Indonesian Journal of Cancer Chemoprevention
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Cytotoxic and Apoptotic-inducing Effect of Fraction Containing Brazilein from Caesalpinia sappan L. and Cisplatin on T47D Cell Lines
Anticancer activity of secang’s heartwood (Caesalpinia sappan L.) is based on its main compound: brazilin and brazilein. Brazilin, brazilein, and other compounds such as caesalpiniaphenol can affect proteins that have a role in apoptosis. In this study, we observed cytotoxic activity of fraction containing brazilein (FCB) alone or in combination with chemotherapeutic agent, cisplatin and the ability of the combination to induce apoptosis in T47D breast cancer cell lines. Cytotoxicity assay was determined using MTT assay, whereas the detection apoptosis induction was conducted using flow cytometry using Annexin-V and propidium iodide. FCB and cisplatin showed cytotoxic effect on T47D cells with IC50 value of 68 µg/mL and 16 µM, respectively. Combination of FCB and cisplatin result synergistic combination at the concentration ratio of 1/2 IC50 with CI value of 0.66. Its combination also able to induce apoptosis on T47D cell population 13% larger than the single treatment. Based on this study, we conclude that FCB is able to enhance the cytotoxic effects of cisplatin by inducing apoptosis.Keywords: Caesalpinia sappan L., cisplatin, apoptosis, breast cance
Cytotoxic Activity of 1-(2,5-dihydroxyphenyl)-3-pyridine-2-yl-propenone on Colon Cancer Cell WiDr
Colon cancer is one of the most common death-caused cancer. The high mortality rate indicates that chemotherapy has not overcome cancer disease. Strategies and development of colon cancer treatment should be pursued. Compound 1-(2,5-dihydroxyphenyl)-3-pyridine-2-yl-propenone is the 2ʹ,5ʹ-dihydroxychalcone derivative, of which the B ring was substituted with 2-pyridine ring. Chalcone and its derivatives have been reported to have several biological activities, such as cytotoxic, anti-inflammatory, antiHIV, and as a tyrosine kinase inhibitor. The objectives of this research was to determine the cytotoxic activity on WiDr colon cancer cells of 1-(2,5-dihydroxyphenyl)-3-pyridine-2-yl-propenone. Cytotoxic activity was measured using MTT assay. Compound 1-(2,5-dihydroxyphenyl)-3-pyridine-2-yl-propenone inhibited WiDr cell growth with the IC50 of 16 µM. Morphology of WiDr cell showed that compound 1-(2,5-dihydroxyphenyl)-3-pyridine-2-yl-propenone inhibited cell growth in dose dependent.Keywords: compound 1-(2,5-dihydroxyphenyl)-3-pyridine-2-yl-propenone, WiDr colon cancer cell line, cytotoxic activit
Cardioprotective Effect of Kelor (Moringa oleifera) Leaf Ethanolic Extract against Doxorubicin-Induced Cardiotoxicity in Rats
The usage of doxorubicin (DOX) as an anticancer drug in cancer patient may cause several side effects. One of that is cardiotoxicity by inducing the expression of nitric oxide synthase which may release nitric oxide (NO) resulting reactive oxygen species (ROS) in the cardiac. DOX needs to be combined with antioxidant since it could supressed ROS in the cardiac and reduce cardiomyopathy. Kelor (Moringa oleifera) is known as the source of antioxidant. This study aim to observe the treatment effects of ethanolic extract of kelor (EEK) on histopathology profile and concentration of NO in rats cardiac. The result from the hematoxylin-eosin staining showed that EEK improved the histopathology profile of rats’ cardiac. Compared with the DOX-only treatment, the structure of cardiac muscle cells treated by ethanolic extract of kelor is more well-arranged and the cells’ nucleus still visible. Concentration of NO was measured by cardiac puncture method. The result showed that the concentration of NO was decrease in line with increasing dose levels of EEK in combination with DOX. But at rats only given with EEK, the concentration of NO is quite high. In conclusion, EEK could be a cochemotherapy agent by reducing the cardiotoxicity effect of DOX.Keywords : doxorubicin, Moringa oleifera, nitric oxyde, histopathology
SMEDDS of Citrus hystrix ethanolic extract improves cardiac and hepar histopathology profile on doxorubicin-induced rats
Citrus hystrix D.C. (kaffir lime) peel contains several flavonoids including rutin, naringenin, hesperidin. C. hystrix peel ethanolic extract (ChEE) has shown its potency as cardioprotector agent in chemotherapy. However, there are limitations to the utilization of ChEE due to its poor water solubility and low oral bioavailability. Accordingly, self-microemulsifying drug delivery system (SMEDDS) formulations were developed to improve the oral absorption of flavonoids. Tween 80, Corn oil, and propylene glicol (5:1:1ml) were combined to form ChEE-SMEDDS. The present study is to evaluated ChEE-SMEDDS for their physicochemical properties and in vivo using combination with doxorubicin to see blood serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitrit oxide (NO) activity and also cardio-hepato-histopathology of female Sprague Dawley rats. The results showed that ChEE-SMEDDS repaired cardio-hepato-histopathology profile of doxorubicin -induced rats, but did not reduce serum activity of NO, ALT and AST. These results indicated that ChEE-SMEDDS has potency to be developed and improved as cardio-hepato-protector agent in chemotherapy.Keywords: Citrus hystrix D.C., SMEDDS, Cardio-hepatoprotector, Histopathology, Chemoterap
