MyMedR

Displaying all 17 publications

Abstract:

Sort:

Serum folate concentration, cognitive impairment, and DNA damage among elderly individuals in Malaysia

Lee LK, Shahar S, Rajab N

Nutr Res, 2009 May;29(5):327-34.
PMID: 19555814 DOI: 10.1016/j.nutres.2009.05.006

The notion that dietary factors affect cognitive function and subsequently the risk of dementia has increased over the years from a global viewpoint. Because low folate intake has been described to impair cognitive function, we tested the hypothesis that low serum folate concentration is associated with cognitive impairment and an attenuated increase in DNA damage. We investigated the relationship between serum folate concentration, cognitive impairment, and DNA damage among elderly people attending health clinics in Klang Valley, an urban area in Malaysia. Two hundred thirty-two participants, composed of 115 men (49.6%) and 117 women (50.4%), were involved; none of the patients were diagnosed with neuropsychiatric problems, nor where they terminally ill. Sociodemography and health variables were assessed through face-to-face interview. Cognitive impairment review was conducted through an Elderly Cognitive Assessment Questionnaire. The estimation of dietary intake, serum folate concentration, and DNA damage was individually analyzed using validated Dietary History Questionnaires, immunoassay methods, and an Alkaline Comet Assay study (10 mL of peripheral venous blood), respectively. Results indicated that more men had cognitive impairment (33.0%) and DNA damage (27.0% for percentage DNA in tail, 22.6% tail moment) compared with women (25.6%, 15.4%, and 15.4%, respectively) (P < .05 for all parameters), recording an average folate deficiency value of 13.9% (0.2% higher than women). Multivariate binary logistic regression analysis outlined the association of cognitive impairment with older age (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.35-5.57), smoking habits (OR, 5.12; 95% CI, 2.48-10.57), poor serum folate concentration (OR, 3.46; 95% CI, 1.26-9.52), and DNA damage (percentage DNA in tail) (OR, 13.70; 95% CI, 1.36-138.29). In conclusion, this study highlighted the important role of serum folate concentration for cognitive function and provided a concise picture regarding the elevated levels of oxidative DNA damage in peripheral lymphocytes.
DNA Damage, Copper and Lead Associates with Cognitive Function among Older Adults

Meramat A, Rajab NF, Shahar S, Sharif RA

J Nutr Health Aging, 2017;21(5):539-545.
PMID: 28448084 DOI: 10.1007/s12603-016-0759-1

BACKGROUND: A cross sectional study was conducted in a group of 317 subjects older than 60 in Malaysia, aimed to determine risk factors associated with cognitive impairment in older adults, focusing on trace elements and DNA damage.
METHOD: Cognitive decline was determined by Montreal Cognitive Assessment (MoCA). Oxidative stress markers (malondialdehyde-MDA and superoxide dismutase-SOD) were determined and DNA damage was assayed using Alkaline Comet Assay. Toenail samples were taken and analyzed using ICP-MS to determine trace element levels.
RESULTS: A total of 62.1 % of subjects had cognitive impairment. Subjects with cognitive impairment had significantly higher levels of MDA and DNA damage as compared to the group with normal cognitive function; MDA (2.07 ± 0.05 nmol/L vs 1.85 ± 0.06 nmol/L) (p<0.05) and DNA damage (% Tail Density, 14.52 ± 0.32 vs 10.31 ± 0.42; Tail Moment, 1.79 ± 0.06 vs 1.28 ± 0.06) (p<0.05 for all parameters). However, the level of SOD among subjects with cognitive impairment (6.67 ± 0.33 u.e/min/mg protein) was lower than the level among those with normal cognitive functions (11.36 ± 0.65 u.e/min/mg protein) (p<0.05). Multiple logistic regression revealed the predictors for cognitive impairment among the subjects were DNA damage (Adjusted odd ratio [OR], 1.37; 95% confidence interval [CI], 1.18-1.59), level of trace elements in toenails namely, lead (OR, 2.471; CI, 1.535-3.980) and copper (OR, 1.275; CI, 1.047-1.552) (p<0.05).
CONCLUSION: High levels of lead and copper can lead to increase in oxidative stress levels and are associated with DNA damage that eventually could be associated with cognitive decline.
Toxicological evaluation of some Malaysian locally processed raw food products

