Displaying publications 21 - 40 of 89 in total

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  1. Caspase-dependent and -independent mechanisms in apoptosis induced by hydroquinone and catechol metabolites of remoxipride in HL-60 cells
    Inayat-Hussain SH, McGuinness SM, Johansson R, Lundstrom J, Ross D
    Chem Biol Interact, 2000 Aug 15;128(1):51-63.
    PMID: 10996300
    The hydroquinone and catechol like metabolites, NCQ344 and NCQ436 respectively, of the antipsychotic remoxipride have recently been demonstrated to induce apoptosis in myeloperoxidase (MPO)-rich human bone marrow progenitor and HL-60 cells [S.M. McGuinness, R. Johansson, J. Lundstrom, D. Ross, Induction of apoptosis by remoxipride metabolites in HL-60 and CD34+/CD19- human bone marrow progenitor cells: potential relevance to remoxipride-induced aplastic anemia, Chem. Biol. Interact. 121 (1999) 253-265]. In the present study, we determined the molecular mechanisms of apoptosis induced by these remoxipride metabolites in HL-60 cells. Our results show that apoptosis was accompanied by phosphatidylserine (PS) exposure, activation of caspases-9, -3, -7 and DNA cleavage. In HL-60 cells treated with the hydroquinone NCQ344 and catechol NCQ436, the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp. fluoromethyl ketone (Z-VAD.FMK) blocked DNA cleavage and activation of caspases-9, -3/-7. In addition, PS exposure was significantly but not completely inhibited by Z-VAD.FMK. These results demonstrate that although Z-VAD.FMK inhibitable caspases are necessary for maximal apoptosis induced by NCQ344 and NCQ436, additional caspase-independent processes may orchestrate changes leading to PS exposure during apoptosis induced by the remoxipride polyphenolic metabolites.
    Matched MeSH terms: Caspases/metabolism; Caspases/physiology*
  2. Thymoquinone prevents β-amyloid neurotoxicity in primary cultured cerebellar granule neurons
    Ismail N, Ismail M, Mazlan M, Latiff LA, Imam MU, Iqbal S, et al.
    Cell Mol Neurobiol, 2013 Nov;33(8):1159-69.
    PMID: 24101432 DOI: 10.1007/s10571-013-9982-z
    Thymoquinone (TQ), a bioactive constituent of Nigella sativa Linn (N. sativa) has demonstrated several neuropharmacological attributes. In the present study, the neuroprotective properties of TQ were investigated by studying its anti-apoptotic potential to diminish β-amyloid peptide 1-40 sequence (Aβ1-40)-induced neuronal cell death in primary cultured cerebellar granule neurons (CGNs). The effects of TQ against Aβ1-40-induced neurotoxicity, morphological damages, DNA condensation, the generation of reactive oxygen species, and caspase-3, -8, and -9 activation were investigated. Pretreatment of CGNs with TQ (0.1 and 1 μM) and subsequent exposure to 10 μM Aβ1-40 protected the CGNs against the neurotoxic effects of the latter. In addition, the CGNs were better preserved with intact cell bodies, extensive neurite networks, a loss of condensed chromatin and less free radical generation than those exposed to Aβ1-40 alone. TQ pretreatment inhibited Aβ1-40-induced apoptosis of CGNs via both extrinsic and intrinsic caspase pathways. Thus, the findings of this study suggest that TQ may prevent neurotoxicity and Aβ1-40-induced apoptosis. TQ is, therefore, worth studying further for its potential to reduce the risks of developing Alzheimer's disease.
    Matched MeSH terms: Caspases/metabolism
  3. Is vitamin E toxic to neuron cells?
    Then SM, Mazlan M, Mat Top G, Wan Ngah WZ
    Cell Mol Neurobiol, 2009 Jun;29(4):485-96.
