10 results on '"Kuruppu AI"'
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2. Exploring the Bioactive Potential of Exotic Fruits from Sri Lanka: A Treasure Trove of Medicinal Properties.
- Author
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Dissanayake DMDS, Heshani IGS, Hassan S, and Kuruppu AI
- Abstract
Tropical fruits are often studied to determine their content of bioactive compounds that contain health-enhancing properties and are often identified to hold a rich nutritional composition. Their bioactive compounds are classified through their phenolic, flavonoid, and antioxidant properties, while some tropical fruits are known to have other properties such as anticancer and anti-inflammatory activity. Sri Lanka is an island with abundant resources. One such resource is exotic fruits. Exotic fruits are known as edible fruits, which are not necessarily native but consist of a unique flavor profile, fragrance, shape, or appearance. Exotic fruits are usually consumed on their own or consumed as beverages, pickles, jams, salads, and desserts. The market-friendly tropical fruits in Sri Lanka include a vast number, and some of them are mango, Ceylon olives, durian, jackfruit, rambutan, soursop, passion fruit, and star fruit. These fruits contribute to the rice culinary heritage of Sri Lanka, and most of them are exported worldwide. At present, the traditional medicine system is quite popular among the public due to its less toxic nature and easy access. This review is aimed at evaluating the antioxidant, cytotoxic, anticancer, and anti-inflammatory properties of eight selected exotic fruits mentioned above and their traditional usage, which is based on the literature of various scientific studies conducted on these tropical fruits., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
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3. Structural Characterization and Anti-Inflammatory Effects of 24-Methylcholesta-5(6), 22-Diene-3β-ol from the Cultured Marine Diatom Phaeodactylum tricornutum ; Attenuate Inflammatory Signaling Pathways.
- Author
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Samarakoon KW, Kuruppu AI, Ko JY, Lee JH, and Jeon YJ
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- Animals, Zebrafish metabolism, NF-kappa B metabolism, Lipopolysaccharides pharmacology, Anti-Inflammatory Agents pharmacology, Signal Transduction, Cytokines metabolism, Interleukin-6 metabolism, Nitric Oxide metabolism, Nitric Oxide Synthase Type II metabolism, Cyclooxygenase 2 metabolism, Diatoms metabolism
- Abstract
In the present investigation, 24-methylcholesta-5(6), 22-diene-3β-ol (MCDO), a major phytosterol was isolated from the cultured marine diatom, Phaeodactylum tricornutum Bohlin, and in vitro and in vivo anti-inflammatory effects were determined. MCDO demonstrated very potent dose-dependent inhibitory effects on the production of nitric oxide (NO) and prostaglandin E
2 (PGE2 ) against lipopolysaccharide (LPS)-induced RAW 264.7 cells with minimal cytotoxic effects. MCDO also demonstrated a strong and significant suppression of pro-inflammatory cytokines of interleukin-1β (IL-1β) production, but no substantial inhibitory effects were observed on the production of cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at the tested concentrations against LPS treatment on RAW macrophages. Western blot assay confirmed the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions against LPS-stimulated RAW 264.7 cells. In addition, MCDO was assessed for in vivo anti-inflammatory effects using the zebrafish model. MCDO acted as a potent inhibitor for reactive oxygen species (ROS) and NO levels with a protective effect against the oxidative stress induced by LPS in inflammatory zebrafish embryos. Collectively, MCDO isolated from the cultured marine diatom P. tricornutum exhibited profound anti-inflammatory effects both in vitro and in vivo, suggesting that this major sterol might be a potential treatment for inflammatory diseases.- Published
- 2023
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4. Apoferritin and Dps as drug delivery vehicles: Some selected examples in oncology.
