Displaying publications 21 - 40 of 105 in total

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  1. Mai CW, Kang YB, Nadarajah VD, Hamzah AS, Pichika MR
    Phytother Res, 2018 Jun;32(6):1108-1118.
    PMID: 29464796 DOI: 10.1002/ptr.6051
    In this study, a series of 20 structurally similar vanilloids (Vn) were tested for their antiproliferative effects against 12 human cancer cells: human breast (MCF-7 and MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29 and HCT116), nasopharyngeal (CNE-1 and HK-1), and leukemic (K562 and CEM-SS) cancer cells. Among all the tested vanilloids, Vn16 (6-shogaol) exhibited the most potent cytotoxic effects against human colorectal cancer cells (HT-29). The apoptotic induction effects exhibited by Vn16 on HT-29 cells were confirmed using dual staining fluorescence microscopy and enzyme-linked immunosorbent assay. The effects of Vn16 on regulation of 43 apoptotic-related markers were determined in HT-29. The results suggested that 8 apoptotic markers (caspase 8, BAD, BAX, second mitochondrial-derived activator, caspase 3, survivin, bcl-2, and cIAP-2) were either upregulated or downregulated. These results further support the chemopreventive properties of foods that contain vanilloids.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/metabolism*
  2. Abdullah H, Ismail I, Suppian R, Zakaria NM
    Int J Mol Sci, 2023 May 09;24(10).
    PMID: 37239840 DOI: 10.3390/ijms24108495
    Induction of apoptosis is one of the targeted approaches in cancer therapies. As previously reported, natural products can induce apoptosis in in vitro cancer treatments. However, the underlying mechanisms of cancer cell death are poorly understood. The present study aimed to elucidate cell death mechanisms of gallic acid (GA) and methyl gallate (MG) from Quercus infectoria toward human cervical cancer cell lines (HeLa). The antiproliferative activity of GA and MG was characterised by an inhibitory concentration using 50% cell populations (IC50) by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Cervical cancer cells, HeLa, were treated with GA and MG for 72 h and calculated for IC50 values. The IC50 concentration of both compounds was used to elucidate the apoptotic mechanism using acridine orange/propidium iodide (AO/PI) staining, cell cycle analysis, the Annexin-V FITC dual staining assay, apoptotic proteins expressions (p53, Bax and Bcl-2) and caspase activation analysis. GA and MG inhibited the growth of HeLa cells with an IC50 value of 10.00 ± 0.67 µg/mL and 11.00 ± 0.58 µg/mL, respectively. AO/PI staining revealed incremental apoptotic cells. Cell cycle analysis revealed an accumulation of cells at the sub-G1 phase. The Annexin-V FITC assay showed that cell populations shifted from the viable to apoptotic quadrant. Moreover, p53 and Bax were upregulated, whereas Bcl-2 was markedly downregulated. Activation of caspase 8 and 9 showed an ultimate apoptotic event in HeLa cells treated with GA and MG. In conclusion, GA and MG significantly inhibited HeLa cell growth through apoptosis induction by the activation of the cell death mechanism via extrinsic and extrinsic pathways.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/metabolism
  3. Mohamad Rosdi MN, Mohd Arif S, Abu Bakar MH, Razali SA, Mohamed Zulkifli R, Ya'akob H
    Apoptosis, 2018 01;23(1):27-40.
    PMID: 29204721 DOI: 10.1007/s10495-017-1434-7
    Annona muricata Linn or usually identified as soursop is a potential anticancer plant that has been widely reported to contain valuable chemopreventive agents known as annonaceous acetogenins. The antiproliferative and anticancer activities of this tropical and subtropical plant have been demonstrated in cell culture and animal studies. A. muricata L. exerts inhibition against numerous types of cancer cells, involving multiple mechanism of actions such as apoptosis, a programmed cell death that are mainly regulated by Bcl-2 family of proteins. Nonetheless, the binding mode and the molecular interactions of the plant's bioactive constituents have not yet been unveiled for most of these mechanisms. In the current study, we aim to elucidate the binding interaction of ten bioactive phytochemicals of A. muricata L. to three Bcl-2 family of antiapoptotic proteins viz. Bcl-2, Bcl-w and Mcl-1 using an in silico molecular docking analysis software, Autodock 4.2. The stability of the complex with highest affinity was evaluated using MD simulation. We compared the docking analysis of these substances with pre-clinical Bcl-2 inhibitor namely obatoclax. The study identified the potential chemopreventive agent among the bioactive compounds. We also characterized the important interacting residues of protein targets which involve in the binding interaction. Results displayed that anonaine, a benzylisoquinoline alkaloid, showed a high affinity towards the Bcl-2, thus indicating that this compound is a potent inhibitor of the Bcl-2 antiapoptotic family of proteins.