Indonesian Journal of Cancer Chemoprevention
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Antigenotoxicity Activity of Papaya (Carica papaya L.) Leaf Ethanolic Extract on Swiss Mice Induced Cyclophosphamide through Mammalian In Vivo Micronucleus Test
Get PDFCyclophosphamide (CPA) is an effective chemotherapeutic agent, but has side effect, causing DNA damage (genotoxic). Papaya leaf (Carica papaya L.) is known has flavonoid compound, quercetin. Quercetin is known has DNA protecting effect (antigenotoxic effect) by metabolism modulation. Thus, the aim of this research is to investigate the antigenotoxic effect of ethanolic extract of papaya (Carica papaya L.) leaf (EEPL) on CPA induced mice. The antigenotoxic effect was evaluated by mammalian in vivo micronucleus test. EEPL was orally administered as single treatment at dose 1000 mg/kgBW and in combination with CPA 50 mg/kgBW at dose 250 mg/kgBW; 500 mg/kgBW; and 1000 mg/kgBW. Molecular docking using PLANTS on CYP 3A4 was performed to explore the antigenotoxic effect mechanism. The three different combination dose of EEPL with CPA significantly (P<0.05) decreased the amount of micronucleated polychromatic erytrhocyte (MNPCE)/1000 polychromatic erythrocyte (PCE) and also increased % PCE/(PCE+normochromatic erythrocyte (NCE)), compared with single dose of CPA. Nevertheless, the antigenotoxic effect wasn’t significant compared with each combination dose. The docking score result showed quercetin (-82,41) has more potent interaction to CYP 3A4 than cyclophosphamide (-70,16) and both of them has similar active site at amino acid residue Ile 369 and Thr 309. The results obtained indicated that EEPL at dose 250 mg/KgBB is the optimal dose as antigenotoxic agent by interaction between quercetin with CYP 3A4 based on molecular docking.Keywords: antigenotoxic, Carica papaya L., MNPCE, in viv
Ethanolic Extract of Hedyotis corymbosa and Its Combination with 5-FU Inhibit Cyclin D Expression on WiDr Colorectal Cancer Cell
Get PDFHedyotis corymbosa has been used for long time as an important component in several folklore medicine formula to clinically treat various types of cancer, including colorectal cancer (CRC). Previously, Hedyotis corymbosa ethanolic extract (HEE) which contain ursolic acid reported to inhibit CRC growth via induction of cancer cell apoptosis and blocked the cell cycle, preventing G1 to S progression where cyclin D highly espressed in this phase. 5-fluorouracil (5FU), the first line chemotherapy of colorectal cancer have had resistence and possessed several side effects such as neutropenia, immunosuppression, diarrhea, and also constipation. Therefore, the aim of this research is to conduct the antiproliferative effect and molecular analysis of HEE and its combination with 5FU. Molecular docking study was also done to approach the specific protein target of the compound. Antiproliferative effect was conducted by MTT assay, while cyclin D expression was examined by immunofluorescence. The proliferative effect showed that both HEE and 5-FU had cytotoxic effect with IC50 value of 65 µg/mL and 90 µM respectively, meanwhile the combination of HEE and 5FU have synergism effect with CI = 0.48 on dose HEE = 22 µg/mL and 5FU= 6.25 µM. Immunofluorescence assay showed HEE and its combination with 5FU suppressed the expression of cyclin D. From molecular docking simulation, ursolic acid performed stable interaction with cyclin D. Our findings suggest that HEE may be an effective treatment for co-chemotherapic for 5-FU through inhibition of cyclin D expression.Keywords : Hedyotis corymbosa, 5-fluorouracil, colorectal cancer, WiDr, cyclin D
Immunostimulant Effect of Garlic Chives Leaf Ethanolic Extract (Allium tuberosum) by Increasing Level of Antioxidant at Rats Doxorubicin-Induced Rats
Get PDFCancer is one of the leading causes of death in the world, approximately 14 million new cases and 8.2 million deaths each year. Doxorubicin is a well-known chemotherapy drug which frequently used in treating various types of cancer. However, doxorubicin posesses several side effects including cardiotoxic, hepatotoxic, nephrotoxic, and immunosuppression. One of the natural product that can be used as an adjuvant of doxorubicin to reduce the toxic effects is garlic chives (Allium tuberosum). The purpose of this study was to determine the effect of Allium tuberosum based on hematological profile, levels of CD4+, CD8+, and MDA serum of male Wistar rats which induced by doxorubicin. The hematological profile was analyzes by blood smear, levels of CD4+ and CD8+ were conducted by flowcytometry and levels of MDA serum were determined by spectrofotometry. The results showed that the etanolic extract of Allium tuberosum (EAT) increased neutrophil and lymphocyte, percentage of CD4+ cells (p<0.01) and CD8+ cells. It also decreased the levels of serum MDA (p<0.01). These results indicated that EAT work as immunostimulant possibly through an antioxidant mechanism (MDA). It can be concluded that EAT can be developed as adjuvant for doxorubicin.Keywords: doxorubicin, Allium tuberosum, immunostimulant, antioxidant, CD4+, CD8+
