Indonesian Journal of Cancer Chemoprevention
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Pentagamaboronon-0 Fructose Inhibited Migration and Overexpression of Matrix Metalloproteinases 9 on MCF-7/HER2 Breast Cancer Cells
Full text linkThe incidence of Breast Cancer Metastasis (MBC) can be categorized in stage IV as well as being the leading cause of death in cases of breast cancer. MBC prognosis is known to be weak, frequent recurrent, and MBC patients have only a survival rate of about 5 years. One of the proteins that causes breast cancer metastasis is Human Epidermal Growth Factor 2 (HER2). Pentagamaboron-0 (PGB-0), a newly curcumin analogue performed cytotoxic effect on HER2-positive breast cancer cells but it is practically water-insoluble. The aims of this study are to determine anti-metastatic activity of a more soluble form of PGB-0 namely PGB-0 fructose complex (PGB-0-F) toward HER2 positive cancer (MCF-7/HER2) cells. PGB-0-F was obtained from Cancer Chemoprevention Research Centre Faculty of Pharmacy Universitas Gadjah Mada. Based on scratch wound healing assay result, PGB-0-F inhibited cell migration especially in combination with doxorubicin at the concentration 15 μM. Under gelatin zymography assay, PGB-0-F in combination with doxorubicin decreased Matrix Metalloproteinases 9 (MMP-9) expression compare to the doxorubicin. Hence, PGB-0-F has a potency to be developed as anti-metastatic agent on HER2 overexpression breast cancer.Keywords : HER2, MCF-7/HER2, PGB-0-F, Metastasi
RANKL and TNF-α-induced JNK/SAPK Osteoclastogenic Signaling Pathway was Inhibited by Caffeic Acid in RAW-D Cells
Full text linkCaffeic acid, a natural substance found majorly in fruits, grains, and herbs, is known to have therapeutic benefits. One of which is to inhibit bone resorption by targeting osteoclastogenesis through inhibition of the Cathepsin K, p38 Mitogenactivated Protein Kinase (MAPK), Nuclear Factor of Activated T-cells c1 (NFATc1) and Nuclear Factor kB (NFkB). Besides p38 MAPK, the c-Jun N-terminal kinase (JNK)/stressactivated protein kinases (SAPK), another member of MAPK family, has been reported to play important roles in osteoclastogenesis. Hence, current study was undertaken in order to investigate mechanism of Caffeic Acid towards JNK/SAPK pathway. Tartrate Resistant Acid Phosphatase (TRAP) staining was performed on caffeic acid-treated and RANKL-TNFα-induced RAW-D cells. Western blot analysis was performed to detect JNK/SAPK and phosphorylated-JNK/SAPK. Protein bands were quantified and statistically analyzed. Treatment of 10 μg/mL Caffeic Acid inhibited 20 ng/mL RANKL and 1 ng/mL TNFα-induced RAW-D differentiation into TRAP+ osteoclast-like polynuclear cells. Induction of 20 ng/mL of RANKL and 1 ng/mL of TNFa for 0.2 or 1 hour, significantly increase phosphorylation of JNK/SAPK as compared with control. Treatment of 10 μg/mL Caffeic Acid significantly inhibited the 20 ng/mL of RANKL and 1 ng/mL of TNFa-induced phosphorylation of JNK/SAPK. Taken together, Caffeic Acid could inhibit the RANKL and TNFa-induced osteoclastogenesis through JNK/SAPK.Keywords : Caffeic Acid, RANKL, TNF, RAW-D cells, osteoclastogenesis, JNK, SAP
A Review: The Emerging Nutraceutical Potential of Pumpkin Seeds
Full text linkThe pumpkin belongs to the family of Cucurbitaceae, is a well-known edible plant that has been frequently used as functional food or herbal medicine. Pumpkins contain rich unsaturated fatty acids, phytoestrogens and vitamins E in their seeds that have potential pharmaceutical, nutraceutical, and cosmeceutical properties. Information regarding their nutritional components and therapeutic properties of pumpkin seeds has expanded dynamically in the recent years and this review focus on the three main components of pumpkin seeds that described before. Several types of unsaturated fatty acids are the dominant component in pumpkin seeds which can play a role in the disease prevention and promote health. Pumpkin