Sharif R, Ghazali AR, Rajab NF, Haron H, Osman F

Food Chem Toxicol, 2008 Jan;46(1):368-74.
PMID: 17900779

Malaysian locally processed raw food products are widely used as main ingredients in local cooking. Previous studies showed that these food products have a positive correlation with the incidence of cancer. The cytotoxicity effect was evaluated using MTT assay (3-(4,5-dimetil-2-thiazolil)-2,5-diphenyl-2H-tetrazolium bromide) against Chang liver cells at 2000 microg/ml following 72 h incubation. Findings showed all methanol extracts caused a tremendous drop in the percentage of cell viability at 2000 microg/ml (shrimp paste - 41.69+/-3.36%, salted fish - 37.2+/-1.06%, dried shrimp - 40.32+/-1.8%, p<0.05). To detect DNA damage in a single cell, alkaline Comet Assay was used. None of the extracts caused DNA damage to the Chang liver cells at 62.5 microg/ml following 24 h incubation, as compared to the positive control, hydrogen peroxide (tail moment - 9.50+/-1.50; tail intensity - 30.50+/-2.50). Proximate analysis which was used for the evaluation of macronutrients in food showed that shrimp paste did not comply with the protein requirement (<25%) as in Food Act 1983. Salt was found in every sample with the highest percentage being detected in shrimp paste which exceeded 20%. Following heavy metal analysis (arsenic, cadmium, lead and mercury), arsenic was found in every sample with dried shrimps showing the highest value as compared to the other samples (6.16 mg/kg). In conclusion, several food extracts showed cytotoxic effect but did not cause DNA damage against Chang liver cells. Salt was found as the main additive and arsenic was present in every sample, which could be the probable cause of the toxicity effects observed.
Genetic, epigenetic, and lineage-directed mechanisms in benzene-induced malignancies and hematotoxicity targeting hematopoietic stem cells niche

Dewi R, Hamid ZA, Rajab NF, Shuib S, Razak SA

Hum Exp Toxicol, 2020 May;39(5):577-595.
PMID: 31884827 DOI: 10.1177/0960327119895570

Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.
Antioxidant Potential, DNA Damage, Inflammation, Glycemic Control and Lipid Metabolism Alteration: A Mediation Analysis of Islamic Sunnah Intermittent Fasting on Cognitive Function among Older Adults with Mild Cognitive Impairment

Ooi TC, Meramat A, Rajab NF, Shahar S, Sharif R

J Nutr Health Aging, 2022;26(3):272-281.
PMID: 35297471 DOI: 10.1007/s12603-022-1757-0

OBJECTIVES: This study aimed to determine the relationship between oxidative stress, DNA damage, inflammation, and metabolic biomarkers as the mediating factor between Islamic Sunnah intermittent fasting (IF) practice and cognitive function among older adults with mild cognitive impairment (MCI).
DESIGN: This study was a 36 months prospective cohort study.
SETTING: Community-dwelling older participants recruited through a stratified random sampling method from four states representing Malaysia's central, north-west, northeast and southern regions.
PARTICIPANTS: Ninety-nine Malay Muslim older adults (n= 99) aged 60 and above with MCI and no known critical illnesses were included in the current analysis. The participants were divided into regularly practicing IF (r-IF), irregularly practicing IF (i-IF) and not practicing IF (n-IF) groups.
MEASUREMENTS: Fasting venous blood was collected and used to determine the levels of oxidative stress, DNA damage, inflammatory and metabolic biomarkers. Mini-Mental State Examination, Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test, Digit Span and Digit symbol were used to evaluate the cognitive function. Then, the mediation analysis was conducted using a multistep regression model to determine the mediating role of various biomarkers between IF practice and cognitive function.
RESULTS: When comparing the r-IF and n-IF groups, higher SOD activity, lower DNA damage (percentage of DNA in tail), lower CRP levels and higher HDL-cholesterol levels established partial mediation while lower insulin levels established complete mediation between IF practice and better cognitive function. Meanwhile, when comparing the r-IF and i-IF groups, higher SOD activity and lower CRP levels completely mediated the effects of IF practice on better cognitive function.
CONCLUSION: It can be concluded that changes in antioxidant function, DNA damage, inflammation and a limited set of metabolic biomarkers (insulin and HDL cholesterol) may mediate improvements in cognitive function among older participants with MCI who practice Islamic Sunnah IF.
Cytotoxicity of triphenyltin(IV) methyl- and ethylisopropyldithiocarbamate compounds in chronic myelogenus leukemia cell line (K-562)

