curcumin and Retinoblastoma

Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases.

Topics: Animals; Anti-Inflammatory Agents; Clinical Trials as Topic; Curcuma; Curcumin; Diabetic Retinopathy; Disease Models, Animal; Glaucoma; Humans; Inflammation; Macular Degeneration; Retinal Diseases; Retinitis Pigmentosa; Retinoblastoma; Vitreoretinopathy, Proliferative

To study the effect of curcumin on proliferation and invasion of the human retinoblastoma cells and its potential mechanism.. A cell line of retinoblastoma (WERI-Rb-1) was treated with various concentrations of curcumin (0-40 µM). Cell number was counted with CCK8 kit, and cell migration was assessed using the Transwell assay. Immunoblotting was performed to detect the proteins of metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) as well as nuclear translocation of nuclear factor-κB (NF-κB, p65).. Proliferation and migration of WERI-Rb-1 cells were significantly inhibited by curcumin in a concentration-dependent manner (0-40 µM). Protein expressions of MMP-2, MMP-9 and VEGF in the WERI-Rb-1 cells were also significantly inhibited by curcumin in a concentration-dependent manner (0-40 µM). Furthermore, nuclear translocation of NF-κB (p65) was significantly inhibited by curcumin in time-dependent manner (6-24 h).. Curcumin inhibited proliferation and migration of WERI-Rb-1 cells, a cell line of human retinoblastoma, which might be through modulating NF-κB and its downstream proteins including VEGF, MMP-2, and MMP-9.

Topics: Cell Line, Tumor; Cell Proliferation; Curcumin; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; NF-kappa B; Retinal Neoplasms; Retinoblastoma; Vascular Endothelial Growth Factor A

Curcumin, a primary active ingredient extracted from the Curcuma longa, has been recently identified as a potential anti-tumor agent in multiple kinds of cancers. However, the effect of curcumin on retinoblastoma (Rb) is still unclear. Therefore, we attempted to reveal the functional impacts and the underlying mechanisms of curcumin in Rb cells.. Two Rb cell lines SO-Rb50 and Y79 were pre-treated with various doses of curcumin, and then cell proliferation, apoptosis, migration, and invasion were assessed, respectively. Further, regulatory effects of curcumin on miR-99a expression, as well as the activation of JAK/STAT pathway were studied.. Data showed that curcumin significantly inhibited the viability, colony formation capacity, migration and invasion, while induced apoptosis of SO-Rb50 and Y79 cells. Up-regulation of miR-99a was observed in curcumin-treated cells. Curcumin suppressed the phosphorylation levels of JAK1, STAT1, and STAT3, while curcumin did not inhibit the activation of JAK/STAT pathway when miR-99a was knocked down.. Curcumin inhibited proliferation, migration, invasion, but promoted apoptosis of Rb cells. The anti-tumor activities of curcumin on Rb cells appeared to be via up-regulation of miR-99a, and thereby inhibition of JAK/STAT pathway.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Curcumin; Gene Expression Regulation, Neoplastic; Humans; Janus Kinases; MicroRNAs; Retinal Neoplasms; Retinoblastoma; Signal Transduction; STAT Transcription Factors

Curcumin, a naturally occurring polyphenolic compound present in turmeric (Curcuma longa), exerts antitumor effects in various types of malignancy. However, the precise mechanisms responsible for the effects of curcumin on retinoblastoma (RB) cells have not been fully explored. In the present study, the molecular mechanisms by which curcumin exerts its anticancer effects in RB Y79 cells were investigated. The results showed that curcumin reduced cell viability in Y79 cells. Curcumin induced G1 phase arrest through downregulating the expression of cyclin D3 and cyclin-dependent kinase (CDK)2/6 and upregulating the expression of CDK inhibitor proteins p21 and p27. Curcumin-induced apoptosis of Y79 cells occurred through the activation of caspases-9/-3. Moreover, flow cytometric analysis showed that curcumin induced mitochondrial membrane potential (∆Ψm) collapse in Y79 cells. We also found that curcumin induced the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). JNK and p38 MAPK inhibitors significantly suppressed curcumin‑induced activation of caspases-9/-3 and inhibited the apoptosis of Y79 cells. Taken together, our results suggest that curcumin induced the apoptosis of Y79 cells through the activation of JNK and p38 MAPK pathways. These findings provide a novel treatment strategy for human RB.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Caspase 3; Caspase 9; Cell Line, Tumor; Cell Survival; Curcumin; Dose-Response Relationship, Drug; Enzyme Activation; Flow Cytometry; G1 Phase Cell Cycle Checkpoints; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases; Retinoblastoma

Curcumin (diferuloylmethane), a phenolic compound obtained from the rhizome of the herb Curcuma longa, is known to have anti-proliferative and anti-tumor properties. In this study, we evaluated the cytotoxic effect of curcumin alone and in combination with individual drugs like carboplatin, etoposide, or vincristine in a human retinoblastoma (RB) cancer cell line.. A drug-drug interaction was analyzed using the median effect/isobologram method and combination index values were used to characterize the interaction as synergistic or additive. We also performed the apoptosis and cell-cycle kinetics study with single drugs in combination with curcumin in a human RB cell lines (Y79 and Weri-Rb1).. Curcumin caused concentration-dependent decrease in cell proliferation, cell kinetics, and also induced apoptosis in both the RB cell lines. When combination of curcumin with individual drugs like carboplatin or etoposide or vincristine was treated on to RB cells, both cell viability and cell cycling were reduced and increased apoptosis was noted, in comparison with single drug treatment. These effects were significant in both the cell lines, indicating the ability of curcumin to increase the sensitivity of RB cells to chemotherapy drugs.. Our in vitro findings showed that the combination of curcumin with single drug treatment showed marked synergistic inhibitory effect against RB cell lines. These results suggest that curcumin can be used as a modulator which may have a potential therapeutic value for the treatment of RB cancer patients.