seeds also contain the important phytoestrogen compounds, i.e., secoisolariciresinol and lariciresinol that have estrogenic-like effect such as preventing hyperlipidemia and osteoporosis for menopausal women. Phytoestrogens in pumpkin seeds also could be related to a reduced hormone-dependent tumor. Pumpkin seeds are rich in vitamin E contents as an emerging free radical scavenger, anti-aging and antioxidant such as a-tocopherol and g-tocopherol. Findings of these studies prove that patents field for the innovation product of pumpkin seeds holds promise for the future along with their immense nutraceutical properties.Keywords : pumpkin seeds, estrogenic, anticancer, antioxidant, nutraceutica
Ethanolic Extract of Hedyotis corymbosa L. Inhibits Migration and MMP-9 Activity on Metastatic Breast Cancer Cells
Full text linkMany natural products have been widely explored for their pharmacological activities, including anticancer activity. Hedyotis corymbosa L. is known for its anticancer properties toward several cancer cell lines. The study aims to investigate whether ethanolic extract of Hedyotis corymbosa L. (EEH) performs anticancer properties by inhibiting migration and metastasis on breast cancer cells. Cytotoxic evaluation by using MTT assay was carried out to determine EEH effect on 4T1 breast cancer cells, meanwhile to investigate the treatment of EEH in migration and metastasis inhibitory effect, scratch wound healing assay and gelatin zymography were conducted in this study. The data showed that EEH possessed cytotoxic activity with IC50 value of 400 μg/mL. Interestingly, migration inhibitory effect was shown up to 42 hours and the activity of MMP-9 was also decreased after the treatment with EEH. According to these findings, we suggest that Hedyotis corymbosa L. promotes another anticancer properties by inhibiting migration and metastasis towards breast cancer cells.Keywords : Hedyotis corymbosa L., cytotoxicity, migration, metastatic, 4T1 breast cancer cell
Pentagamavunone-0 (PGV-0), a Curcumin Analog, Enhances Cytotoxicity of 5-Fluorouracil and Modulates Cell Cycle in WiDr Colon Cancer Cells
Full text linkThe use of 5-fluorouracil (5-FU) in colon cancer as the primary chemotherapy has not been meet satisfactory effectiveness. Therefore, the development of new chemicals as a chemopreventive agent and a combination agent (co-chemotherapeutic agent) for colon cancer is important. Pentagamavunone-0 (2,5-bis-(4'-hydroxy-3'-methoxybenzylidine) cyclopentanone) (PGV-0), one of curcumin analogs, exhibits cytotoxic effect and apoptosis induction in various cancer cell lines, including colon cancer cell, better than curcumin. This study aimed to investigate the cytotoxic potency of PGV-0 in combination with 5-FU and their effects, in single or in combination, on cell cycle toward WiDr colon cancer cell line. The cells were treated with combination concentrations of PGV-0 and 5-FU, and examined by MTT cell viability assay. The value of combination index (CI) as a parameter of cytotoxic combination assay was measured by a combination index method. Cells were stained with propidium iodide and the cell cycle distribution was determined by flowcytometry. CI calculation showed additive effects between PGV-0 and 5-FU. Combination of PGV-0 and 5-FU gave synergism on cell cycle. Single treatment of PGV-0 increased apoptosis, illustrated as subG1-phase accumulation, stronger than single treatment of 5-FU. Meanwhile, combination of PGV-0 and 5-FU demonstrated S-phase arrest. Based on these results, it can be concluded that PGV-0 has the potential to be developed as a co-chemotherapeutic agent for colon cancer but still requires further tracking of its molecular mechanisms.Keywords: Pentagamavunone-0 (PGV-0), 5-fluorouracil (5-FU), colon cancer,combination, cell cycl
Anti-metastatic Profiles of Boesenbergia pandurata towards MCF-7/HER2 Cells
