Publications by authors named "Premdass Ramdas"

7 Publications

  • Page 1 of 1

Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation.

Clin Exp Immunol 2021 Nov 18;206(2):161-172. Epub 2021 Aug 18.

Pathology Division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia.

Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T helper (Th) and T regulatory cell (T ) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2 weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were euthanized. Mice (n = 6) were euthanized at specified time-points for various analysis (blood leucocyte, cytokine production and immunohistochemistry). Tumour volume was measured once every 7 days. Gene expression studies were carried out on tumour-specific T lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4 (p < 0.05), CD8 (p < 0.05) T-cells and natural killer cells (p < 0.05) but suppressed T cells (p < 0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon (IFN)-γ and lower transforming growth factor (TGF)-ꞵ levels were noted in the γT3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4 cells, increased expression of interleukin-12 receptor-beta-2 (IL-12ꞵ2R), interleukin (IL)-24 and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the γT3-fed animals. Gene expression studies showed the down-regulation of seven prominent genes in splenic CD4 T cells isolated from γT3-fed mice. Supplementation with γT3 from palm oil-induced T cell-dependent cell-mediated immune responses and suppressed T cells in the tumour microenvironment in a syngeneic mouse model of breast cancer.
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http://dx.doi.org/10.1111/cei.13650DOI Listing
November 2021

Tocotrienols Ameliorate Neurodegeneration and Motor Deficits in the 6-OHDA-Induced Rat Model of Parkinsonism: Behavioural and Immunohistochemistry Analysis.

Nutrients 2021 May 10;13(5). Epub 2021 May 10.

College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.

Parkinson's disease (PD) is a debilitating neurodegenerative disease, which progresses over time, causing pathological depigmentation of the substantia nigra (SN) in the midbrain due to loss of dopaminergic neurons. Emerging studies revealed the promising effects of some nutrient compounds in reducing the risk of PD. One such nutrient compound that possess neuroprotective effects and prevents neurodegeneration is tocotrienol (T3), a vitamin E family member. In the present study, a single dose intracisternal injection of 250 µg 6-hydroxydopamine (6-OHDA) was used to induce parkinsonism in male Sprague Dawley (SD) rats. Forty-eight hours post injection, the SD rats were orally supplemented with alpha (α)- and gamma (γ)-T3 for 28 days. The neuroprotective effects of α- and γ-T3 were evaluated using behavioural studies and immunohistochemistry (IHC). The findings from this study revealed that supplementation of α- and γ-T3 was able to ameliorate the motor deficits induced by 6-OHDA and improve the neuronal functions by reducing inflammation, reversing the neuronal degradation, and preventing further reduction of dopaminergic neurons in the SN and striatum (STR) fibre density.
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http://dx.doi.org/10.3390/nu13051583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150907PMC
May 2021

Advancing the Role of Gamma-Tocotrienol as Proteasomes Inhibitor: A Quantitative Proteomic Analysis of MDA-MB-231 Human Breast Cancer Cells.

Biomolecules 2019 12 21;10(1). Epub 2019 Dec 21.

Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Tocotrienol, an analogue of vitamin E has been known for its numerous health benefits and anti-cancer effects. Of the four isoforms of tocotrienols, gamma-tocotrienol (γT3) has been frequently reported for their superior anti-tumorigenic activity in both in vitro and in vivo studies, when compared to its counterparts. In this study, the effect of γT3 treatment in the cytoplasmic and nuclear fraction of MDA-MB-231 human breast cancer cells were assessed using the label-free quantitative proteomics analysis. The cytoplasmic proteome results revealed the ability of γT3 to inhibit a group of proteasome proteins such as PSMA, PSMB, PSMD, and PSME. The inhibition of proteasome proteins is known to induce apoptosis in cancer cells. As such, the findings from this study suggest γT3 as a potential proteasome inhibitor that can overcome deficiencies in growth-inhibitory or pro-apoptotic molecules in breast cancer cells. The nuclear proteome results revealed the involvement of important nuclear protein complexes which hardwire the anti-tumorigenesis mechanism in breast cancer following γT3 treatment. In conclusion, this study uncovered the advancing roles of γT3 as potential proteasomes inhibitor that can be used for the treatment of breast cancer.
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http://dx.doi.org/10.3390/biom10010019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022772PMC
December 2019

Tocotrienols Modulate Breast Cancer Secretomes and Affect Cancer-Signaling Pathways in MDA-MB-231 Cells: A Label-Free Quantitative Proteomic Analysis.

Nutr Cancer 2019 14;71(8):1263-1271. Epub 2019 May 14.

Department of Molecular Medicine, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.