- Author
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Kuruppu AI, Turyanska L, Bradshaw TD, Manickam S, Galhena BP, Paranagama P, and De Silva R
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- Humans, Animals, Drug Carriers chemistry, Nanoparticles chemistry, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Iron-Binding Proteins metabolism, Iron-Binding Proteins chemistry, Iron metabolism, Iron chemistry, Apoferritins chemistry, Apoferritins metabolism, Neoplasms drug therapy, Neoplasms metabolism, Drug Delivery Systems methods
- Abstract
Background: The ideal nanoparticle should be able to encapsulate either pharmaceutical agents or imaging probes so that it could treat or image clinical tumours by targeting the cancer site efficiently. Further, it would be an added advantage if it demonstrates: small size, built in targeting, biocompatibility and biodegradability. Ferritin, which is an endogenous self-assembling protein, stores iron and plays a role in iron homeostasis. When iron atoms are removed apoferritin (AFt) is formed which consists of a hollow shell where it can be used to load guest molecules. Due to its unique architecture, AFt has been investigated as a versatile carrier for tumour theranostic applications. DNA-binding protein from starved cells (Dps), which also belongs to the ferritin family, is a protein found only in prokaryotes. It is used to store iron and protect chromosomes from oxidative damage; because of its architecture, Dps could also be used as a delivery vehicle., Conclusions: Both these nano particles are promising in the field of oncology, especially due to their stability, solubility and biocompatibility features. Further their exterior surface can be modified for better tumour-targeting ability. More studies, are warranted to determine the immunogenicity, biodistribution, and clearance from the body., General Perspective: This review discusses a few selected examples of the remarkable in vitro and in vivo studies that have been carried out in the recent past with the use of AFt and Dps in targeting and delivery of various pharmaceutical agents, natural products and imaging probes in the field of oncology., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2022
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5. Medicinal plants commonly used against cancer in traditional medicine formulae in Sri Lanka.
- Author
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Kuruppu AI, Paranagama P, and Goonasekara CL
- Abstract
Cancer is a global burden. In low- and middle-income countries around 70% of deaths are due to cancer. For a number of years natural products have been a good source of agents for combatting cancer and plants have played a huge role in anti-cancer product development. For many centuries, indigenous cultures around the world have used traditional herbal medicine to treat a myriad of diseases including cancer. In Sri Lanka, a number of plants have been reported to have anti-cancer properties and some of the commonly used plants are described in this review with an account of their compounds and modes of action. Only a small number of the plants in Sri Lanka have been tested for their bioactivity and more research is required to determine their medicinal activity with the aim of developing novel drugs to fight this disease.
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- 2019
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6. Genetic Variants Associated with Clinicopathological Profiles in Sporadic Breast Cancer in Sri Lankan Women.
- Author
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Sirisena ND, Adeyemo A, Kuruppu AI, Samaranayake N, and Dissanayake VHW
- Abstract
Purpose: Several single nucleotide polymorphisms (SNPs) have been reported to be associated with clinicopathological profiles in sporadic breast cancer based on studies conducted on major population groups. The knowledge of the effects of these common genetic variants in South Asian populations remains limited. The present study aimed to investigate the association between a selected set of SNPs and the clinicopathological profiles in sporadic breast cancer in Sri Lankan women., Methods: A total of 350 postmenopausal women with histologically confirmed invasive breast cancer were genotyped for 58 SNPs located in 36 breast cancer related genes. The clinicopathological factors that were investigated included age of onset, tumor histologic grade, and lymph node involvement, as well as estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status. Association testing was performed using logistic regression models adjusted for confounding factors., Results: Seven SNPs showed significant associations with clinicopathological profiles in breast cancer. The G allele of BRCA1 :rs799917 ( p =0.047; β [standard error; SE]=-1.069 [0.537]) and the G allele of NQO2 :rs17136117 ( p =0.040, β [SE]=1.901 [0.923]) were found to be associated with age of onset between 50 and 59 years. The C allele of CDH1 :rs13689 (odds ratio [OR], 2.121; p =0.033) was found to be associated with ER-positive breast cancer. The A allele of AKT1 :rs1130214 (OR, 2.095; p =0.011) and the C allele of NQO2 :rs2071002 (OR, 1.632; p =0.045) were associated with HER2-positive breast cancer. The C allele of BRCA2 :rs15869 (OR, 1.600; p =0.041) and the C allele of CCND1 :rs7177 (OR, 1.555; p =0.041) were associated with high tumor histologic grade., Conclusion: The common genetic variants identified in the AKT1 , BRCA1 , BRCA2 , CCND1 , CDH1 , and NQO2 genes could serve as potential clinical and prognostic biomarkers in sporadic breast cancer patients. Further studies are required to validate our current findings in other populations., Competing Interests: CONFLICT OF INTEREST: The authors declare that they have no competing interests. The funding bodies did not play any role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
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- 2018
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7. Genetic determinants of sporadic breast cancer in Sri Lankan women.