Full text linkThe development of breast cancer at an advanced stage is signed with metastatic phenomenon, triggering the high mortality, mainly for Human Epidermal Growth Factor Receptor (HER)2 positive cancers. Boesenbergia pandurata is well known as medicinal plant possessing anticancer potential due to the cytototoxic and antimetastatic characteristic of its active compound. The aim of this study is to observe the inhibitory effect of Boesenbergia pandurata ethanolic extract (BPEE) in combination with doxorubicin on migration of MCF-7/HER2 cells. The BPEE was prepared by 96% ethanol maceration. Under MTT assay, BPEE decreased the cells viability with IC50 value of 23±3.9 μg/mL. Lamellipodia and wound healing assay analysis showed that 5 μg/mL BPPE and its combination with 10 nM doxorubicin inhibited cells migration after 48 hours observation, while gelatin zymography analysis showed that this combination did not affect the expression of Matrix Metalloproteinase (MMP)2 and MMP9, but single treatment of 5 μg/mL BPEE caused lower expression of both MMPs. The combination of 5 μg/mL BPPE and 10 nM doxorubicin inhibited the cells migration but not affect to the cells viability. Thus, BPEE is potential to be developed as an antimetastatic agent. The mechanism underlying the migratory inhibition effect needs to be explored further.Keywords : Boesenbergia pandurata, doxorubicin, MCF-7/HER2, migrationSubmitted
Trigona sp. Propolis Ethanolic Extract Decreased Chloramphenicol-induced Serum Glutamic Oxaloacetic Transaminase and Alkaline Phosphatase Levels of Rats (Rattus novergicus)
Full text linkLiver has an important role in detoxification of toxins such as xenobiotic which could interfere the function of liver. Chloramphenicol is an antibiotic widely used,despite of its toxicity potentials. The enhancement of free radicals in the body could suppress antioxidant activity. Propolis of Trigona sp. has been known to contain very high amount of antioxidants. The enhanced serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase (ALP) levels in serum is used as marker of liver damage due to the increase of free radicals. The purpose of this study was to observe the effect of Trigona sp. propolis ethanolic extract on SGOT and ALP levels in rats (Rattus novergicus) pretreated by chloramphenicol to induce liver damage. Test animals used for this research were male rats aged 8-12 weeks divided into five treatment groups: negative controlgroup (normal), positive control group (induced by 400 mg/kgBW chloramphenicol), first therapy group, second therapy group, third therapy group induced by chloramphenicol with and propolis extract with the dose of 8 mg, 16 mg, and 24 mg, respectively. Chloramphenicol was injected subcutaneously for 14 days, whereas propolis extract were administered orally for 21 days. The level of SGOT and ALP was determined using spectophotometry. The results showed that propolis extract could reduce levels of SGOT and ALP. Dose of 24 mg/kg was the effective dose to decrease levels of SGOT and ALP significantly (p<0.01). Hence, it may be concluded that the ethanol extract of propolis could be used as herbal therapy in rats model of liver damage.Keywords : ALP, liver, chloramphenicol, propolis, SGO
Enhancement of Cytotoxicity and Apoptosis Induction of Doxorubicin by Brazilein Containing Fraction of Secang (Caesalpinia sappan L.) on T47D Cells
Full text linkCombination chemotherapy (co-chemotherapy) is a recent strategy to reduce the toxicity effect and increase the effectivity of chemotherapeutic agent, such as Doxorubicin (Dox). Caesalpinia sappan L. are potential to be developed as co-chemoterapeutic agents due to its strong cytotoxicity toward several breast cancer cells. The purpose of this research is to observe the cytotoxicity of Brazilein containing fraction (BCF) in single and its combination with doxorubicin on T47D cells. BCF was obtained by fractionation using chloroform:ethyl acetate (40:60 v/v) as mobile phase. Molecular docking results showed that Brazilein