Topics: Annexin A5; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carboplatin; Caspase 3; Cell Cycle; Cell Line, Tumor; Curcumin; Dose-Response Relationship, Drug; Drug Synergism; Etoposide; Humans; Retinal Neoplasms; Retinoblastoma; Vincristine

Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP) is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR) by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs) surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined) and single or dual drug loaded nanoparticles (unconjugated/folate conjugated). The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs) over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype.

Topics: Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Curcumin; Drug Carriers; Drug Resistance, Neoplasm; Folic Acid; Gene Expression Regulation, Neoplastic; Humans; Imidazoles; Lactic Acid; Membrane Potential, Mitochondrial; Multidrug Resistance-Associated Proteins; Nanoparticles; NF-kappa B; Piperazines; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Proto-Oncogene Proteins c-bcl-2; Retinoblastoma; Tumor Suppressor Protein p53

Curcumin, a well-known chemopreventive agent from turmeric, inhibits the expression of several oncogenes and cell proliferation genes in tumor cells. This study aims to understand the precise molecular mechanism by which curcumin exerts its effects on retinoblastoma cells, by performing whole genome microarray analysis to determine the gene expression profiles altered by curcumin treatment. Curcumin suppressed cell viability and altered the cell cycle of retinoblastoma cells. We identified 903 downregulated genes and 1,319 upregulated genes when compared with the control cells after treatment with 20 μM curcumin concentration for 48 h. These genes were grouped into respective functional categories according to their biological function. We found that curcumin regulated the expression of genes that are involved in the regulation of apoptosis, tumor suppressor, cell-cycle arrest, transcription factor, and angiogenesis. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to validate the results of genome array, and the results were consistent with the obtained data. In conclusion, treatment of curcumin affects the expression of genes involved in various cellular functions and plays an important role in tumor metastasis and apoptosis. Thus, curcumin might be an effective chemopreventive agent for retinoblastoma cancer.

Topics: Antioxidants; Apoptosis; Cell Cycle; Cell Division; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcuma; Curcumin; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Oligonucleotide Array Sequence Analysis; Plant Extracts; Real-Time Polymerase Chain Reaction; Retinoblastoma; RNA, Messenger; Transcriptome; Up-Regulation

Retinoblastoma (RB) is the most common intraocular malignancy in children. Deregulation of several miRNAs has been identified in RB, suggesting a potential role in tumorigenesis. Recent evidence suggests that many dietary components like folate, retinoids and curcumin act as potential anticancer/antiproliferative agents by regulating the expression of miRNA. In this study, we investigated the effect of phenolic compound curcumin on miRNA expression in Y79 RB cells.. We analyzed the expression profile of miRNA by microarray analysis and quantitative real-time polymerase chain reaction (qRT-PCR) in curcumin-treated Y79 RB cells. Transfection of miR-22 was performed using Lipofectamine 2000. Cell viability, in vitro scratch migration assay, prediction of miRNA targets and Western blot analysis were performed to determine the biological function of miR-22 in Y79 RB cells.. In Y79 RB cells treated with curcumin, 5 human miRNAs were upregulated and 16 were downregulated as detected with the miRNA microarray analysis. miR-22, a tumor-suppressor miRNA was one of the miRNA which was upregulated by curcumin. Transfected miR-22 Y79 cells inhibited the cell proliferation and reduced the migration, and erythoblastic leukemia viral oncogene homolog 3 (Erbb3) was confirmed to be the target gene of miR-22.. These observations suggest that curcumin modulate the miRNA expression profile, thereby exerting its anticancer effects on RB cells.

Topics: Antineoplastic Agents; Blotting, Western; Cell Survival; Curcumin; Gene Expression Regulation, Neoplastic; Genes, Retinoblastoma; Humans; MicroRNAs; Real-Time Polymerase Chain Reaction; Retina; Retinal Neoplasms; Retinoblastoma; Tumor Cells, Cultured

Multidrug resistance to anticancer drugs is a major cause of chemotherapy failure in cancer patients. Lung resistance-related protein (LRP) has been identified as the major vault protein (MVP) in humans, which is associated with multidrug resistance in various cancer cells. Overexpression of LRP is found in many solid tumors and cancer cell lines.. In this study, curcumin mixture was used to study the modulation of LRP in Y79 retinoblastoma cell line by Western blot and RT-PCR.. RT-PCR and Western blot was carried to determine the expression of LRP mRNA and protein level. Western blot and RT-PCR analysis showed that curcumin inhibited LRP expression in a dose-dependent manner in the Y79 retinoblastoma cell line.. These results demonstrate that curcumin modulated the expression of LRP in the Y79 retinoblastoma cell line. Thus, curcumin may be used as a chemosensitizer to make the retinoblastoma cells more sensitive to the effects of chemotherapy.

Topics: Antineoplastic Agents; Blotting, Western; Cell Line, Transformed; Curcumin; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Retinal Neoplasms; Retinoblastoma; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vault Ribonucleoprotein Particles