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors*; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; Proto-Oncogene Proteins c-bcl-2/chemistry
  4. Mohana-Kumaran N, Hill DS, Allen JD, Haass NK
    Pigment Cell Melanoma Res, 2014 Jul;27(4):525-39.
    PMID: 24655414 DOI: 10.1111/pcmr.12242
    Melanoma drug resistance is often attributed to abrogation of the intrinsic apoptosis pathway. Targeting regulators of apoptosis is thus considered a promising approach to sensitizing melanomas to treatment. The development of small-molecule inhibitors that mimic natural antagonists of either antiapoptotic members of the BCL-2 family or the inhibitor of apoptosis proteins (IAPs), known as BH3- or SMAC-mimetics, respectively, are helping us to understand the mechanisms behind apoptotic resistance. Studies using BH3-mimetics indicate that the antiapoptotic BCL-2 protein MCL-1 and its antagonist NOXA are particularly important regulators of BCL-2 family signaling, while SMAC-mimetic studies show that both XIAP and the cIAPs must be targeted to effectively induce apoptosis of cancer cells. Although most solid tumors, including melanoma, are insensitive to these mimetic drugs as single agents, combinations with other therapeutics have yielded promising results, and tests combining them with BRAF-inhibitors, which have already revolutionized melanoma treatment, are a clear priority.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/metabolism; Proto-Oncogene Proteins c-bcl-2/chemistry*
  5. Al-Qubaisi MS, Rasedee A, Flaifel MH, Ahmad SH, Hussein-Al-Ali S, Hussein MZ, et al.
    Int J Nanomedicine, 2013;8:4115-29.
    PMID: 24204141 DOI: 10.2147/IJN.S50061
    The long-term objective of the present study was to determine the ability of NiZn ferrite nanoparticles to kill cancer cells. NiZn ferrite nanoparticle suspensions were found to have an average hydrodynamic diameter, polydispersity index, and zeta potential of 254.2 ± 29.8 nm, 0.524 ± 0.013, and -60 ± 14 mV, respectively. We showed that NiZn ferrite nanoparticles had selective toxicity towards MCF-7, HepG2, and HT29 cells, with a lesser effect on normal MCF 10A cells. The quantity of Bcl-2, Bax, p53, and cytochrome C in the cell lines mentioned above was determined by colorimetric methods in order to clarify the mechanism of action of NiZn ferrite nanoparticles in the killing of cancer cells. Our results indicate that NiZn ferrite nanoparticles promote apoptosis in cancer cells via caspase-3 and caspase-9, downregulation of Bcl-2, and upregulation of Bax and p53, with cytochrome C translocation. There was a concomitant collapse of the mitochondrial membrane potential in these cancer cells when treated with NiZn ferrite nanoparticles. This study shows that NiZn ferrite nanoparticles induce glutathione depletion in cancer cells, which results in increased production of reactive oxygen species and eventually, death of cancer cells.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/analysis; Proto-Oncogene Proteins c-bcl-2/metabolism
  6. Looi CY, Moharram B, Paydar M, Wong YL, Leong KH, Mohamad K, et al.
    PMID: 23837445 DOI: 10.1186/1472-6882-13-166
    Centratherum anthelminticum (L.) Kuntze (scientific synonyms: Vernonia anthelmintica; black cumin) is one of the ingredients of an Ayurvedic preparation, called "Kayakalp", commonly applied to treat skin disorders in India and Southeast Asia. Despite its well known anti-inflammatory property on skin diseases, the anti-cancer effect of C. anthelminticum seeds on skin cancer is less documented. The present study aims to investigate the anti-cancer effect of Centratherum anthelminticum (L.) seeds chloroform fraction (CACF) on human melanoma cells and to elucidate the molecular mechanism involved.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism*
  7. Ng WK, Yazan LS, Ismail M
