Indonesian Journal of Cancer Chemoprevention
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Pentagamaboronon-0-Sorbitol Induces Apoptosis through Elevation of Reactive Oxygen Species in Triple Negative Breast Cancer Cells
Full text linkBreast cancer is the most common type of cancer causing mortality for women due to metastasis. More than 50% of breast cancer patients are suffered lung metastases. One strategy to target the cancerous cell is Boron Neutron Captured Therapy (BNCT) which showed high affinity toward cancer cells and reported to have anti-proliferative as well as anti-metastatic activities. Pentagamaboronon-0 (PGB-0) is a curcumin analogue substance which had reported to exert anticancer activities against Her-2 expressing as well as triple negative breast cancer cells. Despite its great potency as BNCT agent candidate, this compound also exerted several anticancer properties. Complex formation of this substance with sorbitol was achieved to improve the solubility and maximize compound’s delivery to the target cells. This study aimed to investigate the ability of Pentagamaboronon-0-Sorbitol (PGB-0-So) to modulate cell cycle and induce apoptosis especially through the mechanisms of reactive oxygen species (ROS) modulation. The 3-(4,5-dimethylthiazzol-2yl)-2,5-diphenyltetrazolium (MTT) cytotoxicity assay of PGB-0-So against 4T1 breast cancer cell line were found to exert potential effect in dose-dependent manner with lethal concentration (IC50) values of 39 μM. The cytotoxicity of PGB-0-So complex was found to be increased considerably compared with that of PGB-0. Cell cycle modulation identified using propidium iodide (PI) staining showed cell accumulation in S phase following treatment with PGB-0-So. Apoptosis induction assay analyzed using flowcytometer with Annexin V and PI staining on its IC50 dose was found to induce programmed cell death (apoptosis). The sub-IC50 treatment of this compound was also improved the cellular ROS level which also took role in apoptosis induction. These findings suggest that PGB-0-So is potential as an anticancer agent.Keywords: Curcumin analogue, PGB-0-So, Anticancer, 4T1 cell line, ROS modulation
Molecular Docking Study of Mangosteen (Garcinia mangostana L.) Xanthone-Derived Isolates as Anti Androgen
Full text linkAndrogen receptor (AR) is the member of steroid hormone receptor involved in the progression of prostate cancer growth due to receptor over-activation. On the other hand, mangosteen (Garcinia mangostana L.) as a medicinal plant contains xanthone-derived compounds which were known to have cytotoxic activity towards any types of human cancer cells. This research aims to determine xanthone-derived isolates potency from mangosteen as AR antagonists. The study was carried out through molecular docking assay utilizing AutoDock 4.2.6 using androgen receptor obtained from PDB ID 2AM9, testosterone as native ligand, and bicalutamide, flutamide, and nilutamide as reference. The results indicated that three isolates (1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone, mangostinone, and trapezifolixanthone) have the highest potency to be AR antagonist seen from the lower bond-free energy value than all of reference ligand. The lowest bond-free energy was provided by mangostinone with a ΔG value of -10.05 kcal/mol. However, the highest difference of residual amino acids interaction with testosterone and similar interaction with bicalutamide was provided by 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone, with five different amino acids with testosterone and nine similar amino acids with bicalutamide, respectively. Interestingly, 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)xanthone has similar hydrogen bond with the key residue amino acids of AR (705-Asn and 711-Gln) which indicates probably partial agonist activity while mangostinone has the highest amount of hydrogen bond in the absence of hydrogen bond towards key residual amino acids of AR. The results concluded that three specific derived-xanthone compounds were predicted to have activity as AR antagonists.Keywords: Prostate cancer, Androgen receptor, Mangosteen, Xanthone, Molecular docking
Human Platelet Lysate (HPL) as an Alternative Media Propagation of T47D Cells Line