Awang N, Kamaludin NF, Hamid A, Mokhtar NW, Rajab NF

Pak J Biol Sci, 2012 Sep 01;15(17):833-8.
PMID: 24163967

Studies on the discovery of new cancer treatment by using metal-based compounds such as tin (Sn) has now greatly being synthesized and evaluated to identify their effectiveness and suitability to be developed as a new anticancer drug.
APPROACH: This study was carried out to evaluate the cytotoxicity of triphenyltin(lV) methylisopropyldithiocarbamate (compound 1) and triphenyltin(IV) ethylisopropyldithiocarbamate (compound (2) on chronic myelogenus leukemia cells. The determination of their cytotoxicity (IC50) at different time of exposure and concentration was carried out through the employment of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay.
RESULTS: The IC50 values obtained for compound 1 and 2 following treatment at 24, 48 and 72 h were 0.660, 0.223, 0.370 microM and 0.677, 0.306, 0.360 microM, respectively. Cell morphological changes such as apoptotic and necrotic features were also been observed.
CONCLUSION: The compounds tested were found to give cytotoxic effect against chronic myelogenus leukemia (K-562) cell at a micromolar dose. Thus, further study on their specific mechanism of actions in the human cells should be carried out to elucidate their potential as an anticancer agent.
Prevalence of gender disparities and predictors affecting the occurrence of mild cognitive impairment (MCI)

Lee LK, Shahar S, Chin AV, Mohd Yusoff NA, Rajab N, Aziz SA

Arch Gerontol Geriatr, 2012 Jan-Feb;54(1):185-91.
PMID: 21546098 DOI: 10.1016/j.archger.2011.03.015

The aims were to investigate the prevalence of mild cognitive impairment (MCI) within gender disparities in Malaysian older adults, and to determine the predictors of MCI according to gender disparities. A community-based sample of urban, multiethnic dwelling elderly aged 60 years of age and above from Cheras, Kuala Lumpur was recruited. Prevalence of all-type MCI, amnestic-type MCI (am-MCI) and non-amnestic-type MCI (nam-MCI) was assessed using comprehensive neuropsychological batteries. The association between demography, socioeconomic status, lifestyle practices, and nutritional status and health risk factors with MCI were examined. Predictors of MCI occurrence between gender disparities were determined. The prevalence of all-type MCI, am-MCI and nam-MCI was 21.1%, 15.4% and 5.7%, respectively. Binary logistic regression indicated that hypercholesterolemia is the significant predictor for MCI in men after adjustment for age, ethnicity and total years of education. While, in women, MCI was best predicted by married status, without exercise practice, overweight and obesity. These results suggest that approximately one-fifth of the studied elderly people had MCI. Predictors for MCI are totally different between men and women. It is critical to identify those at higher risk for MCI in order to implement preventative measures to delay or reverse this abnormal condition.
Fulltext Predictors' factors of nutritional status of male chronic obstructive pulmonary disease patients

Pirabbasi E, Najafiyan M, Cheraghi M, Shahar S, Abdul Manaf Z, Rajab N, et al.

