Induced by Doxorubicin on CHO-K1 Cells
DNA damage usually happens due to the several chemical materials that induce genotoxic effect in normal cells. Cinnamon essential oil (CEO), which contains cinnamaldehyde as its major compound, has been reported to possess antioxidant activity to prevent DNA damage. The aim of this study is to evaluate the genotoxic and cytotoxic effect of CEO on doxorubicin-induced Chinese Hamster Ovary (CHO-K1) cells. The cytotoxic effect of CEO was determined by MTT assay with the parameter of IC50 while the genotoxic effect was carried out by micronucleus (MN) assay by using acridine orange fluorescent staining with the parameter of MN/1000 cells reduction number. Based on MTT assay, CEO showed cytotoxic activity with the IC50 value of 30 μg/ml and for MN assay, 3 μg/ml (1/10 IC50) of CEO decreased the percentage of micronucleus per 1000 cells up to 94,55%. Thus, the result can be summarized that CEO does not induce genotoxic and has the potency to prevent DNA damage caused by doxorubicin on CHO-K1 cells.Keywords: genotoxic, cinnamomum essential oil (CEO), micronuclei assay, in vitr
A Comparison of Antimetastatic Activity between Nerium indicum and Cinnamomum burmannii on 4T1 Cells
Metastatic process becomes a major problem in advanced cancer cases. Natural compounds found in several plants in Indonesia have a potency to be developed as chemoterapeutic agent which are targeted to metastatic process. Jure leaves (Nerium indicum) which contain oleandrin and cinnamaldehyde in cinnamon bark (Cinnamomum burmannii) reported to have cytotoxic activity on several cancer cells, but their activities on metastasic process have never been explored. This research aims to reveal and to compare their anti-metastatic effect toward 4T1 breast cancer cells. The cytotoxicity of jure leaves extract (JLE) and cinnamon essential oil (CEO) was obtained by MTT assay. Metastatic process mainly on cell migration was examined by scratch wound healing assay while MMP-9 expression that described the invassion process was observed by gelatin zymography assay. Molecular interaction between their active compounds and MMP-9 receptor was predicted by molecular docking. The result showed that treatment with JLE and CEO inhibited the growth of 4T1 cells with IC50 value of 125 µg/mL and 2.5 µg/mL, respectively. In addition, JLE performed inhibitory effect of cell migration better than CEO. Meanwhile, both JLE and CEO decreased MMP-9 protein expression. Thus, JLE and CEO have potentials to be developed as an anti-metastatic agent and JLE could be more effective.Key words: Nerium indicum, Cinnamomum burmannii, anti-metastasis, scratch assay, gelatin zimograph
Doxorubicin Induces Lamellipodia Formation and Cell Migration
Breast cancer is the main cause of cancer death among women, especially breast cancer metastasis. Metastasis process begins with the ability of cell cancer invasion. Doxorubicin, a antracycline chemotheraphy, is known to induce TGFβ1, thus promote invasion. The aim of this study is to optimize doxorubicin doses to induce lamellipodia formation in 4T1 and MCF-7/HER2 cells. Lamellipodia formation was observed by morphological changes using microscope inverted. The effect of doxorubicin on cell viability was analyzed using MTT assay. Rac1 expression after doxorubicin exposure was determined by western blotting. Lamellipodia formation was observed by morphological change of the cell at the dose 10, 25, 50 and 100 nM. Doxorubicin at the dose of 10 nM could induced lamellipodia formation without affect cell viability in both 4T1 and MCF-7/HER2 cells. Doxorubicin induced cell cycle arrest at G2/M phase at all doses. Doxorubicin 10 nM also decrease Rac1 expression compared to control.Key words: Doxorubicin, lamellipodia, Rac1, migration
Different 4T1 Cells Migration under Caesalpinia sappan L. and Ficus septica Burm.f Ethanolic Extracts
Secang (C. sappan L.) and awar (F. septica Burm.f) are known of Indonesian traditional medicine that highly consumed throughout centuries in order to cure various diseases. Recently, researchers also concern about its effects as anti-cancer on various cell types. This study was conducted to understand the ethanolic extract of C. sappan L. (ECS) and F. septica Burm.f (EFS) effects on 4T1 cells migration at various concentrations. Firstly, we examine cell proliferation profile with MTT assay under treatment with the extracts and obtained the IC50 value of ECS (20 μg/mL) and EFS (15 μg/mL). Subsequent assay conducted was to examine the cells migration under low concentration resulting in the migration inhibitory effect of both EFS and ECS with different intensity. EFS performed better migration inhibitory effect than ECS. Finally, we conducted gelatin zymography and western blot and revealed that the migration inhibitory effect of EFS may correlate to the lowering of protein expression of MMP9 and Rac-1 after 24 hours of treatment. We conclude that both extracts are potential to be developed as anticancer agent and EFS is more potent for anti-metastasis.Keywords: C. sappan L., F. septica Burm.f, 4T1, anti-migratio