    PMID: 19172392 DOI: 10.1007/s10571-008-9340-8
    Besides acting as potent free radical scavengers, tocopherols and tocotrienols have been known to have non-antioxidant properties such as the involvement of alpha-tocopherol (alphaT) in PKC pathway and the anti-cancer properties of gamma-tocotrienol (gammaT3). This study aims to elucidate whether protective effects shown by alphaT and gammaT3 in H(2)O(2)-induced neuron cultures have anti-apoptotic or pro-apoptotic tendency toward the initiation of neuronal apoptosis. H(2)O(2) is used to induce apoptosis in primary cerebellar neuron cultures which is attenuated by pretreatment of alphaT or gammaT3 at concentrations < or =10 microM. Similar to our previous work, gammaT3 was found to be neurotoxic at concentrations > or =100 microM, whereas alphaT showed no neurotoxicity. Cellular uptake of gammaT3 was higher than that of alphaT. Treating cells simultaneously with either gammaT3 or alphaT and with then H(2)O(2) led to higher expression of Bax and Bcl-2 than in neurons exposed to H(2)O(2) alone. Analysis of Bcl-2/Bax ratio as 'survival index' showed that both pretreatment of gammaT3 and alphaT followed by H(2)O(2) increase the 'survival index' of Bcl-2/Bax ratio compared to H(2)O(2)-treated cells, while treatment of gammaT3 alone decrease the ratio compared to unchanged Bcl2/Bax ratio of similar treatment with alphaT alone. Similar treatment of gammaT3 decreased p53 expression and activates p38 MAPK phosphorylation, whereas alphaT did not alter its expression compared to H(2)O(2)-treated cells. Treating neurons with only gammaT3 or alphaT increased the expression of Bax, Bcl-2, p53, and p38 MAPK compared to control with gammaT3 exerting stronger expression for proteins involved than alphaT. In conclusion, low doses of gammaT3 and alphaT confer neuroprotection to H(2)O(2)-treated neurons via their antioxidant mechanism but gammaT3 has stronger pro-apoptosis tendency than alphaT by activating molecules involved in the neuronal apoptotic pathway in the absence of H(2)O(2).
    Matched MeSH terms: Caspases/metabolism
  4. Growth arrest and non-apoptotic programmed cell death associated with the up-regulation of c-myc mRNA expression in T-47D breast tumor cells following exposure to Epipremnum pinnatum (L.) Engl. hexane extract
    Tan ML, Muhammad TS, Najimudin N, Sulaiman SF
    J Ethnopharmacol, 2005 Jan 15;96(3):375-83.
    PMID: 15619555
    Epipremnum pinnatum (L.) Engl. hexane extract produced a significant growth inhibition against T-47D breast carcinoma cells and analysis of cell death mechanisms indicated that the extract elicited a non-apoptotic programmed cell death. T-47D cells exposed to the extract at EC(50) concentration (72 h) for 24 h failed to demonstrate typical DNA fragmentation associated with apoptosis, as carried out using a modified TUNEL assay. In addition, acute exposure to the extract produced an insignificant regulation of caspase-3 and p53 mRNA expression but increased in the c-myc mRNA expression. Ultrastructural analysis using transmission electron microscope demonstrated distinct vacuolated cells, which strongly indicated a Type II non-apoptotic cell death although the changes in chromatin were also detected. The presence of non-apoptotic programmed cell death was then reconfirmed with annexin-V and propidium iodide staining. These findings suggested that up-regulation of c-myc mRNA expression may have contributed to the growth arrest and Type II non-apoptotic programmed cell death in the Epipremnum pinnatum (L.) Engl. hexane extract-treated T-47D cells.
    Matched MeSH terms: Caspases/metabolism
  5. Effects of tocotrienols on cell viability and apoptosis in normal murine liver cells (BNL CL.2) and liver cancer cells (BNL 1ME A.7R.1), in vitro
    Har CH, Keong CK
    Asia Pac J Clin Nutr, 2005;14(4):374-80.