    Toxicol In Vitro, 2011 Oct;25(7):1392-8.
    PMID: 21609759 DOI: 10.1016/j.tiv.2011.04.030
    Thymoquinone (TQ), the active constituent of Nigella sativa or black cumin exhibited cytotoxic effects in several cancer cell lines. In this study, the cytotoxicity of TQ in human cervical squamous carcinoma cells (SiHa) was investigated. TQ was cytotoxic towards SiHa cells with IC50 values of 10.67 ± 0.12 and 9.33 ± 0.19 μg/mL as determined by MTT assay and trypan blue dye exclusion test, respectively, after 72 h of incubation. TQ was more cytotoxic towards SiHa cells compared to cisplatin. Interestingly, TQ was less cytotoxic towards the normal cells (3T3-L1 and Vero). Cell cycle analysis performed by flowcytometer showed a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Apoptosis induction by TQ was further confirmed by Annexin V/PI and AO/PI staining. Significant elevation of p53 and down-regulation of the anti-apoptotic Bcl-2 protein was found in the treated cells, without any changes in the expression of the pro-apoptotic Bax protein. In conclusion, thymoquinone from N. sativa was more potent than cisplatin in elimination of SiHa cells via apoptosis with down-regulation of Bcl-2 protein.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism*
  8. 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.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/metabolism; Proto-Oncogene Proteins c-bcl-2/physiology*
  9. Abdulamir AS, Kadhim HS, Hafidh RR, Ali MA, Faik I, Abubakar F, et al.
    PMID: 19610265
    OBJECTIVES: We studied the role of the regulatory T cells CD4+CD25+ (Treg) and activated CD4+CD30+ cells in the pathogenesis of asthma and their association with apoptosis and NF-kappaB in patients with mild intermittent asthma (MA), severe persistent asthma (SA), and healthy volunteers (HV).
    METHODS: Peripheral blood lymphocytes (PBL) were extracted from asthmatic patients during exacerbations, and CD4+ cells were separated using Dynal beads. Immunostaining of whole PBL for NF-kappaB, Bax, and Bcl-2, and immunostaining of CD4+ cells for CD25+ and CD30+ cells were performed using immunocytochemistry.
    RESULTS: Treg cells were expressed at higher levels in MA than in HV and SA (P < .05), while CD30+ T cells were expressed at higher levels in both SA and MA than in HV (P < .05), although there was no remarkable difference between SA and MA (P>.05). Levels of NF-kappaB, Bcl-2, and Bcl-2/Bax increased, whereas those of Bax decreased, progressively, from MA to SA (P < .05). NF-kappaB levels correlated directly with the Bcl-2/Bax ratio and with CD4+CD30+ cells in SA and MA, whereas CD4+CD30+ cells correlated inversely with the Bcl-2/Bax ratio.
    CONCLUSIONS: Unregulated Treg cells probably return inflammatory responses to normal values during exacerbations in MA; however, expression of Treg cells was extensively diminished in SA, leading to probable loss of suppressive control over underlying immune reactions. CD4+CD30+ cells were associated with the pathogenesis of asthma but not with severity. NF-kappaB seems to be the central inflammatory factor in SA, with a remarkable loss of PBL apoptosis, diminished Treg levels, and high CD30+ cell levels that probably induce NF-kappaB, which in turn blocks the proapoptotic potential of CD30 induction itself.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/immunology; Proto-Oncogene Proteins c-bcl-2/metabolism
  10. Peh SC, Shaminie J, Tai YC, Tan J, Gan SS
    Histopathology, 2004 Nov;45(5):501-10.
    PMID: 15500654
    Follicular lymphoma is frequently associated with t(14;18)(q32;q21) translocation. This study was undertaken to determine the pattern of Bcl-2, CD10 and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi-ethnic Asian population.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism
  11. Hii LW, Lim SE, Leong CO, Chin SY, Tan NP, Lai KS, et al.
    BMC Complement Altern Med, 2019 Sep 14;19(1):257.
    PMID: 31521140 DOI: 10.1186/s12906-019-2663-9
    BACKGROUND: Clinacanthus nutans extracts have been consumed by the cancer patients with the hope that the extracts can kill cancers more effectively than conventional chemotherapies. Our previous study reported its anti-inflammatory effects were caused by inhibiting Toll-like Receptor-4 (TLR-4) activation. However, we are unsure of its anticancer effect, and its interaction with existing chemotherapy.