Full text linkFetal bovine serum (FBS) is a gold standard as a supplement to cell and tissue culture media. This is due to a large number of Growth Factor (GF) contained in FBS. However, the use of FBS is at risk of transferring endotoxins, prions, bacteria and viruses from animals to humans, so it is risky to be used on cell therapy. Human Platelet Lysate (HPL) is a medium that can be developed as an alternative cell growth medium. The advantage of HPL is that it does not contain aggregate platelets so it does not cause the cells to clot. This condition causes HPL to be used as a substitute medium replacing FBS for cell propagation. The use of HPL for cell propagation has been widely reported. However, the use of HPL in cancer cells has not been found. Thus, this study aims to see the effectiveness of HPL as a T47D cell culture medium. The study began with donor selection with criteria for the male sex, the blood type O, the age ≤35 years. Furthermore, the Platelet Concentrate (PC) was processed into HPL then measured pH, total protein and albumin levels. The cell viability was measured using the MTT assay to determine the ability of cell proliferation when propagation using HPL. The doubling time test was carried out as in the cell proliferation test. However, the incubation was carried out for 24 h, 48 h and 72 h and the HPL concentration used was 5%. The result shows that HPL 10% and 20% ability to increase proliferation better than the FBS 10%. HPL with a 5% concentration ability to shortens the doubling time than FBS 10% (doubling time is less than 19.94 h). It this study, cell proliferation is influenced by the pH of HPL and total protein but not by the amount albumin.Keywords: Human Platelet Lysate, Proliferation, T47D cell line, total protein, albumin
Analgesic, Anti-Inflammatory and Anti-Biofilm-Forming Activity of Potato (Solanum tuberosum L.) Peel Extract
Full text linkThe utilization of natural resources, one of which is plants, has been researched as an alternative to synthetic drugs because of their natural content. Potato (Solanum tuberosum L.) peels, the parts of potatoes that are often cut off and discarded, have been reported to have some phenolic compounds and flavonoids in their composition. The extract of potato peels was investigated for its analgesic, anti-inflammatory, and anti-biofilm-forming properties. A hot plate test was conducted to assess the analgesic activity in treatment doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg with paracetamol as the reference drug and distilled water as the negative control, while carrageenan-induced paw edema was used to assess anti-inflammatory activity in treatment doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg with diclofenac as the reference drug and distilled water as the negative control. Anti-biofilm-forming activity was tested by using the crystal violet assay. The results showed that, compared with the negative control, treatment doses of 100 mg/kg and 200 mg/kg significantly (p < 0.05) reduced pain stimuli, whereas a treatment dose of 100 mg/kg, 200 mg/kg, and 400 mg/kg significantly (p < 0.05) reduced the edema volume increment. However, compared with the positive control, paracetamol and diclofenac were associated with the least pain stimulus and the least edema volume increment, respectively. Potato peel extract against S. mutans biofilm formation demonstrated effectiveness (p < 0.05). Based on these data, it can be concluded that potato peel extract has analgesic, anti-inflammatory, and anti-biofilm-forming activities, as demonstrated in this study
Activity of Noni Fruit (Morinda citrifolia L.) Ethanolic Extract on Class mu Glutation S-Transferase of Lung Rat
Full text linkOne of the main modalities of cancer treatment is chemotherapy, which uses chemicals that are generally electrophilic. These xenobiotic compounds sometimes does not produce effective response due to activity of glutathione S-transferase (GST) which inactivate the xenobiotics. Several natural phenolic compounds were reported to inhibit GST activity in vitro. Noni fruit (Morinda citrifolia L.) which contains flavonoids and other phenolic compounds such as scopoletin and morindon is proposed to interfere GST activity. This study aimed to analyze the effect of ethanolic extract of Noni fruit in vivo on GST activity in lung rat using 1,2-dichloro-4-nitrobenzene (DCNB). This substrate is a specific for class mu GST. First, rats were administered with ethanolic extract of Noni and dimethylbenz(α)anthracene (DMBA) for two weeks. The cytosolic fraction of lung was isolated then the GST activity was determined by simple kinetic program which was automatically calculated using spectrophotometer. The results showed that ethanolic extract of Noni in 1 and 5% (w/v) of concentration induced class mu GST activity, whereas 10% (w/v) of concentration inhibited class mu GST activity. After a treatment with DMBA, all tested concentrations of ethanolic extract of Noni inhibited class mu GST activity of lung rat significantly. These results indicated that Noni fruit extract can be further developed as a supportive agent of a chemotherapy drug.Keywords: DMBA, GST, Morinda citrifolia L., spectrophotometer