    PMID: 16326644
    The effects of tocotrienols on murine liver cell viability and their apoptotic events were studied over a dose range of 0-32 microg mL(-1). Normal murine liver cells (BNL CL.2) and murine liver cancer cells (BNL 1ME A.7R.1) were treated with tocotrienols (T(3)), alpha tocopherol (alpha-T) and the chemo drug, Doxorubicin (Doxo, as a positive control). Cell viability assay showed that T(3) significantly (P < or = 0.05) lowered the percentage of BNL 1ME A.7R.1 cell viability in a dose-responsive manner (8-16 microg mL(-1)), whereas T did not show any significant (P>0.05) inhibition in cell viability with increasing treatment doses of 0-16 microg mL(-1). The IC(50) for tocotrienols were 9.8, 8.9, 8.1, 9.7, 8.1 and 9.3 microg mL(-1) at 12, 24, 36, 48, 60 and 72 hours respectively. Early apoptosis was detected 6 hours following T(3) treatment of BNL 1ME A.7R.1 liver cancer cells, using Annexin V-FITC fluorescence microscopy assay for apoptosis, but none were observed for the non-treated liver cancer cells at the average IC(50) of 8.98 microg mL(-1) tocotrienols for liver cancer cells. Several apoptotic bodies were detected in BNL 1ME A.7R.1 liver cancer cells at 6 hours post-treatment with tocotrienols (8.98 microg mL(-1)) using Acridine Orange/Propidium Iodide fluorescence assay. However, only a couple of apoptotic bodies were seen in the non-treated liver cancer cells and the BNL CL.2 normal liver cells. Some mitotic bodies were also observed in the T(3)-treated BNL 1ME A.7R.1 liver cancer cells but were not seen in the untreated BNL 1ME A.7R.1 cells and the BNL CL.2 liver cells. Following T(3)-treatment (8.98 microg mL(-1)) of the BNL 1ME A.7R.1 liver cancer cells, 24.62%, 25.53% and 44.90% of the cells showed elevated active caspase 3 activity at 9, 12 and 24 hours treatment period, respectively. DNA laddering studies indicated DNA fragmentation occurred in the T(3)-treated liver cancer cells, BNL 1ME A.7R.1 but not in non-treated liver cancer cells and the T(3)-treated and non-treated normal liver cells. These results suggest that tocotrienols were able to reduce the cell viability in the murine liver cancer cells at a dose of 8-32 microg mL(-1) and that this decrease in percentage cell viability may be due to apoptosis.
    Matched MeSH terms: Caspases/metabolism
  6. Fulltext Cycloart-24-ene-26-ol-3-one, a New Cycloartane Isolated from Leaves of Aglaia exima Triggers Tumour Necrosis Factor-Receptor 1-Mediated Caspase-Dependent Apoptosis in Colon Cancer Cell Line
    Leong KH, Looi CY, Loong XM, Cheah FK, Supratman U, Litaudon M, et al.
    PLoS One, 2016;11(4):e0152652.
    PMID: 27070314 DOI: 10.1371/journal.pone.0152652
    Plants in the Meliaceae family are known to possess interesting biological activities, such as antimalaral, antihypertensive and antitumour activities. Previously, our group reported the plant-derived compound cycloart-24-ene-26-ol-3-one isolated from the hexane extracts of Aglaia exima leaves, which shows cytotoxicity towards various cancer cell lines, in particular, colon cancer cell lines. In this report, we further demonstrate that cycloart-24-ene-26-ol-3-one, from here forth known as cycloartane, reduces the viability of the colon cancer cell lines HT-29 and CaCO-2 in a dose- and time-dependent manner. Further elucidation of the compound's mechanism showed that it binds to tumour necrosis factor-receptor 1 (TNF-R1) leading to the initiation of caspase-8 and, through the activation of Bid, in the activation of caspase-9. This activity causes a reduction in mitochondrial membrane potential (MMP) and the release of cytochrome-C. The activation of caspase-8 and -9 both act to commit the cancer cells to apoptosis through downstream caspase-3/7 activation, PARP cleavage and the lack of NFkB translocation into the nucleus. A molecular docking study showed that the cycloartane binds to the receptor through a hydrophobic interaction with cysteine-96 and hydrogen bonds with lysine-75 and -132. The results show that further development of the cycloartane as an anti-cancer drug is worthwhile.
    Matched MeSH terms: Caspases/metabolism
  7. Fulltext Geranylated 4-Phenylcoumarins Exhibit Anticancer Effects against Human Prostate Cancer Cells through Caspase-Independent Mechanism
    Suparji NS, Chan G, Sapili H, Arshad NM, In LL, Awang K, et al.
    PLoS One, 2016;11(3):e0151472.