    METHODS: We investigated the anti-proliferative efficacy of polar leaf extracts (LP), non-polar leaf extracts (LN), polar stem extract (SP) and non-polar stem extracts (SN) in human breast, colorectal, lung, endometrial, nasopharyngeal, and pancreatic cancer cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT assay. The most potent extracts was tested along with gemcitabine using our established drug combination analysis. The effect of the combinatory treatment in apoptosis were quantified using enzyme-linked immunosorbent assay (ELISA), Annexin V assay, antibody array and immunoblotting. Statistical significance was analysed using one-way analysis of variance (ANOVA) and post hoc Dunnett's test. A p-value of less than 0.05 (p C. nutans SN extracts acting in synergy with gemcitabine, the first line chemotherapy for pancreatic cancer, as compared to conventional monotherapy. In the presence of SN extracts, we can reduce the dose of gemcitabine 2.38-5.28 folds but still maintain the effects of gemcitabine in PDAC. SN extracts potentiated the killing of gemcitabine in PDAC by apoptosis. Bax was upregulated while bcl-2, cIAP-2, and XIAP levels were downregulated in SW1990 and BxPC3 cells treated with gemcitabine and SN extracts. The synergism was independent of TLR-4 expression in pancreatic cancer cells.

    CONCLUSION: These results provide strong evidence of C. nutans extracts being inefficacious as monotherapy for cancer. Hence, it should not be used as a total substitution for any chemotherapy agents. However, SN extracts may synergise with gemcitabine in the anti-tumor mechanism.

    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism
  12. Gao X, Yanan J, Santhanam RK, Wang Y, Lu Y, Zhang M, et al.
    J Food Sci, 2021 Feb;86(2):366-375.
    PMID: 33448034 DOI: 10.1111/1750-3841.15599
    Liver damage is a common liver disorder, which could induce liver cancer. Oral antioxidant is one of the effective treatments to prevent and alleviate liver damage. In this study, three flavonoids namely myricetin, isoquercitrin, and isorhamnetin were isolated and identified from Laba garlic. The isolated compounds were investigated on the protective effects against H2 O2 -induced oxidative damages in hepatic L02 cells and apoptosis inducing mechanism in hepatic cancer cells HepG2 by using MTT assay, flow cytometry and western blotting analysis. Myricetin, isoquercitrin, and isorhamnetin showed proliferation inhibition on HepG2 cells with IC50 value of 44.32 ± 0.213 µM, 49.68 ± 0.192 µM, and 54.32 ± 0.176 µM, respectively. While they showed low toxicity on normal cell lines L02. They could significantly alleviate the oxidative damage towards L02 cells (P < 0.05), via inhibiting the morphological changes in mitochondria and upholding the integrity of mitochondrial structure and function. The fluorescence intensity of L02 cells pre-treated with myricetin, isoquercitrin, and isorhamnetin (100 µM) was 89.23 ± 1.26%, 89.35 ± 1.43% and 88.97 ± 0.79%, respectively. Moreover, the flavonoids could induce apoptosis in HepG2 cells via Bcl-2/Caspase pathways, where it could up-regulate the expression of Bax and down-regulate the expression of Bcl-2, Bcl-xL, pro-Caspase-3, and pro-Caspase-9 proteins in a dose dependent manner. Overall, the results suggested that the flavonoids from Laba garlic might be a promising candidate for the treatment of various liver disorders. PRACTICAL APPLICATION: Flavonoids from Laba garlic showed selective toxicity towards HepG2 cells in comparison to L02 cells via regulating Bcl-2/caspase pathway. Additionally, the isolated flavonoids expressively barred the oxidative damage induced by H2 O2 in L02 cells. These results suggested that the flavonoids from laba garlic could be a promising agent towards the development of functional foods.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism*
  13. Masir N, Campbell LJ, Jones M, Mason DY
    Pathology, 2010 Apr;42(3):212-6.
    PMID: 20350212 DOI: 10.3109/00313021003631296
    The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein expression in most follicular lymphomas. However, a small number of cases lack BCL2 expression despite carrying the t(14;18)(q32;q21) translocation. This study aims to explore the mechanism accounting for the lack of BCL2 protein expression when the t(14;18) translocation is present.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/genetics*; Proto-Oncogene Proteins c-bcl-2/immunology*
  14. Ibrahim N, Nazimi AJ, Ajura AJ, Nordin R, Latiff ZA, Ramli R
    J Craniofac Surg, 2016 Jul;27(5):1361-6.
    PMID: 27391504 DOI: 10.1097/SCS.0000000000002792
    The aim of this study was to describe the clinical features and expression of bcl-2, cyclin D1, p53, and proliferating cell nuclear antigen (PCNA) antibodies in syndromic (nevoid basal cell carcinoma syndrome [NBCCS]) and nonsyndromic patients diagnosed with keratocystic odontogenic tumor (KCOT).