ISRN Nurs, 2012;2012:782626.
PMID: 23209935 DOI: 10.5402/2012/782626

Chronic obstructive pulmonary disease (COPD) is a systemic disease that leads to weight loss and muscle dysfunction resulting in an increase in mortality. This study aimed to determine the prevalence rate of malnutrition and nutritional status and also factors associated with nutritional status. A total of 149 subjects were involved in the cross-sectional study. The study was conducted at two medical centers in Kuala Lumpur, Malaysia. The results of the study showed that malnutrition was more prevalent (52.4%) in the subjects with severe stages of COPD as compared to mild and moderate COPD stages (26.2%) (P < 0.05). Fat-free mass depletion as assessed using fat-free mass index (FFMI) affected 41.9% of the subjects. Plasma vitamin A, peak expiratory flow (PEF), and handgrip were the predictors for body mass index (BMI) (R(2) = 0.190, P < 0.001). Plasma vitamin A and force expiratory volume in one second (FEV(1)) were the predictors of FFMI (R(2) = 0.082, P = 0.007). BMI was the predictor of respiratory factors, that is, FEV(1)% predicted (R(2) = 0.052, P = 0.011). It can be concluded that there is a need to identify malnourished COPD patients for an appropriate nutrition intervention.
Study site: outpatient clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Institute of Respiratory Medicine
Cell death induced by hydroxyapatite on L929 fibroblast cells

Inayat-Hussain SH, Rajab NF, Roslie H, Hussin AA, Ali AM, Annuar BO

Med J Malaysia, 2004 May;59 Suppl B:176-7.
PMID: 15468875

Biomaterials intended for end-use application as bone-graft substitutes have to undergo safety evaluation. In this study, we investigated the in vitro cytotoxic effects especially to determine the mode of death of two hydroxyapatite compounds (HA2, HA3) which were synthesized locally. The methods used for cytotoxicity was the standard MTT assay whereas AO/PI staining was performed to determine the mode of cell death in HA treated L929 fibroblasts. Our results demonstrated that both HA2 and HA3 were not significantly cytotoxic as more than 75% cells after 72 hours treatment were viable. Furthermore, we found that the major mode of cell death in HA treated cells was apoptosis. In conclusion, our results demonstrated that these hydroxyapatite compounds are not cytotoxic where the mode of death was primarily via apoptosis.
DNA damage evaluation of hydroxyapatite on fibroblast cell L929 using the single cell gel electrophoresis assay

Rajab NF, Yaakob TA, Ong BY, Hamid M, Ali AM, Annuar BO, et al.

Med J Malaysia, 2004 May;59 Suppl B:170-1.
PMID: 15468872

Hydroxyapatite is the main component of the bone which is a potential biomaterial substance that can be applied in orthopaedics. In this study, the biocompatibility of this biomaterial was assessed using an in vitro technique. The cytotoxicity and genotoxicity effect of HA2 and HA3 against L929 fibroblast cell was evaluated using the MTT Assay and Alkaline Comet Assay respectively. Both HA2 and HA3 compound showed low cytotoxicity effect as determined using MTT Assay. Cells viability following 72 hours incubation at maximum concentration of both HA2 and HA3 (200 mg/ml) were 75.3 +/- 8.8% and 86.7 +/- 13.1% respectively. However, the cytotoxicity effect of ZnSO4.7H2O as a positive control showed an IC50 values of 46 mg/ml (160 microM). On the other hand, both HA2 and HA3 compound showed a slight genotoxicity effect as determined using the Alkaline Comet Assay following incubation at the concentration 200 mg/ml for 72 hours. This assay has been widely used in genetic toxicology to detect DNA strand breaks and alkali-labile site. The percentage of the cells with DNA damage for both substance was 27.7 +/- 1.3% and 15.6 +/- 1.0% for HA2 and HA3 respectively. Incubation of the cells for 24 hours with 38 microg/ml (IC25) of positive control showed an increase in percentage of cells with DNA damage (67.5 +/- 0.7%). In conclusion, our study indicated that both hydroxyapatite compounds showed a good biocompatibility in fibroblast cells.
Fulltext What are the antioxidant status predictors' factors among male chronic obstructive pulmonary disease (COPD) patients?

Pirabbasi E, Najafiyan M, Cheraghi M, Shahar S, Abdul Manaf Z, Rajab N, et al.