    PMID: 26974436 DOI: 10.1371/journal.pone.0151472
    Geranylated 4-phenylcoumarins, DMDP-1 & -2 isolated from Mesua elegans were investigated for anticancer potential against human prostate cancer cells. Treatment with DMDP-1 & -2 resulted in cell death in a time and dose dependent manner in an MTT assay on all cancer cell lines tested with the exception of lung adenocarcinoma cells. DMDP-1 showed highest cytotoxic efficacy in PC-3 cells while DMDP-2 was most potent in DU 145 cells. Flow cytometry indicated that both coumarins were successful to induce programmed cell death after 24 h treatment. Elucidation on the mode-of-action via protein arrays and western blotting demonstrated death induced without any significant expressions of caspases, Bcl-2 family proteins and cleaved PARP, thus suggesting the involvement of caspase-independent pathways. In identifying autophagy, analysis of GFP-LC3 showed increased punctate in PC-3 cells pre-treated with CQ and treated with DMDP-1. In these cells decreased expression of autophagosome protein, p62 and cathepsin B further confirmed autophagy. In contrary, the DU 145 cells pre-treated with CQ and treated with DMDP-2 has reduced GFP-LC3 punctate although the number of cells with obvious GFP-LC3 puncta was significantly increased in the inhibitor-treated cells. The increase level of p62 suggested leakage of cathepsin B into the cytosol to trigger potential downstream death mediators. This correlated with increased expression of cathepsin B and reduced expression after treatment with its inhibitor, CA074. Also auto-degradation of calpain-2 upon treatment with DMDP-1 &-2 and its inhibitor alone, calpeptin compared with the combination treatment, further confirmed involvement of calpain-2 in PC-3 and DU 145 cells. Treatment with DMDP-1 & -2 also showed up-regulation of total and phosphorylated p53 levels in a time dependent manner. Hence, DMDP-1 & -2 showed ability to activate multiple death pathways involving autophagy, lysosomal and endoplasmic reticulum death proteins which could potentially be manipulated to develop anti-cancer therapy in apoptosis resistant cells.
    Matched MeSH terms: Caspases/metabolism
  8. Fulltext Induction of apoptosis and oxidative stress in estrogen receptor-negative breast cancer, MDA-MB231 cells, by ethanolic mango seed extract
    Abdullah AS, Mohammed AS, Rasedee A, Mirghani ME, Al-Qubaisi MS
    BMC Complement Altern Med, 2015;15:45.
    PMID: 25881293 DOI: 10.1186/s12906-015-0575-x
    In this study, the effect of mango kernel extract in the induction of apoptosis of the breast cancer (MDA-MB-231) cell line was examined. This is an attempt to discover alternatives to current therapeutic regimes in the treatment of breast cancers.
    Matched MeSH terms: Caspases/metabolism
  9. Caspases-3 and -7 are activated in goniothalamin-induced apoptosis in human Jurkat T-cells
    Inayat-Hussain SH, Osman AB, Din LB, Ali AM, Snowden RT, MacFarlane M, et al.
    FEBS Lett., 1999 Aug 13;456(3):379-83.
    PMID: 10462048
    Goniothalamin, a plant styrylpyrone derivative isolated from Goniothalamus andersonii, induced apoptosis in Jurkat T-cells as assessed by the externalisation of phosphatidylserine. Immunoblotting showed processing of caspases-3 and -7 with the appearance of their catalytically active large subunits of 17 and 19 kDa, respectively. Activation of these caspases was further evidenced by detection of poly(ADP-ribose) polymerase cleavage (PARP). Pre-treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) blocked apoptosis and the resultant cleavage of these caspases and PARP. Our results demonstrate that activation of at least two effector caspases is a key feature of goniothalamin-induced apoptosis in Jurkat T-cells.
    Matched MeSH terms: Caspases/metabolism*
  10. Fulltext Induction of Apoptosis and Cytotoxicity by Isothiocyanate Sulforaphene in Human Hepatocarcinoma HepG2 Cells
    Kntayya SB, Ibrahim MD, Mohd Ain N, Iori R, Ioannides C, Abdull Razis AF
    Nutrients, 2018 Jun 04;10(6).