and Brazilin interacted with Bcl-2 with different binding properties. Based on MTT assay, Dox and BCF performed potent cytotoxicity with IC50 value of 403 nM and 68 μg/mL, respectively. BCF increased the cytotoxicity of Dox and performed synergism with CI value 1. Under Annexin V PI staining Flowcytometry, BCF in single and its combination with doxorubicin induced apoptosis. In conclusion, single treatment of BCF and its combination with Dox performed cytotoxic effect and induced apoptosis on T47D cell lines.Keywords: Brazilein containing fraction, Doxorubicin, Co-chemoteraphy, Apoptosis, T47D cell
The Cytoprotective and Cell Recovery Properties of Apple Extracts on H2O2 induced-NIH3T3 Cells: An Anti Aging Candidate
Full text linkApple contains high concentration of phenolic compounds that protect cells from oxidative stress. The prolong exposure of free radicals may induce cell damage and premature cell aging. Both local and imported apple contain flavonoid, saponin, tannin, steroid, and terpenoid. The extract of local and imported apples showed low toxicity on NIH3T3 fibroblast cells, with IC50 value of 529 and 463 µg/mL, respectively. Both apple extracts (50 – 250 µg /mL) protected three-day-H2O2 induced-cell damage and cell death. Protective effect was observed as the viability increase of treated cells compared to untreated ones. The protective effect of both extracts were higher than the effect of vitamin C as standard antioxidant at this study. Both apple extracts could reverse cell damage caused by three-hour-high concentration H2O2 exposure, similar with vitamin C. Low concentration of both extracts (50 µg /mL) induced the increase of fibroblast cells’ proliferation kinetics. The extract of imported apple showed higher properties of protective, cell recovery and proliferation of fibroblast cells tha local apple, but not statistically significance. This study concludes that the extract of local and imported apples have high potency in cytoprotective effect and cell recovery of damaged cells caused by free radicals induction. Both apple extracts have high potency to be developed the candidate of antiaging and cells’ regeneration agent.Keywords : antiaging, cell recovery, cytoprotective, NIH3T3 cell
Bridging the Gap between TGF-β/Smad Signalling and Tumorigenesis Arising from Clonorchis sinensis Induced Hepatic Fibrosis
Full text linkClonorchiasis is a parasitic infection caused by food borne trematode, Clonorchis sinensis that is mainly prevalent in Asian countries, including South Korea, China, northern Vietnam, Japan, as well as far-eastern Russia, in which over 35 million people are the casualties. Clonorchiasis is characterized by the development of hepatic fibrosis. Upon chronic liver injury following the C. sinensis infection, hepatic fibrosis develops into cholangiocarcinoma with a concomitant genetic and epigenetic mutations. Cholangiocarcinoma represents important clinical manifestation of C. sinensis infection and causes high rate of morbidity. TGF- β/Smad signalling is known to initiate hepatic fibrosis following the hepatic injury. However, little is known about the role of TGF- β/Smad signalling during C. sinensis induced hepatic injury and the underlying contribution of TGF- β/Smad signalling in the development of cholangicarcinoma. The expression dynamic of TGF-β/Smad signalling and their role in the development of hepatic fibrosis in C. sinensis infected BALB/c mice have been investigated. Concomitantly but irrespective to C. sinensis infection, the role of hepatic epithelial TGF-β during hepatic fibrosis and the development of cholangiocarcinoma arising from hepatic epithelial cells have also been dissected. Both findings will be reviewed in this paper. Thereby, the link between TGF-β/Smad signalling, hepatic fibrosis during C sinensis infection, and cholangiocarcinoma could be drawn clearly.Keywords: Clonorchis sinensis, TGF-β/Smad signalling, Hepatic fibrosis, Cholangiocarcinom