- Author
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Sirisena ND, Adeyemo A, Kuruppu AI, Neththikumara N, Samaranayake N, and Dissanayake VHW
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- Aged, Aged, 80 and over, Antigens, CD, Ataxia Telangiectasia Mutated Proteins genetics, Breast Neoplasms pathology, Cadherins genetics, Case-Control Studies, DNA-Binding Proteins genetics, Female, Genotype, Humans, Logistic Models, Middle Aged, Prohibitins, Repressor Proteins genetics, Risk Factors, Sri Lanka, Breast Neoplasms genetics, Genetic Predisposition to Disease genetics, Polymorphism, Single Nucleotide, Postmenopause
- Abstract
Background: While a range of common genetic variants have been identified to be associated with risk of sporadic breast cancer in several Western studies, little is known about their role in South Asian populations. Our objective was to examine the association between common genetic variants in breast cancer related genes and risk of breast cancer in a cohort of Sri Lankan women., Methods: A case-control study of 350 postmenopausal women with breast cancer and 350 healthy postmenopausal women was conducted. Genotyping using the iPLEX GOLD assay was done for 56 haplotype-tagging single nucleotide polymorphisms (SNPs) in 36 breast cancer related genes. Testing for association was done using an additive genetic model. Odds ratios and 95% confidence intervals were calculated using adjusted logistic regression models., Results: Four SNPs [rs3218550 (XRCC2), rs6917 (PHB), rs1801516 (ATM), and rs13689 (CDH1)] were significantly associated with risk of breast cancer. The rs3218550 T allele and rs6917 A allele increased breast cancer risk by 1.5-fold and 1.4-fold, respectively. The CTC haplotype defined by the SNPs rs3218552|rs3218550|rs3218536 on chromosome 7 (P = 0.0088) and the CA haplotype defined by the SNPs rs1049620|rs6917 on chromosome 17 (P = 0.0067) were significantly associated with increased risk of breast cancer. The rs1801516 A allele and the rs13689 C allele decreased breast cancer risk by 0.6-fold and 0.7-fold, respectively., Conclusions: These findings suggest that common genetic polymorphisms in the XRCC2, PHB, CDH1 and ATM genes are associated with risk of breast cancer among Sri Lankan postmenopausal women. The exact biological mechanisms of how these variants regulate overall breast cancer risk need further evaluation using functional studies.
- Published
- 2018
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8. In Vitro Antitumor Effects of AHR Ligands Aminoflavone (AFP 464) and Benzothiazole (5F 203) in Human Renal Carcinoma Cells.