    PMID: 29866995 DOI: 10.3390/nu10060718
    Glucoraphenin, a glucosinolate present in large quantities in radish is hydrolysed by myrosinase to form the isothiocyanate sulforaphene, which is believed to be responsible for its chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aim of the study is to assess the cytotoxicity of sulforaphene in HepG2 cells and evaluate its potential to enhance apoptosis. The cytotoxicity of sulforaphene in HepG2 cells was carried out ensuing an initial screening with two other cell lines, MFC-7 and HT-29, where sulforaphene displayed highest toxicity in HepG2 cells following incubation at 24, 48 and 72 h. In contrast, the intact glucosinolate showed no cytotoxicity. Morphological studies indicated that sulforaphene stimulated apoptosis as exemplified by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. The Annexin V assay revealed significant increases in apoptosis and the same treatment increased the activity of caspases -3/7 and -9, whereas a decline in caspase-8 was observed. Impairment of cell proliferation was indicated by cell cycle arrest at the Sub G₀/G₁ phase as compared to the other phases. It may be concluded that sulforaphene, but not its parent glucosinolate, glucoraphenin, causes cytotoxicity and stimulates apoptosis in HepG2 cells.
    Matched MeSH terms: Caspases/metabolism
  11. Nimbolide induces apoptosis in human nasopharyngeal cancer cells
    Chien SY, Hsu CH, Lin CC, Chuang YC, Lo YS, Hsi YT, et al.
    Environ Toxicol, 2017 Aug;32(8):2085-2092.
    PMID: 28383207 DOI: 10.1002/tox.22423
    Nasopharyngeal carcinoma (NPC), a tumor arising from epithelial cells that cover the surface and line the nasopharynx, is a rare malignancy worldwide but is prevalent in certain geographical areas, such as Southern Asia (Taiwan, Hong Kong, Singapore, Malaysia, and Southern China) and North Africa. Despite advances in diagnostic techniques and improvements in treatment modalities, the prognosis of NPC remains poor. Therefore, an effective chemotherapy regimen that enhances tumor sensitivity to chemotherapeutics is urgently required. Nimbolide, derived from Azadirachta indica, has a wide range of beneficial effects, including anti-inflammatory and anticancer properties. The present study evaluated the antitumor activity of nimbolide in NPC cells and its underlying mechanisms. Our results revealed that the treatment of HONE-1 cells with nimbolide potently inhibited cell viability. Moreover, nimbolide led to cell cycle arrest, which subsequently activated caspase-3, -8, and -9 and poly (ADP-ribose) polymerase to induce cell apoptosis. Moreover, nimbolide induced Bik, Bax, and t-Bid expression in HONE-1 cells. The results indicated that nimbolide induces apoptosis through the modulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways. Nimbolide induces apoptosis in human NPC cells and is a potential chemopreventive agent against NPC proliferation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2085-2092, 2017.
    Matched MeSH terms: Caspases/metabolism
  12. Fulltext Clausenidin induces caspase-dependent apoptosis in colon cancer
    Waziri PM, Abdullah R, Yeap SK, Omar AR, Kassim NK, Malami I, et al.
    BMC Complement Altern Med, 2016 Jul 29;16:256.
    PMID: 27473055 DOI: 10.1186/s12906-016-1247-1
    BACKGROUND: Clausena excavata Burm.f. is a shrub traditionally used to treat cancer patients in Asia. The main bioactive chemical components of the plant are alkaloids and coumarins. In this study, we isolated clausenidin from the roots of C. excavata to determine its apoptotic effect on the colon cancer (HT-29) cell line.
    METHOD: We examined the effect of clausenidin on cell viability, ROS generation, DNA fragmentation, mitochondrial membrane potential in HT-29 cells. Ultrastructural analysis was conducted for morphological evidence of apoptosis in the treated HT-29 cells. In addition, we also evaluated the effect of clausenidin treatment on the expression of caspase 3 and 9 genes and proteins in HT-29 cells.
    RESULT: Clausenidin induced a G0/G1 cell cycle arrest in HT-29 cells with significant (p 
    Matched MeSH terms: Caspases/metabolism*
  13. Rabdosia rubescens Linn: green synthesis of gold nanoparticles and their anticancer effects against human lung cancer cells A549
    Zhang X, Tan Z, Jia K, Zhang W, Dang M
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):2171-2178.