Cytotoxic Effect of Jati Belanda Leaves towards Cancer Cell Lines
The initial research of Jati Belanda leaves extract (JBE) showed the inhibition of breast cancer cell growth (T47D). The phytochemistry screening showed that JBE contain flavonoid, alkaloid, polifenol, and volatile oil. The development of anticancer drugs need the molecular mechanism investigation in order to produce cancer-targeted drugs. The objective of this research is to determine the molecular mechanism of JBE cytotoxicity effect towards cancer cell lines. This research began with cytotoxicity asssay in vitro of JBE towards some cancer cell lines by MTT method. JBE was given in some variety of concentration. The result of this study showed that JBE do not contain tirosid, and contain flavonoid in the concentration of 0,976%. The result of cytotoxicity assay towards MCF-7, HeLa, T47D and Vero showed IC50 value 36,50; 58,02; 53,36; 1806,22 dan 2451,65 µg/mL respectively. It is concluded that JBE have a strong potency to inhibit the growth of WiDr cancer cell line.Keywords : jati belanda, T47D cells, cytotoxicit
Synergistic Effect of Arecoline in Combination with Doxorubicin on HeLa Cervical Cancer Cells
Arecoline, the main alcaloid of Areca cathecu L has been proven to posses cytotoxic activity against various cancer cell lines. The research conducted to examine the cytotoxic activity of arecoline alone and its combination with doxorubicin against HeLa cervical cancer cell line. Single treatment of arecoline in various concentration on HeLa cancer cell were done followed by the combinational treatment with doxorubicin. The cell viability as the parameter of cytotoxicity was measured using MTT (3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide) assay. The apoptotic effect was examined by double staining assay using etidium bromide–acridin orange. Arecoline did not show potent cytotoxicity effect against HeLa since the value of IC50 is 462 µM. The combinational treatment of arecoline and doxorubicin showed synergicity with the optimum CI value is 0,48 given by the treatment of 30mM arecoline combined with 125 nM doxorubicin. The result of this study shows that arecoline has potential to be proposed as co-chemotherapeutic agent for cervical cancer. However, further study on its molecular mechanism needs to be conducted. Keywords: cinnamon essential oil, doxorubicin, T47D cells, combination cytotoxicit
Anti-Inflammatory Effect of Ethanolic Extract of Curcuma aeruginosa Roxb Rhizome, Morinda Citrifolia Fruit and Apium graveolens Leaf on Lipopplysaccharide-induce RAW 264.7 Cell Lines
Curcuma aeruginosa Roxb., Morinda citrifolia and Apium graveolens are Indonesian plants which have been used in traditional medicine as an antihelmintic, antimicrobial, antiinflammation and antioxidant. In this study, the antiinflammatory activity of Curcuma aeruginosa Roxb. rhizome, Morinda citrifolia fruit and Apium graveolens leaf extract was investigated. All of extract was prepared by maceration with ethanol 70% and treated for antiinflammatory effect by using inducible-nitric oxide secretion measurement on lipopolysaccharide (LPS) - induce macrophage RAW 264.7 cells. We used three concentration of Curcuma aeruginosa Roxb. rhizome and Apium graveolens leaf extract at 25 ppm; 50 ppm; 100 ppm while for Morinda citrifolia fruit extract with 50 ppm; 100 ppm; 200 ppm. This study revealed that rhizome of Curcuma aeruginosa Roxb. and fruit of Morinda citrifolia extract inhibited inducible-nitric oxide synthesis with highest value of 84.2% at 25 ppm and 85,71% at 100 ppm in cells. However, leaf of Apium graveolens extract showed low inhibition with highest values of 18,85% at 100 ppm. This study demonstrates the potential of Curcuma aeruginosa Roxb. rhizome and Morinda citrifolia fruit as antiinflammatory agents.Keywords: Curcuma aeruginosa Roxb., Apium graveolens, Morinda citrifolia, antiinflammation, inducible-nitric oxide, lipopolysaccharide-induce macrophage RAW 264.7 cell
Brazilein Increased Cytotoxic Activity of Doxorubicin on MCF-7/DOX Cells
Brazilein is a compound obtained in a large amount from the dried heartwood of Secang (Caesalpinia sappan L.). Brazilein has strong cytotoxic effect in several cancer cell lines. This research was designed to evaluate the cytotoxic effect of brazilein and its combination with a chemotherapy agent, doxorubicin on MCF-7/DOX breast cancer cells. In the cytotoxicity assay, MCF-7/DOX cells were cultured in the presence of brazilein solely and in combination with doxorubicin for 24 hours and cell viability was evaluated by using MTT assay. MTT assay showed a dose-dependent inhibition of cell proliferation with IC50 value of 37 µM. Brazilein increased doxorubicin’s cytotoxic activity on MCF-7/DOX cells. Both of single treatment with different concentration of brazilein 12.5 and 25 mM or doxorubicin 0.8 and 1 mM gave cell viability percentage above 80%, but combination of them led to decrease the cell viability percentage significantly. Based on this research, it can be concluded that brazilein is potential to be developed as a co-chemotherapy agent on breast cancer cell that have been resistant to doxorubicin. Futher study must be held to evaluate its molecular mechanism.Keywords : brazilein, doxorubicin, MCF-7/DOX, cytotoxic.