Nanoparticle from Medinilla speciosa with Various of Encapsulating Agent and Their Antioxidant Activities Using Ferric Reducing Assay
Full text linkAntioxidants are agents that can reduce free radicals. Parijoto fruit (Medinilla speciosa) contains flavonoids that could act as an antioxidant. However, those flavonoids are water-soluble and show low bioavailability. Nanotechnology is a potential approach to improve the bioavailability of flavonoids from Parijoto fruit. This study was conducted to determine the antioxidant activity of parijoto nanoparticles with variations of the chitosan, alginate, and chitosan/alginate encapsulants. Secondary metabolites of parijoto fruit were using the maceration method. The synthesis of parijoto nanoparticles was conducted using the ionic gelation method with chitosan, alginate, and chitosan/alginate encapsulation. Parijoto nanoparticle size and distribution were characterized using Particle Size Analyzer (PSA). The formation of nanoparticles in colloids was determined as a percent. The antioxidant activity of nanoparticle was evaluated using Ferric Reducing Antioxidant Power (FRAP) method using a UV-Vis spectrophotometer. Chitosan encapsulation produced nanoparticles with a size of 269.3 nm, pdI 0.372 and transmittance 99.379%. Alginate encapsulation produced a particle size of 366.4 nm, pdI 0.589 and transmittance 99.690%. The combination of chitosan/alginate encapsulants produced a particle size of 187.00 nm, pdI 0.239 and transmittance 99.894%. Parijoto nanoparticles obtained from chitosan, alginate, and chitosan/alginate encapsulant showed strong antioxidant powers indicated by IC50 values 2.442±0.047 ppm, 3.175±0.169 ppm and 2.115±0.045 ppm, respectively. Altogether, our study shows that parijoto nanoparticles are potent as antioxidant agents.Keywords: Alginate, antioxidant, chitosan, FRAP, Medinilla speciosa, nanoparticl
Fingerroot (Boesenbergia pandurata) Extract Inhibits Proliferation and Migration of 4T1 Metastatic Breast Cancer Cells
Full text linkFingerroot (Boesenbergia pandurata) is an Indonesian herb, with anti-proliferation and anti-migratory effects against several cancer cells. This study aims to investigate the anticancer property of Fingerroot Extract (FE) in combination with doxorubicin (Dox) against 4T1, a metastatic breast cancer cell lines. FE was prepared by 96% ethanol maceration and characterized by thin-layer chromatography analysis. FE was subjected to a cytotoxicity test with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay alone or in combination with 10 nM Dox against 4T1 cells. Cytotoxic effect was then confirmed by measure reactive oxygen species (ROS) intracellular level using 2’,7’-dichloroflourescin diacetate (DCFDA)-staining flow cytometry-based assay. The anti-migratory effect was observed using scratch wound healing assay and gelatin zymography to investigate matrix metalloproteinase (MMP)-9 expression. FE showed a cytotoxic effect with an inhibitory concentration 50 (IC50) value of 25.5±3.9 μg/mL and performed an improved effect in combination with 10 nM Dox. A single treatment of FE decreased ROS intracellular level, while in combination with Dox, FE increased the ROS intracellular level. Further, at 42 h observation, FE and its combination with Dox inhibited the migration of 4T1 cells with % closure of 82.6 and 82.5, respectively, correlates with a significant decrease of MMP-9 expression. Overall, FE performs a cytotoxic activity and anti-migration activity on 4T1 breast cancer cells.Keywords: Boesenbergia pandurata, cytotoxic, ROS, anti-migration, 4T1
Synergistic Cytotoxicity Effect by Combination of Methanol Extract of Parijoto Fruit (Medinilla speciosa Reinw. ex. Bl) and Cisplatin Against Hela Cell Line