Anti-Aging Activity Of Cucurbita moschata Ethanolic Extract Towards NIH3T3 Fibroblast Cells Induced By Doxorubicin
Get PDFDegenerative disease caused by decreasing organ function in old people has become the biggest death cause in the world. This aging process marked by senescence activity. An anti-aging agent from the medicinal plant has high potency to be developed, such as pumpkin seed (Cucurbita moschata) which contain tocopherol as antioxidant. The aim of this study is to investigate the anti-aging effect of pumpkin seed extract (PSE) on NIH 3T3 fibroblast normal cell induced by doxorubicin. This anti-aging effect was observed using MTT assay continued by SA- βgal (Senescence-Associated Beta-Galactosidase) activity detection test. The stability of molecular interaction between tocopherol and doxorubicin to CYP 3A4 as the oxidase enzyme was conducted using molecular docking. Based on in vitro test, PSE is not cytotoxic to NIH 3T3. PSE at the dose of 100,200,400, and 800 μg/mL decreased % cell senescence by 2,77; 4,5; 6; and 18 times respectively. Meanwhile, in silico test indicated that tocopherol (-107,409) has a higher interaction to CYP 3A4 compared to doxorubicin (-70,52). Both compounds have a similar binding site in Leu 364; Phe 435; Pro 434; Cys 442; Ile 369; Thr 309; dan Ala 305. The overall result of this study showed that PSE has anti-aging effect by decreasing SA- βgal activity. This anti-aging activity possibly due to the interaction between tocopherol to CYP 3A4 based on molecular docking.Keywords: anti-aging, Cucurbita moschata, tocopherol, SA-βgal, molecular dockin
The Effect of Marigold Leaves and Doxorubicin Toward Cell Cycle and Apoptosis of T47D Cells
Get PDFDoxorubicin is a commonly used chemotherapeutic agent in patients with breast cancer. The risk of side effect using of doxorubicin such as cardiomyopathy and congestive heart failure which can lead to death. One of the approach to overcome overloaded use of doxorubicin is the combined use with a chemopreventive agent (cochemotherapy), including the leaf extract of marigolds (Cosmos caudatus Kunth.). This research aims to reviewing the effect of the methanol extract of leaves of marigolds on the cytotoxic activity of doxorubicin in modulating cell cycle and apoptosis of breast cancer cells T47D. Determination of the cytotoxic activity of methanol extract of leaves of marigolds and doxorubicin as well as a combination of both conducted by MTT assay. modulation surveillance of cell cycle and apoptosis induction is done by using flowcytometry and analyzed by FACS Calibur program. Cytotoxicity assay single treatment of the methanol extract of leaves of marigolds produce use values of IC50 504,840 μg/ml, whereas IC50 values doxorubicin is 141,055 nM. The synergistic effect was shown a combination of methanol extract leaves marigolds and doxorubicin at concentrations of 84,17 μg/ml -23,5 nM; 84,17 μg/ml -47 nM; 126,25 μg/ml -23,5 nM; 252,5 μg/ml -35,25 nM and 252,5 μg/ml -71 nM with a combination index value (CI) consecutively of 0,5; 0,6; 0,6; 0,6 and 0,6. Observations modulation of cell cycle and apoptosis induction combination of methanol extract leaves marigolds and doxorubicin at concentrations of 84,17 μg/ml -23,5 nM, said that a combination of the methanol extract of leaves of marigolds and doxorubicin to inhibit the proliferation of cells in G2 / M phase and able to induce apoptosis of breast cancer cells T47D.Keywords: methanol extract of leaves of marigolds, doxorubicin, flowcytometry, cell cycle, apoptosis
Antiproliferative Effect of Secang Heartwood Ethanolic Extract (Caesalpinia sappan L.) on HER2-Positive Breast Cancer Cells
Get PDFHuman Epidermal Growth Factor Receptor 2 (HER2) plays critical role in the initiation of breast cancer cell proliferation. Inhibition of HER2 overexpression is a promising strategy in the treatment of breast cancer. One of the potential natural substances that possess cytotoxic in cancer cells is Secang (Caesalpinia sappan L.). Ethanolic extract of secang heartwood containing brazilein and brazilin shows cytotoxic effect on various cancer cells. Thus this research aims to determine the proliferative inhibition activity of secang heartwood ethanolic extract (SEE) through HER2 expression on MCF-7/HER2 positive. Cytotoxic activity of SEE on MCF-7/HER2 positive cells was observed by MTT assay, meanwhile the inhibition activity of HER2 on MCF-7/HER2 cells was determined by immunofluoresence assay. Furthermore, to confirm the possible mechanism of brazilein and brazilin for its cytotoxic activity was studied through molecular docking using PLANTS software. Based on this study, SEE exhibited cytotoxic effect on MCF-7/HER2 positive cells with IC50 value of 25 µg/ml, and EES also inhibited HER2 expression, indicated that the antiproliferative effect of SEE was possible through the inhibition of HER2. Docking score of brazilein, brazilin, and native ligand on HER2 were -77; -73; -120 respectively, showed the affinity of brazilein in HER2 was lower than affinity of native ligand, but they had specific amino acid to interaction. Hence, SEE can be developed as one of promising chemopreventive agent from natural products.Keywords: Caesalpinia sappan L., cytotoxic, immunofluorescence, molecular docking, MCF7/HER2 cell