Tocotrienols (T3), a family of vitamin E, are reported to possess potent anti-cancer effects but the molecular mechanisms behind these effects still remain unclear. The aim of this study was to investigate how T3 exert anti-cancer effects on MDA-MB-231 human breast cancer cells. The MDA-MB-231 cells were chosen for this study as they are triple-negative and highly metastatic cells, which form aggressive tumors in experimental models. The MDA-MB-231 cells were treated with varying concentrations (0-20 µg mL) of gamma (γ) or delta (δ) T3 and the secretome profiles of these cells treated with half maximal inhibitory concentration (IC) of γT3 (5.8 µg mL) or δT3 (4.0 µg mL) were determined using label-free quantitative proteomic strategy. A total of 103, 174 and 141 proteins were identified with ProteinLynx Global Server (PLGS) score of more than 200 and above 25% sequence coverage in the untreated control and T3-treated cell culture supernatant respectively. A total of 18 proteins were dysregulated between untreated control and T3 (δT3 or γT3) treated conditions. The results showed that T3 treatment downregulated the exogenous Cathepsin D and Serpine1 proteins but upregulated Profilin-1 protein, which play a key role in breast cancer in the MDA-MB-231 cells. These findings strongly suggest that T3 may induce differential expression of secreted proteins involved in the cytoskeletal regulation of RHO GTPase signaling pathway.
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http://dx.doi.org/10.1080/01635581.2019.1607407DOI Listing
July 2020

Modulatory effects of mesenchymal stem cells on leucocytes and leukemic cells: A double-edged sword?

Blood Cells Mol Dis 2015 Dec 1;55(4):351-7. Epub 2015 Aug 1.

Division of Pathology, Faculty of Medicine and Health Sciences, International Medical University, Malaysia. Electronic address:

Mesenchymal stem cells (MSCs) have drawn much attention amongst stem cell researchers in the past few decades. The ability of the MSC to differentiate into cells of mesodermal and non-mesodermal origins has made them an attractive approach for cell-based therapy and regenerative medicine. The MSCs have immunosuppressive activities that may have considerable therapeutic values in autoimmune diseases. However, despite the many beneficial effects reported, there is a growing body of evidence, which suggests that MSCs could be a culprit of enhanced tumour growth, metastasis and drug resistance in leukaemia, via some modulatory effects. Many controversies regarding the interactions between MSCs and leukaemia still exist. Furthermore, the role of MSCs in leukemogenesis and its progression remain largely unknown. Hence it is important to understand how the MSCs modulate leukaemia before these cells could be safely used in the treatment of leukaemia patients.
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http://dx.doi.org/10.1016/j.bcmd.2015.07.017DOI Listing
December 2015

Quercetin glycosides induced neuroprotection by changes in the gene expression in a cellular model of Parkinson's disease.

J Mol Neurosci 2015 Mar 17;55(3):609-17. Epub 2014 Aug 17.

Department of Pathology, Faculty of Medicine, International Medical University, Kuala Lumpur, Malaysia.

Quercetin glycosides, rutin and isoquercitrin, are potent antioxidants that have been found to possess neuroprotective effect in diseases like Parkinson's and Alzheimer's disease. In the present study, we have examined the gene expression changes with rutin and isoquercitrin pretreatment on 6-hydroxydopamine (6-OHDA)-treated toxicity in rat pheochromocytoma (PC12) cells. PC12 cells were pretreated with rutin or isoquercitrin and subsequently exposed to 6-OHDA. Rutin-pretreated PC12 attenuated the Park2, Park5, Park7, Casp3, and Casp7 genes which were expressed significantly in the 6-OHDA-treated PC12 cells. Rutin upregulated the TH gene which is important in dopamine biosynthesis, but isoquercitrin pretreatment did not affect the expression of this gene. Both rutin and isoquercitrin pretreatments upregulated the ion transport and antiapoptotic genes (NSF and Opa1). The qPCR array data were further validated by qRT-PCR using four primers, Park5, Park7, Casp3, and TH. This finding suggests that changes in the expression levels of transcripts encoded by genes that participate in ubiquitin pathway and dopamine biosynthesis may be involved in Parkinson's disease.
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http://dx.doi.org/10.1007/s12031-014-0400-xDOI Listing
March 2015

Tocotrienol-treated MCF-7 human breast cancer cells show down-regulation of API5 and up-regulation of MIG6 genes.

Cancer Genomics Proteomics 2011 Jan-Feb;8(1):19-31

Department of Human Biology, Faculty of Medicine and Health, International Medical University, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.

Background: Tocotrienols belong to the vitamin E family and have multiple anticancer effects, such as antiproliferative, antioxidant, pro-apoptosis and antimetastatic. This study aimed to identify the genes that are regulated in human breast cancer cells following exposure to various isomers of vitamin E as these may be potential targets for the treatment of breast cancer.

Materials And Methods: Gene expression profiling was performed with MCF-7 cells at inhibitory conditions of IC(50) using Illumina's Sentrix Array Human-6 BeadChips. The expression levels of selected differentially expressed genes were verified by quantitative real-time-PCR (qRT-PCR).

Results: The treatment with tocotrienol-rich palm oil fraction (TRF), α-tocopherol and isomers of tocotrienols (α, γ, and δ) altered the expression of several genes that code for proteins involved in the regulation of immune response, tumour growth and metastatic suppression, apoptotic signalling, transcription, protein biosynthesis regulation and many others.

Conclusion: Treatment of human MCF-7 cells with tocotrienol isomers causes the down-regulation of the API5 gene and up-regulation of the MIG6 gene and the differential expression of other genes reported to play a key role in breast cancer biology.
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April 2011
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