Glob J Health Sci, 2013 Jan;5(1):70-8.
PMID: 23283038 DOI: 10.5539/gjhs.v5n1p70

Imbalance between antioxidant and oxidative stress is a major risk factor for pathogenesis of some chronic diseases such as chronic obstructive pulmonary disease (COPD). This study aimed to determine antioxidant and oxidative stress status, and also theirs association with respiratory function of male COPD patients to find the antioxidant predictors' factors. A total of 149 subjects were involved in a cross-sectional study. The study was conducted at two medical centers in Kuala Lumpur, Malaysia. Results of the study showed that plasma vitamin C was low in most of the subjects (86.6%). Total antioxidant capacity was the lowest in COPD stage IV compare to other stages (p < 0.05). Level of plasma vitamin A (p= 0.012) and vitamin C (p= 0.007) were low in malnourished subjects. The predictors for total antioxidant capacity were forced vital capacity (FVC) % predicted and intake of ?-carotene (R2= 0.104, p= 0.002). Number of cigarette (pack/ year) and smoking index (number/ year) were not associated with total antioxidant capacity of this COPD population. Plasma oxidative stress as assessed plasma lipid peroxidation (LPO) was only positively correlated with plasma glutathione (p= 0.002). It might be a need to evaluate antioxidant status especially in older COPD patients to treat antioxidant deficiency which is leading to prevent COPD progression.
Study site: Outpatient clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM) and Institute of Respiratory Medicine, Kuala Lumpur, Malaysia
The role of long chain omega-3 polyunsaturated fatty acids in reducing lipid peroxidation among elderly patients with mild cognitive impairment: a case-control study

Lee LK, Shahar S, Rajab N, Yusoff NA, Jamal RA, Then SM

J Nutr Biochem, 2013 May;24(5):803-8.
PMID: 22898566 DOI: 10.1016/j.jnutbio.2012.04.014

The present work explores the effect of dietary omega-3 polyunsaturated fatty acids (PUFAs) intake on lipid peroxidation among mild cognitive impairment (MCI) patients. The plasma lipid hydroperoxide (LPO) levels in 67 MCI patients were compared to those of 134 healthy elderly controls. Omega-3 PUFA intake was assessed using an interviewer-administered food frequency questionnaire. Apolipoprotein E genotyping was performed using polymerase chain reaction and restriction enzyme digestion. The association between various confounders and lipid peroxidation was evaluated using regression analysis. The influence of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intake on LPO level was investigated. The results revealed that LPO levels were significantly higher in the MCI group than in the control group. Inverse correlations were found between DHA and EPA intake and LPO level among the MCI group. LPO levels decreased significantly with increasing DHA and EPA intake. In summary, the findings revealed that DHA and EPA can play a role in alleviating oxidative stress and reducing the risk of neurodegenerative diseases.
Modulation of the benzene metabolite hydroquinone induced toxicity: evidence for an important role of fau

Inayat-Hussain SH, Ibrahim HA, Siew EL, Rajab NF, Chan KM, G T Williams, et al.

Chem Biol Interact, 2010 Mar 19;184(1-2):310-2.
PMID: 20025857 DOI: 10.1016/j.cbi.2009.12.009
Goniothalamin induces apoptosis in vascular smooth muscle cells

Chan KM, Rajab NF, Ishak MH, Ali AM, Yusoff K, Din LB, et al.

Chem Biol Interact, 2006 Feb 1;159(2):129-40.
PMID: 16297902

Restenosis represents a major impediment to the success of coronary angioplasty. Abnormal proliferation of vascular smooth muscle cells (VSMCs) has been shown to be an important process in the pathogenesis of restenosis. A number of agents, particularly rapamycin and paclitaxel, have been shown to impact on this process. This study was carried out to determine the mechanisms of cytotoxicity of goniothalamin (GN) on VSMCs. Results from MTT cytotoxicity assay showed that the IC(50) for GN was 4.4 microg/ml (22 microM), which was lower compared to the clinically used rapamycin (IC(50) of 25 microg/ml [27.346 microM]). This was achieved primarily via apoptosis where up to 25.83 +/- 0.44% of apoptotic cells were detected after 72 h treatment with GN. In addition, GN demonstrated similar effects as rapamycin in inhibiting VSMCs proliferation using bromodeoxyuridine (BrdU) cell proliferation assay after 72 h treatment at IC(50) concentration (p > 0.05). In order to understand the mechanisms of GN, DNA damage detection using comet assay was determined at 2h post-treatment with GN. Our results showed that there was a concentration-dependent increase in DNA damage in VSMCs prior to cytotoxicity. Moreover, GN effects were comparable to rapamycin. In conclusion, our data show that GN initially induces DNA damage which subsequently leads to cytotoxicity primarily via apoptosis in VSMCs.
Fulltext Goniothalamin-induced oxidative stress, DNA damage and apoptosis via caspase-2 independent and Bcl-2 independent pathways in Jurkat T-cells

Inayat-Hussain SH, Chan KM, Rajab NF, Din LB, Chow SC, Kizilors A, et al.