    METHODS: This descriptive study comprised 5 patients of KCOT associated with NBCCS and 8 patients of nonsyndromic type treated in the Department of Oral Maxillofacial Surgery, Universiti Kebangsaan Malaysia Medical Centre between years 1998 and 2011. The clinical features (site, size, treatment, and recurrence), demographic characteristics, and immunohistochemistry results using antibodies of bcl-2, cyclin D1, p53, and PCNA were examined. The association of the antibody expression and the type of KCOT was analyzed using Fisher exact test.

    RESULTS: Altogether there were 13 patients, 5 with syndromic KCOT (1 patient met 3 major criteria of NBCCS) and 8 with sporadic KCOT. The age range for syndromic KCT was 11 to 21 years (mean 16.00 years, SD 4.36) and 10 to 54 years (median 24.50 years, interquartile range 19.00) for the nonsyndromic KCOT. Tumor recurrence occurred in 3 patients (7.7%); 1 patient from the syndromic and 2 patients from the nonsyndromic. The most positive expression was observed in PCNA for both the syndromic and nonsyndromic samples and the least positive expression involved the p53.

    CONCLUSION: PCNA, bcl-2 protein, and cyclin D1 expressions could be useful in evaluating the proliferative activity of the tumor and the aggressiveness of the clinical presentation; however, the authors would propose for larger sample size research for more definitive results.

    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/biosynthesis; Proto-Oncogene Proteins c-bcl-2/genetics*
  15. Shanmugapriya, Chen Y, Kanwar JR, Sasidharan S
    Nutr Cancer, 2017 10 25;69(8):1308-1324.
    PMID: 29068745 DOI: 10.1080/01635581.2017.1367944
    This study was conducted to investigate the anticancer effects and mechanism of Calophyllum inophyllum fruit extract against MCF-7 cells. C. inophyllum fruit extract was found to have markedly cytotoxic effect against MCF-7 cells in a dose-dependent manner with the IC50 for 24 h of 23.59 µg/mL. Flow cytometry analysis revealed that C. inophyllum fruit extract mediated cell cycle at G0/G1 and G2/M phases, and MCF-7 cells entered the early phase of apoptosis. The expression of anti-apoptotic proteins Bcl-2 was decreased whereas the expression of the pro-apoptotic protein Bax, cytochrome C and p53 were increased after treatment. C. inophyllum fruit extract led to apoptosis in MCF-7 cells via the mitochondrial pathway in a dose dependent manner. This is evidenced by the elevation of intracellular ROS, the loss of mitochondria membrane potential (Δψm), and activation of caspase-3. Meanwhile, dose-dependent genomic DNA fragmentation was observed after C. inophyllum fruits extract treatment by comet assay. This study shows that C. inophyllum fruits extract-induced apoptosis is primarily p53 dependent and mediated through the activation of caspase-3. C. inophyllum fruit extract could be an excellent source of chemopreventive agent in the treatment of breast cancer and has potential to be explored as green anticancer agent.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism
  16. Chiroma SM, Baharuldin MTH, Mat Taib CN, Amom Z, Jagadeesan S, Ilham Adenan M, et al.
    Int J Mol Sci, 2019 Apr 16;20(8).
    PMID: 31014012 DOI: 10.3390/ijms20081871
    Alzheimer's disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aβ) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl3) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl3 induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3β). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat's hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl3 induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism
  17. Lian BSX, Yek AEH, Shuvas H, Abdul Rahman SF, Muniandy K, Mohana-Kumaran N
    BMC Res Notes, 2018 Mar 27;11(1):197.
    PMID: 29580266 DOI: 10.1186/s13104-018-3302-0
    OBJECTIVE: There are number of studies which report that BCL-2 anti-apoptotic proteins (e.g. BCL-2, BCL-XL, and MCL-1) are highly expressed in cervical cancer tissues compared to the normal cervical epithelia. Despite these reports, targeting these proteins for cervical cancer treatment has not been explored extensively. BH3-mimetics that inhibit specific BCL-2 anti-apoptotic proteins may hold encouraging treatment outcomes for cervical cancer management. Hence, the aim of this pilot study is to investigate the sensitivity of cervical cancer cell lines to combination of two BH3-mimetics namely ABT-263 which selectively inhibits BCL-2, BCL-XL and BCL-w and A-1210477, a selective MCL-1 inhibitor.

