Displaying publications 81 - 100 of 106 in total

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  1. Fulltext Gallic acid induced apoptotic events in HCT-15 colon cancer cells
    Subramanian AP, Jaganathan SK, Mandal M, Supriyanto E, Muhamad II
    World J Gastroenterol, 2016 Apr 21;22(15):3952-61.
    PMID: 27099438 DOI: 10.3748/wjg.v22.i15.3952
    AIM: To investigate the inhibitory action of diet-derived phenolic compound gallic acid (GA) against HCT-15 colon cancer cells.
    METHODS: The antiproliferative effect of GA against colon cancer cells was determined by performing thiazolyl blue tetrazolium bromide (MTT) assay. The colony forming ability of GA treated colon cancer cells was evaluated using the colony forming assay. The cell cycle changes induced by GA in HCT-15 cells were analyzed by propidium iodide staining. Levels of reactive oxygen species (ROS) and mitochondrial membrane potential of HCT-15 exposed to GA was assessed using 2',7'-dichlorfluorescein-diacetate and rhodamine-123 respectively, with the help of flow cytometry. Morphological changes caused by GA treatment in the colon cancer cells were identified by scanning electron microscope and photomicrograph examination. Apoptosis was confirmed using flow cytometric analysis of GA treated HCT-15 cells after staining with Yo-Pro-1.
    RESULTS: MTT assay results illustrated that GA has an inhibitory effect on HCT-15 cells with IC50 value of 740 μmol/L. A time-dependent inhibition of colony formation was evident with GA treatment. Cell cycle arrest was evident from the accumulation of GA treated HCT-15 cells at sub-G1 phase (0.98 ± 1.03 vs 58.01 ± 2.05) with increasing exposure time. Flow cytometric analysis of GA treated HCT-15 cells depicted early events associated with apoptosis like lipid layer breakage and fall in mitochondrial membrane potential apart from an increase in the generation of ROS which were in a time dependent manner. SEM and photomicrograph images of the GA-treated cells displayed membrane blebbing and cell shrinking characteristics of apoptosis. Further apoptosis confirmation by Yo-Pro-1 staining also showed the time-dependent increase of apoptotic cells after treatment.
    CONCLUSION: These results show that GA induced ROS dependent apoptosis and inhibited the growth of colon cancer cells.
    KEYWORDS: Apoptosis; Cell cycle; Colon cancer; Gallic acid; Lipid layer break; Reactive oxygen species
    Matched MeSH terms: Membrane Potential, Mitochondrial
  2. Fulltext (6E,10E) Isopolycerasoidol and (6E,10E) Isopolycerasoidol Methyl Ester, Prenylated Benzopyran Derivatives from Pseuduvaria monticola Induce Mitochondrial-Mediated Apoptosis in Human Breast Adenocarcinoma Cells
    Taha H, Looi CY, Arya A, Wong WF, Yap LF, Hasanpourghadi M, et al.
    PLoS One, 2015;10(5):e0126126.
    PMID: 25946039 DOI: 10.1371/journal.pone.0126126
    Phytochemicals from Pseuduvaria species have been reported to display a wide range of biological activities. In the present study, a known benzopyran derivative, (6E,10E) isopolycerasoidol (1), and a new benzopyran derivative, (6E,10E) isopolycerasoidol methyl ester (2), were isolated from a methanol extract of Pseuduvaria monticola leaves. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and LCMS-QTOF, and by comparison with previously published data. The anti-proliferative and cytotoxic effects of these compounds on human breast cancer cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient in reducing cell viability of breast cancer cells. Flow cytometry analysis demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated by an increase in phosphotidylserine exposure. Both compounds elevated ROS production, leading to reduced mitochondrial membrane potential and increased plasma membrane permeability in breast cancer cells. These effects occurred concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down-regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in the nucleus. Taken together, our data demonstrate that (1) and (2) induce intrinsic mitochondrial-mediated apoptosis in human breast cancer cells, which provides the first pharmacological evidence for their future development as anticancer agents.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  3. Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line
    Taha MM, Sheikh BY, Salim LZ, Mohan S, Khan A, Kamalidehghan B, et al.
    Cell Mol Biol (Noisy-le-grand), 2016 May 30;62(6):97-101.