Toxicol Lett, 2010 Mar 1;193(1):108-14.
PMID: 20026395 DOI: 10.1016/j.toxlet.2009.12.010

Goniothalamin (GTN) isolated from Goniothalamus sp. has been demonstrated to induce apoptosis in a variety of cancer cell lines including Jurkat T leukemia cells. However, the mechanism of GTN-induced apoptosis upstream of mitochondria is still poorly defined. In this study, GTN caused a decrease in GSH with an elevation of reactive oxygen species as early as 30 min and DNA damage as assessed by Comet assay. Analysis using topoisomerase II processing of supercoiled pBR 322 DNA showed that GTN caused DNA damage via a topoisomerase II-independent pathway suggesting that cellular oxidative stress may contribute to genotoxicity. A 12-fold increase of caspase-2 activity was observed in GTN-treated Jurkat cells after 4h treatment and this was confirmed using Western blotting. Although the caspase-2 inhibitor Z-VDVAD-FMK inhibited the proteolytic activity of caspase-2, apoptosis ensued confirming that caspase-2 activity was not crucial for GTN-induced apoptosis. However, GTN-induced apoptosis was completely abrogated by N-acetylcysteine further confirming the role of oxidative stress. Since cytochrome c release was observed as early as 1h without any appreciable change in Bcl-2 protein expression, we further investigated whether overexpression of Bcl-2 confers resistance in GTN-induced cytotoxicity. Using a panel of Jurkat Bcl-2 transfectants, GTN cytotoxicity was not abrogated in these cells. In conclusion, GTN induces DNA damage and oxidative stress resulting in apoptosis which is independent of both caspase-2 and Bcl-2.
Association between vitamin A, vitamin E and apolipoprotein E status with mild cognitive impairment among elderly people in low-cost residential areas

Shahar S, Lee LK, Rajab N, Lim CL, Harun NA, Noh MF, et al.

Nutr Neurosci, 2013 Jan;16(1):6-12.
PMID: 23321337 DOI: 10.1179/1476830512Y.0000000013

The influence of nutritional parameters and genetic susceptibility on poor cognitive impairment has been documented; however, the association between lipid-soluble vitamins with genetic susceptibility on mild cognitive impairment (MCI) has not yet been studied extensively.
Fulltext RACK-1 overexpression protects against goniothalamin-induced cell death

Inayat-Hussain SH, Wong LT, Chan KM, Rajab NF, Din LB, Harun R, et al.

Toxicol Lett, 2009 Dec 15;191(2-3):118-22.
PMID: 19698770 DOI: 10.1016/j.toxlet.2009.08.012

Goniothalamin, a styryllactone, has been shown to induce cytotoxicity via apoptosis in several tumor cell lines. In this study, we have examined the potential role of several genes, which were stably transfected into T-cell lines and which regulate apoptosis in different ways, on goniothalamin-induced cell death. Overexpression of full-length receptor for activated protein C-kinase 1 (RACK-1) and pc3n3, which up-regulates endogenous RACK-1, in both Jurkat and W7.2 T cells resulted in inhibition of goniothalamin-induced cell death as assessed by MTT and clonogenic assays. However, overexpression of rFau (antisense sequence to Finkel-Biskis-Reilly murine sarcoma virus-associated ubiquitously expressed gene) in W7.2 cells did not confer resistance to goniothalamin-induced cell death. Etoposide, a clinically used cytotoxic agent, was equipotent in causing cytotoxicity in all the stable transfectants. Assessment of DNA damage by Comet assay revealed goniothalamin-induced DNA strand breaks as early as 1 h in vector control but this effect was inhibited in RACK-1 and pc3n3 stably transfected W7.2 cells. This data demonstrate that RACK-1 plays a crucial role in regulating cell death signalling pathways induced by goniothalamin.

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links