    PMID: 31159596 DOI: 10.1080/21691401.2019.1620249
    Nanomedicine is a rapidly emerging field and is reported to be a promising tool for treating various diseases. Green synthesized nanoparticles are documented to possess a potent anticancer effect. Rabdosia rubescens is a Chinese plant which is also one of the components of PC-SPES and used to treat prostate cancer. In the present study, we synthesized the gold nanoparticles from R. rubescens (RR-AuNP) and analyzed its anticancer activity against the lung carcinoma A549 cell lines. Since lung cancer is reported to be with increased morbidity and decreased survival rate. The biosynthesized RR-AuNP were confirmed using UV-Visible spectrophotometer, size and shape of RR-AuNP were assessed by DLS, TEM and EDX. The biomolecules present in RR-AuNP and its topographical structure were detected using FTIR, SAED and AFM analysis. MTT assay was performed to detect the IC50 dose of RR-AuNP and its apoptotic effect was assessed by detecting the caspases activation, ROS generation. The anticancer effect of RR-AuNP was confirmed by DAPI staining, TUNEL assay and its molecular mechanism were confirmed by assessing the apoptotic signalling molecules protein expression. Our results illustrate that RR-AuNP showed a strong absorption peak at 550 nm and the RRAuNP were polydispersed nanospheres with size of 130 nm. RR-AuNP IC50 dose against A549 lung carcinoma cell line was detected to be at 25 µg/ml. The results of DAPI staining, TUNEL and immunoblotting analysis confirms both the 25 µg/ml and 50 µg/ml of RR-AuNP possess potent anticancer and apoptotic effect, suggesting that RR-AuNP that it may be a persuasive molecule to treat lung cancer.
    Matched MeSH terms: Caspases/metabolism
  14. Fulltext Silver nanoparticles biosynthesized using Achillea biebersteinii flower extract: apoptosis induction in MCF-7 cells via caspase activation and regulation of Bax and Bcl-2 gene expression
    Baharara J, Namvar F, Ramezani T, Mousavi M, Mohamad R
    Molecules, 2015 Feb 05;20(2):2693-706.
    PMID: 25665064 DOI: 10.3390/molecules20022693
    Silver nanoparticles (Ag-NPs), the most popular nanoparticles, possess unique properties. Achillea biebersteinii is a plant of the Asteraceae family rich in active antitumor components. The aim of this research was the characterization and investigation of the cytotoxic properties of Ag-NPs synthesized using A. biebersteinii flower extract, on a human breast cancer cell line. The Ag-NPs were synthesized after approximately 180 min of reaction at 40 °C, then they were characterized by UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The anti-apoptosis effect of Ag-NPs on the MCF-7 cell line was investigated by MTT assay, DAPI and acridine orange staining and caspase activity. The transcriptional expression of bax, bcl-2, caspase-3, -8 and -9 were also evaluated by RT-PCR. The TEM images revealed that the Ag-NPs morphology had a different shape. The DLS indicated that the average hydrodynamic diameter of the biosynthesized Ag-NPs was around 12 nm. By UV-visible spectroscopy the strongest absorbance peak was observed at 460 nm. The FTIR results also showed interaction between the plant extract and Ag-NPs due to the similarity in the peak patterns. The EDS results showed that Ag-NPs display an absorption peak at 3 keV, indicating the presence of the element silver. The Ag-NPs caused a dose-dependent decrease in cell viability, fragmentation in nucleic acid, inhibited the proliferation and induction of apoptosis on MCF-7 by suppressing specific cell cycle genes, and simulation programmed cell dead genes. Further investigation is required to establish the potential of this novel and promising approach in cancer therapy.
    Matched MeSH terms: Caspases/metabolism*
  15. Fulltext Vitex Rotundifolia Fractions Induced Apoptosis in Human Breast Cancer T-47D Cell Line via Activation of Extrinsic and Intrinsic Pathway
    Chaudhry GE, Jan R, Naveed Zafar M, Mohammad H, Muhammad TST
    Asian Pac J Cancer Prev, 2019 Dec 01;20(12):3555-3562.
    PMID: 31870094 DOI: 10.31557/APJCP.2019.20.12.3555
    OBJECTIVE: Breast cancer is the most frequently diagnosed cancer worldwide. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the extract and fractions of Vitex rotundifolia (leaves) in breast cancer cell line, T-47D.