Antituberculosis and Toxicity Assay of ethanolic extract of Mimba Cortex (Azadirachta indica JUSS.)
According to WHO has identified so much people with tuberculosis disorder, and includes a disease that causes death. Mycobacterium tuberculosis has been resistant to antituberculosis drugs were used, while the discovery of new synthetic antituberculosis are very slow. Traditionally, mimba cortex has been used to treat cough and bloody sputum. In previous research proved that the ethanol extract of mimba cortex can inhibit the in vitro growth of Mycobacterium tuberculosis. This study was conducted to determine the potential of mimba cortex as antituberculosis in vivo and toxicity test. Antituberculosis potency test in vivo in guinea pigs infected with Mycobacterium tuberculosis H37Rv directly into the bronchi using nebulizer. Then given mimba cortex extract 3 times a day 100 mg/kgBW and 50 mg/kgBW. Isoniazid, Rifampicin and Ethambutol used as a comparison. Antituberculosis assessment examination conducted by Mycobacterium tuberculosis on bronchial fluid speciments were taken every two weeks and tested in culture with Lowenstein-Jensen method. Acute toxicity test conducted on mice, the LD50 value calculation and observation of liver, kidney, and lung histopathology. The result of research showed that the ethanol extract of mimba cortex have antituberculosis activity in guinea pigs which has infected with Mycobacterium tuberculosis H37Rv, 3 times daily dosing of 100 mg/kgBW for 6 weeks, showed that bacterium from +3 to negative, and 3 times daily dosing of 50mg/kgBW showed that bacterium from +3 to +1. Acute toxicity test results showed LD50 11.85 ± 0.571. That is including mild toxic category.Keywords: mimba cortex, antituberculosis activity, acute toxicit
Analysis of the Histopathology, TNF-α of Microglia Cells Expression, NRG-1/erbB Oligodendrocyte, and Ki67/Apoptosis of Dentate Gyrus Rattus novergicus Brain After Acute Traumatic Brain Injury
Head trauma or traumatic brain injury (TBI) gives most serious impact on the central nervous system. Several experimental models have been established to mimic different pathogenesis characteristics of TBI. The purpose of this study was to determine whether there is evidence of hystopathological lesions in the brain tissue after Marmorou TBI models. This study uses Rattus norvegicus Sprague Dawley strain. Macroscopic and microscopic observations on the brain tissue were done. Macroscopic lesions were observed in the brain. Microscopic observation was performed with Haematoxylin-Eosin (HE) staining and immunohistochemistry on the distribution of microglia cells and pyramidal cells in the cortex. Meanwhile, the distribution of NRG-1/ErbB, proliferation, and apoptosis were observed in the hippocampus. The results of macroscopic observation showed that there were wounds caused by falling loads and vasodilatation. On microscopic observation, the TBI group showed an increase in neutrophils distribution and distribution of activated microglia to produce TNF-α, and decrease in the number of cortical pyramidal cells significantly. The distribution of NRG-1 tended to decrease after exposure of TBI and had no effect on its receptor, erbB. Exposure of TBI appears to lower the activity of neuronal cells proliferation in dentate gyrus (DG) area and significantly increase the number of apoptotic cells. Marmarou model is a physiological model of TBI that spontaneously occurs following a trauma to the head, for example trauma due to an accident. This data can be used as a preliminary data of inflammation and tissue regeneration of disrupted adult brain. Therefore, this research could be used as the basis in the studies of therapeutic agents in the process of neurogenesis of brain cells.Keywords: traumatic brain injury, ERG-1/ErbB, dentate gyrus, Ki67, TNF-a, microgli