Full text linkAs one of the leading causes of death in worldwide, cervical cancer requires the effective therapies to reduce its mortality rate. One of the chemotherapy agents that frequently used in the treatment is cisplatin. However, due to drug resistance and its side effects, an agent that can be combined with cisplatin is needed. Parijoto fruit (Medinilla speciosa Reinw.ex.Bl) contains secondary metabolites compounds that have potential as anticancer. The study aims to determine the cytotoxic effect of methanol extract of Parijoto fruit calculated from the IC50 value and the synergicity of the combinational treatment with cisplatin evaluated from the Combination Index (CI) value and its cell viability by using MTT assay. Results showed that methanol extract of Parijoto fruit (MEP) performed cytotoxic effect on HeLa cell line with IC50 of 209.6 μg/mL while the value of IC50 of cisplatin against HeLa cells amounted to 12.8 μg/mL. The combination of 26.205 ppm (1/8 IC50) of MEP and 1.601 ppm (1/8 IC50) of Cisplatin performed synergistic effect on HeLa cell line with the CI value of 0.69. From the above results, it can be concluded that MEP is potential as co-chemotherapy agent based on the synergistic cytotoxicity effect with cisplatin.Keyword: cytotoxic, Medinilla speciosa, cisplatin, co-chemotherapy, MT
Ethanolic Extract of Citrus reticulata Peel Inhibits the Migration of WiDr Colon Cancer Cells
Full text linkColorectal cancer is third rank on the cancer cases in Indonesia. To cure the cancer needs big cost and lot of effort. On the other side, the side effect of medicine or chemotherapy on patient need to reduce. Cancer cell spread to other tissue based on its migration and invasion ability. Citrus reticulata peel contains flavonoid such as Tangeretin and Nobiletin, both of this compounds have anticancer activity. The aims of this study is to reveals the potency of ethanol extract of Citrus reticulata peel on the inhibition of migration on WiDr colon cancer cells. The toxicity of ethanol extract of Citurs reticulata peel on WiDr colon cancer line was measured using 3-(4,5-dimethyltiazol-2-il)-2,5-diphenyltrazolium bromide (MTT) assay and investigate the cell migration was using scratch wound healing assay. The ethanol extract of Citrus reticulata peel showed the value of inhibitory concentration 50 (IC50) was 184.5 μg/mL, this result categorize as moderate cytotoxic. Meanwhile the migration assay showed that the deceleration of migration occurred on 0.5 IC50, 0.33 IC50 and 0.25 IC50 during 24 h and 36 h incubation, event thought there were not significant different (p>0.05). The ethanol extract of Citrus reticulata peel has a potential migration inhibition on WiDr cell line.Keywords: Citrus reticulata, WiDr cell line, migratio
The Role of Hypoxic Mesenchymal Stem Cells Conditioned Medium in Increasing Vascular Endothelial Growth Factors (VEGF) Levels and Collagen Synthesis to Accelerate Wound Healing
Full text linkFull-thickness wound are areas damage of skin associated with loss of epidermis and dermis. The wound healing mechanism consists proliferation, migration and remodeling. Hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM) contains lots of soluble molecules, such as protein growth factor and cytokine anti-inflammation. The soluble molecule of HMSCs-CM plays a critical role in wound healing by upregulation of VEGF and collagen synthesis. The objective of this study was to evaluate the effect of HMSCs-CM on VEGF and collagen concentrations in rats with incised wounds. The methods of this study were an experimental animal study with post-test only control group design was performed involving 24 Wistar rats. The rats were randomized into four groups consisting of sham, control and two treatment groups (gel of HMSCs-CM at doses of 200 μL and 400 μL). The VEGF levels and collagen density were analyses using ELISA assay and Masson-trichome specific staining, respectively. One-way ANOVA and Post Hoc LSD were used to analyses the data. The results of this study showed that a VEGF levels was significant increased on day 6 with doses-dependent manner. Interestingly, the VEGF levels gradual decrease on day 9. In addition, the decreased of VEGF levels on day 9 in this study in line with our findings in which we found there was a trend in the decreased of collagen density, it indicated the completion of remodeling phase and there has been an acceleration in wound healing. This study demonstrated that HMSCs-CM were able to regulate VEGF levels and collagen synthesis in accelerate wound healing. The role of HMSCs-CM stimulate cutaneous wound healing should be clarified further.Keywords: hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM), vascular endothelial growth factor, collagen synthesis, paracrine factor