    METHODS: The cytotoxicity activity was measured using MTS assay. The mode of cell death was analysed by early (phosphatidylserine externalization) and late apoptosis (DNA fragmentation). The caspases 8, 9, 3/7 and apoptotic proteins bax, bcl-2 study were done by western blot and ELISA method.

    RESULTS: The methanol extract was found to inhibit 50% growth of T-47D cells at the concentration of 79.43µg/ml respectively after 72hr. From seven fractions, fraction F1, F2 and F3 produced cytotoxicity effects in T-47D cell line with IC50 (72hr) < 30µg/ml. The results obtained by Annexin V/PI apoptosis detection assay and TUNEL assay suggest that active fractions of  Vitex rotundifolia induced early and late apoptosis (DNA fragmentation) in T-47D cell line. Moreover, western blot analysis and Caspase GloTM luminescent assay demonstrated that fractions F2 and F3 triggered apoptotic cell death via activation of caspases -8, -9 and -3/7 and up-regulation of  Bax and down-regulation of Bcl-2 protein.  Furthermore, chemical profiling confirms the presence of potential metabolites (vitexicarpin) in fractions of Vitex rotundifolia.

    CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in fractions of Vitex rotundifolia as future cancer therapeutic agent for the treatment of breast cancer.
    .

    Matched MeSH terms: Caspases/metabolism
  16. Fulltext Evaluation of phytoestrogens in inducing cell death mediated by decreasing Annexin A1 in Annexin A1-knockdown leukemia cells
    Hasan M, Kumolosasi E, Jasamai M, Jamal JA, Azmi N, Rajab NF
    Daru, 2020 Jun;28(1):97-108.
    PMID: 31912375 DOI: 10.1007/s40199-019-00320-0
    BACKGROUND: Phytoestrogens are plant compounds that are structurally similar to estrogen and that possess anti-cancer properties. Previous studies have reported that coumestrol, daidzein and genistein could induce cell death by reducing Annexin A1 protein in leukemic cell lines. Annexin A1 (ANXA1) is involved in cell progression, metastasis, and apoptosis in several types of cancer cells. The present study sought to investigate if the effects of phytoestrogens on apoptosis, cell cycle arrest and phagocytosis in ANXA1-knockdown leukemic cells are mediated through ANXA1 or occurred independently.

    METHODS: Transfection of ANXA1 siRNA was conducted to downregulate ANXA1 expression in Jurkat, K562 and U937 cells. Apoptosis and cell cycle assays were conducted using flow cytometry. Western blot was performed to evaluate ANXA1, caspases and Bcl-2 proteins expression. Phagocytosis was determined using hematoxylin and eosin staining.

    RESULTS: The expression of ANXA1 after the knockdown was significantly downregulated in all cell lines. Genistein significantly induced apoptosis associated with an upregulation of procaspase-3, -9, and - 1 in Jurkat cells. The Bcl-2 expression showed no significant difference in Jurkat, K562 and U937 cells. Treatment with phytoestrogens increased procaspase-1 expression in Jurkat and U937 cells while no changes were detected in K562 cells. Flow cytometry analysis demonstrated that after ANXA1 knockdown, coumestrol and genistein caused cell cycle arrest at G2/M phase in selected type of cells. The percentage of phagocytosis and phagocytosis index increased after the treatment with phytoestrogens in all cell lines.

    CONCLUSION: Phytoestrogens induced cell death in ANXA1-knockdown leukemia cells, mediated by Annexin A1 proteins. Graphical abstract.

    Matched MeSH terms: Caspases/metabolism
  17. Fulltext Cytotoxic and apoptotic effects of heat killed Mycobacterium indicus pranii (MIP) on various human cancer cell lines
    Subramaniam M, In LL, Kumar A, Ahmed N, Nagoor NH
    Sci Rep, 2016;6:19833.