Essential Oil of Javanese Turmeric (Curcuma xanthorrhiza, Roxb) Decrease Level of LDL-Cholesterol and Body Weight In Rats
Get PDFThe aim of the present study was to investigate the effect of the essential oil of Javanese turmeric (Curcuma xanthorrhiza, Roxb) on level of low density lipoprotein-cholesterol (LDL-C) and body weight in rats. The groups were induced by high fat diet for 30 days to produce hyperlipidemia. The rats were treated with essential oil 25 mg/kgBW and simvastatin 25 kg/kgBW for 30 days. The LDL-C and body weight were measured on day one before treatment, and on day thirthy of the treatment. The results showed that the essential oil decreased the level of LDL-C and body weight in rats.Keywords: Javanese turmeric, Curcuma xanthorrhiza, essential oil, lipoprotein, simvastati
Jure Leaf Extract (Nerium indium Mill.) Increased 5-Fluorouracil Sensitivity through Inhibition of NF-κB Activation and Transporter Protein in WiDr Colon Cancer Cell
Get PDF5-Fluorouracil (5-FU) is the first line chemotherapeutic agents for colon cancer therapy. Long term used of 5-FU caused cancer cell resistency. Thus, co-chemoteraputics agent should be developed to increase cells sensitivty towards 5-FU. Jure leaf (Nerium indicum Mill) extract (JLE) contains oleandrin which has cytotoxic effect on colon cancer cell. The ain of this study was to investigated the mechanism of JLE to sensitized colon cancer cell toward 5-FU through NF-κB inhibition and MRP protein repression. JLE was extracted by soxhletation method. Based on molecular docking to MRP protein, docking score of oleandrin (-50,496) was higher than native ligand ATP (-125,817). Oleandrin could interfere interaction with MRP. JLE increased 5-FU sensitivity a dose of 2 µg/mL JLE dan 12,5 µM 5-FU with the combination index (CI) of 0,594. Combination of JLE and 5-FU also inhibit p65 protein expression on WiDr cell.Keywords: cytotoxic, Nerium indicum Mill., oleandrin, immunofluorescence, molecular dockin
Heartwood of Secang (CAESALPINIA SAPPAN L.) Ethanolic Extract Show Selective Cytotoxic Activities on T47D and Widr Cells But Not on Hela Cells
Get PDFThe present study investigate the selectivity of heartwood of secang ethanolic extract (SEE) on T47D breast cancer cells, WiDr colon cancer cells, and HeLa cervical cancer cells, compared to Vero normal epithelial cells. The cytotoxic effect was evaluated by using MTT assay with 24-hour treatment to get IC50values. Selectivity was evaluated by using selectivity index (SI). SEE had a potent cytotoxic activity on T47D and WiDr cancer cells (IC50 3), while in HeLa cells is not selective (SI < 3). This result indicating its potential of Caesalpinia sappan as a chemopreventive agent in cancer therapy.Keywords: Cancer, selectivity, Secang, T47D, WiDr, HeLa, Ver
The Effect of Co-Administration of Telang Leaves Ethanolic Extract Towards Fluoxetin’s Sedative Effect on Male Balb/C Mice Based on Sleeping Duration Parameter
Get PDFOne of Telang plant’s advantages is its activity as sedative agent. Previous studies indicate that Telang plant has anticonvulsant activity on mice at certain dose. This study was conducted to find out the sedative effect of Telang plant, particularly its leaf, when being co-administered with fluoxetin. Phytochemical analysis was carried out qualitatively on Telang ethanolic extract leaves (TEE) to find out the content of chemical compound first.This study was an experimental research with post-test only control group design, employing male balb/c mice. The effect of Telang ethanolic extract co-administration with fluoxetin was observed. The parameter being used in the study was the duration of sleep. Analysis was done by comparing mice sleeping duration prior to administration of fluoxetin alone and in combination with Telang ethanolic extract. The data was then analyzed using SPSS 17.0 for Windows.The results showed that TEE contained tannin, saponin, and flavonoid compounds, and co-administration of TEE and fluoxetin at various doses could provide sedative effect on mice. The co-administration of 400 mg/kgBW extract and 15 mg/kgBW fluoxetin could provide the mean sleeping duration 43 minutes longer than positive control.Keywords: telang leaves ethanol extract, fluoxetin, sleeping duratio