    RESULTS: We report that combination of A-1210477 and ABT-263 exhibited synergistic effects on all cervical cancer cell lines tested. Drug sensitization studies revealed that A-1210477 sensitised the cervical cancer cell lines SiHa and CaSki to ABT-263 by 11- and fivefold, respectively. Sensitization also occurred in the opposite direction whereby ABT-263 sensitised SiHa and CaSki to A-1210477 by eightfold. This report shows that combination of ABT-263 and A-1210477 could be a potential treatment strategy for cervical cancer. Extensive drug mechanistic studies and drug sensitivity studies in physiological models are necessary to unleash the prospect of this combination for cervical cancer therapy.

    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2/metabolism
  18. Khodapasand E, Jafarzadeh N, Farrokhi F, Kamalidehghan B, Houshmand M
    Iran Biomed J, 2015;19(2):69-75.
    PMID: 25864810
    BACKGROUND: Bax and Bcl-2 are the major members of Bcl-2 family whose play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction. Therefore, the balance between pro- and anti-apoptotic members of this family can determine the cellular fate.

    METHODS: In this study, the relative level of mRNA expression of Bax and Bcl-2 genes was determined using RNA extraction, cDNA synthesis and RT-qPCR technique from 22 tumoral tissues and adjacent non-tumoral tissues from adenocarcinoma colorectal cancer.

    RESULTS: The potential prognostic and predictive significance of Bax and Bcl-2 gene expression and Bax/Bcl-2 ratio were demonstrated in colorectal cancer. The significant correlation between qPCR data and different clinicopathologic parameters of colorectal carcinoma, including age, gender, tumor size, tumor stage, tumor location, and tumor differentiation was also examined. Interestingly, no significant correlation was seen between Bax and Bcl-2 expressions and clinicopathological parameters of colorectal cancer. However, Bax/Bcl-2 ratio was statistically correlated with age and tumor location. Patients with age above 50 showed decreased levels of Bax/Bcl-2 ratio. Moreover, the Bax/Bcl-2 ratio was significantly lower in tumors resected from colon compared to sigmoid colon, rectosigmoid and rectum tumors.

    CONCLUSION: This study indicates a significant correlation between age and tumor location with Bax/Bcl-2 expression ratio, suggesting predictive value as a potential molecular marker of colorectal cancer.

    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/genetics*; Proto-Oncogene Proteins c-bcl-2/metabolism
  19. Abdulamir AS, Hafidh RR, Bakar FA
    Mol. Cancer, 2010;9:249.
    PMID: 20846456 DOI: 10.1186/1476-4598-9-249
    Colorectal cancer (CRC) has long been associated with bacteremia and/or endocarditis by Streptococcus gallolyticus member bacteria (SGMB) but the direct colonization of SGMB along with its molecular carcinogenic role, if any, has not been investigated. We assessed the colonization of SGMB in CRC patients with history of bacteremia (CRC-w/bac) and without history of bacteremia (CRC-wo/bac) by isolating SGMB from feces, mucosal surfaces of colorectum, and colorectal tissues and detecting SGMB DNA, via PCR and in situ hybridization (ISH) assays targeting SodA gene in colorectal tissues. Moreover, mRNA of IL1, IL-8, COX-2, IFN-γ, c-Myc, and Bcl-2 in colorectal tissues of studied groups was assessed via ISH and RT-PCR.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/genetics
  20. Looi ML, Dali AZ, Ali SA, Ngah WZ, Yusof YA
    Anal. Quant. Cytol. Histol., 2008 Apr;30(2):63-70.
    PMID: 18561741
    To assess the expression of p53, bcl-2 and Ki-67 in the progression of cervical neoplasia.
    Matched MeSH terms: Proto-Oncogene Proteins c-bcl-2/metabolism*
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