- Author
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Luzzani GA, Callero MA, Kuruppu AI, Trapani V, Flumian C, Todaro L, Bradshaw TD, and Loaiza Perez AI
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- Carcinoma, Renal Cell metabolism, Carcinoma, Renal Cell pathology, Cell Line, Tumor, Humans, Kidney Neoplasms metabolism, Kidney Neoplasms pathology, Neoplasm Proteins metabolism, Receptors, Aryl Hydrocarbon metabolism, Signal Transduction drug effects, Antineoplastic Agents pharmacology, Carcinoma, Renal Cell drug therapy, Flavonoids pharmacology, Kidney Neoplasms drug therapy, Neoplasm Proteins agonists, Receptors, Aryl Hydrocarbon agonists, Thiazoles pharmacology
- Abstract
We investigated activity and mechanism of action of two AhR ligand antitumor agents, AFP 464 and 5F 203 on human renal cancer cells, specifically examining their effects on cell cycle progression, apoptosis, and migration. TK-10, SN12C, Caki-1, and ACHN human renal cancer cell lines were treated with AFP 464 and 5F 203. We evaluated cytotoxicity by MTS assays, cell cycle arrest, and apoptosis by flow cytometry and corroborated a mechanism of action involving AhR signal transduction activation. Changes in migration properties by wound healing assays were investigated: 5F 203-sensitive cells show decreased migration after treatment, therefore, we measured c-Met phosphorylation by Western blot in these cells. A 5F 203 induced a decrease in cell viability which was more marked than AFP 464. This cytotoxicity was reduced after treatment with the AhR inhibitor α-NF for both compounds indicating AhR signaling activation plays a role in the mechanism of action. A 5F 203 is sequestered by TK-10 cells and induces CYP1A1 expression; 5F 203 potently inhibited migration of TK-10, Caki-1, and SN12C cells, and inhibited c-Met receptor phosphorylation in TK-10 cells. AhR ligand antitumor agents AFP 464 and 5F 203 represent potential new candidates for the treatment of renal cancer. A 5F 203 only inhibited migration of sensitive cells and c-Met receptor phosphorylation in TK-10 cells. c-Met receptor signal transduction is important in migration and metastasis. Therefore, we consider that 5F 203 offers potential for the treatment of metastatic renal carcinoma. J. Cell. Biochem. 118: 4526-4535, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
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9. Horner-Wadsworth-Emmons approach to piperlongumine analogues with potent anti-cancer activity.
- Author
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Han LC, Stanley PA, Wood PJ, Sharma P, Kuruppu AI, Bradshaw TD, and Moses JE
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- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Line, Tumor, Cell Proliferation drug effects, Dioxolanes chemical synthesis, Dioxolanes chemistry, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Molecular Structure, Reactive Oxygen Species metabolism, Structure-Activity Relationship, Antineoplastic Agents pharmacology, Dioxolanes pharmacology
- Abstract
Natural products with anti-cancer activity play a vital role in lead and target discovery. We report here the synthesis and biological evaluation of the plant-derived alkaloid, piperlongumine and analogues. Using a Horner-Wadsworth-Emmons coupling approach, a selection of piperlongumine-like compounds were prepared in good overall yield from a novel phosphonoacetamide reagent. A number of the compounds displayed potent anti-cancer activity against colorectal (HCT 116) and ovarian (IGROV-1) carcinoma cell lines, via a mechanism of action which may involve ROS generation. Contrary to previous reports, no selective action in cancer cell (MRC-5) was observed for piperlongumine analogues.
- Published
- 2016
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10. An Apoferritin-based Drug Delivery System for the Tyrosine Kinase Inhibitor Gefitinib.
- Author
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Kuruppu AI, Zhang L, Collins H, Turyanska L, Thomas NR, and Bradshaw TD
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- Cell Line, Tumor, Endocytosis drug effects, Gefitinib, Humans, Apoferritins metabolism, Drug Delivery Systems methods, Protein Kinase Inhibitors pharmacology, Quinazolines pharmacology
- Abstract
Anticancer drug Gefitinib encapsulated within human heavy chain apoferritin by diffusion allows pH-controlled sustained release of cargo. The combination of increased cellular uptake, and potent and enhanced antitumor activity against the HER2 overexpressing SKBR3 cell line compared to Gefitinib alone, makes it a promising carrier for delivery of drugs to tumor sites., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
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