    PMID: 26817684 DOI: 10.1038/srep19833
    Mycobacterium indicus pranii (MIP) is a non-pathogenic mycobacterium, which has been tested on several cancer types like lung and bladder where tumour regression and complete recovery was observed. In discovering the potential cytotoxic elements, a preliminary test was carried out using four different fractions consisting of live bacteria, culture supernatant, heat killed bacteria and heat killed culture supernatant of MIP against two human cancer cells A549 and CaSki by 3-(4,5-dimethyl thiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis was investigated in MCF-7 and ORL-115 cancer cells by poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation assays. Among four MIP fractions, only heat killed MIP fraction (HKB) showed significant cytotoxicity in various cancer cells with inhibitory concentration, IC50 in the range 5.6-35.0 μl/(1.0 × 10(6) MIP cells/ml), while cytotoxicity effects were not observed in the remaining fractions. HKB did not show cytotoxic effects on non-cancerous cells contrary to cancerous cells, suggesting its safe usage and ability to differentially recognize between these cells. Evaluation on PARP assay further suggested that cytotoxicity in cancer cells were potentially induced via caspase-mediated apoptosis. The cytotoxic and apoptotic effects of MIP HKB have indicated that this fraction can be a good candidate to further identify effective anti-cancer agents.
    Matched MeSH terms: Caspases
  18. Fulltext Induction of cytotoxicity by Bruguiera gymnorrhiza in human breast carcinoma (MCF-7) cell line via activation of the intrinsic pathway
    Chaudhry GE, Rahman NH, Sevakumaran V, Ahmad A, Mohamad H, Zafar MN, et al.
    J Adv Pharm Technol Res, 2020 10 10;11(4):233-237.
    PMID: 33425710 DOI: 10.4103/japtr.JAPTR_81_20
    Breast cancer is among the frequently occurring cancer worldwide. The foremost underline aim of this study was to determine the growth inhibitory effect along with mechanistic study of a Bruguiera gymnorrhiza extract on MCF-7. The cytotoxicity activity was determined by using the MTS assay. Butanol extract exhibited the maximum cytotoxicity activity against the MCF-7 cells with IC50 of 3.39 μg/mL, followed by diethyl ether and methanol extract (IC50 at 16.22 μg/mL and 37.15 μg/mL, respectively) at 72 h. The DeadEndTM Colorimetric Apoptosis Detection System confirmed the induction of apoptosis (via DNA fragmentation) in MCF-7 cells. Both butanol and diethyl ether extracts of B. gymnorrhiza significantly increase the caspase-3 level. However, the diethyl ether extract induced higher caspase-9 levels compared to caspase-8, suggesting that the intrinsic pathway was the major route in the process of apoptosis. Thin-layer chromatography profiling demonstrated the presence of phenolic, terpene, and alkaloid compounds in crude methanol, diethyl ether, and butanol extracts. The phytochemicals present in the extracts of B. gymnorrhiza might have the potential to be a future therapeutic agent against breast cancer.
    Matched MeSH terms: Caspases
  19. Malaysian tualang honey and its potential anti-cancer properties: a review
    Ahmad Firdaus Khalid, Yoke KY, Jun JT
    Sains Malaysiana, 2018;47:2705-2711.
    The use of honey as a therapeutic agent dates back at 8000 years and has markedly increased interest into its potential
    health benefits. The by-products of the flower nectar have a complex chemical composition which promotes benefits in
    underlying mechanism of human diseases. Malaysian Tualang Honey (MTH) is a multifloral jungle honey produced by
    the rock bee (Apis dorsata). This review consolidates the results of carious studies involving biochemical assays of tissue
    culture and animal trials of anti-cancer properties of MTH. Often studied in the context of breast cancer cell lines, MTH
    has promising data for possible mechanisms in anti-cancer activity. These include apoptosis via depolarization of the
    mitochondrial membrane, caspase-dependent apoptosis, reduction of angiogenesis and the promotion of cell cycle arrest
    without posing cytotoxic effect on normal cell lines. Despite positive outcomes in tissue cultures, the oral administration
    of MTH in breast cancer animal models showed slower tumour progression, reduction in tumour size and better grading
    of histological features. The alleviation of breast carcinogenesis via modulation of hematologic, estrogenic and apoptotic
    activities promotes MTH as a promising anticancer agent. With confidence in a conclusion that MTH is a useful treatment
    for cancer, further experimental and clinical studies should be conducted.
    Matched MeSH terms: Caspases
  20. Fulltext Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage
    Bakshi HA, Zoubi MSA, Hakkim FL, Aljabali AAA, Rabi FA, Hafiz AA, et al.
    Nutrients, 2020 06 26;12(6).
    PMID: 32604971 DOI: 10.3390/nu12061901
    Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
    Matched MeSH terms: Caspases
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