    PMID: 27262811
    Nigella sativa is also known for its properties as a traditional herbal healing for many ailments. In this study, the anticancer properties of thyomquinone (TQ), the active ingredient of N. sativa, were studied using ovarian cancer cell line (Caov-3 cells). The anti-proliferative activity of TQ was determined using MTT and the apoptosis was investigated using Flowcytometry and Annexin-V Assays. Multiparameteric cytotoxicity bioassays were used to quantify the changes in cell permeability and mitochondrial membrane potential. Reactive oxygen species (ROS) and apoptosis-involved cell markers were examined to verify cell death mechanism. The MTT-assay showed that TQ induces anti-proliferative activity on Caov-3 with an IC50 of 6.0±0.03 μg/mL, without any cytotoxic activity towards WRL-68 normal hepatocytes. A significant induction of early phase of apoptosis was shown by annexin-V analysis. Treatment of Caov-3 cells with TQ induces decreases in plasma membrane permeability and mitochondrial membrane potential. Visible decrease in the nuclear area was also observed. A significant decrease is observed in Bcl-2 while Bax is down-regulated. TQ-triggered ROS-mediated has found to be associated with Hsp70 dysregulation, an indicator of oxidative injury. We found that TQ induced anti-cancer effect involves intrinsic pathway of apoptosis and cellular oxidative stress. Our results considered collectively indicated that thyomquinone may be a potential agent for ovarian cancer drug development.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  4. ROS-Mediated Mitochondrial Pathway is Required for Manilkara Zapota (L.) P. Royen Leaf Methanol Extract Inducing Apoptosis in the Modulation of Caspase Activation and EGFR/NF-κB Activities of HeLa Human Cervical Cancer Cells
    Tan BL, Norhaizan ME, Chan LC
    Evid Based Complement Alternat Med, 2018;2018:6578648.
    PMID: 29977314 DOI: 10.1155/2018/6578648
    Manilkara zapota (L.) P. Royen (family: Sapotaceae) is commonly called sapodilla, or locally known as ciku. The detailed mechanisms underlying Manilkara zapota leaf methanol extract against HeLa human cervical cancer cells have yet to be investigated. Therefore, our present study is designed to investigate the ability to induce apoptosis and the underlying mechanisms of Manilkara zapota leaf methanol extract inducing cytotoxicity in HeLa cells. The apoptotic cell death was assessed using Annexin V-propidium iodide staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential activities were measured using dichlorodihydrofluorescein diacetate and MitoLite Orange, respectively, by NovoCyte Flow Cytometer. Bax and Bcl-2 expression were evaluated using Enzyme-Linked Immunosorbent Assay. Caspase-3 activity was determined using a colorimetric assay. The associated biological interaction pathways were evaluated using quantitative real-time PCR. Our data showed that HeLa cells were relatively more sensitive to Manilkara zapota leaf methanol extract than other cancer cell lines studied. Overall analyses revealed that Manilkara zapota leaf methanol extract can inhibit the viability of HeLa cells, induce mitochondrial ROS generation, and inhibit nuclear factor-kappa B (NF-κB) and epidermal growth factor receptor (EGFR) transcriptional activities. Our results suggested that Manilkara zapota leaf methanol extract might represent a potential anticervical cancer agent.
    Matched MeSH terms: Membrane Potential, Mitochondrial
  5. Fulltext Neuroprotective Effects of Biochanin A against β-Amyloid-Induced Neurotoxicity in PC12 Cells via a Mitochondrial-Dependent Apoptosis Pathway
    Tan JW, Kim MK
    Molecules, 2016 Apr 25;21(5).
    PMID: 27120593 DOI: 10.3390/molecules21050548
    Alzheimer's disease is considered one of the major neurodegenerative diseases and is characterized by the production of β-amyloid (Aβ) proteins and progressive loss of neurons. Biochanin A, a phytoestrogen compound found mainly in Trifolium pratense, was used in the present study as a potential alternative to estrogen replacement therapy via the investigation of its neuroprotective effects against Aβ25-35-induced toxicity, as well as of its potential mechanisms of action in PC12 cells. Exposure of these cells to the Aβ25-35 protein significantly increased cell viability loss and apoptosis. However, the effects induced by Aβ25-35 were markedly reversed in the present of biochanin A. Pretreatment with biochanin A attenuated the cytotoxic effect of the Aβ25-35 protein by decreasing viability loss, LDH release, and caspase activity in cells. Moreover, we found that expression of cytochrome c and Puma were reduced, alongside with the restoration of Bcl-2/Bax and Bcl-xL/Bax ratio in the presence of biochanin A, which led to a decrease in the apoptotic rate. These data demonstrate that mitochondria are involved in the protective effect of biochanin A against Aβ25-35 and that this drug attenuated Aβ25-35-induced PC12 cell injury and apoptosis by preventing mitochondrial dysfunction. Thus, biochanin A might raise a possibility as a potential therapeutic agent for Alzheimer's disease and other related neurodegenerative diseases.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  6. Fulltext Bile acids at neutral and acidic pH induce apoptosis and gene cleavages in nasopharyngeal epithelial cells: implications in chromosome rearrangement
    Tan SN, Sim SP
    BMC Cancer, 2018 04 12;18(1):409.
    PMID: 29649994 DOI: 10.1186/s12885-018-4327-4
    BACKGROUND: Chronic rhinosinusitis (CRS) increases the risk of developing nasopharyngeal carcinoma (NPC) while nasopharyngeal reflux is known to be one of the major aetiological factors of CRS. Bile acid (BA), the component of gastric duodenal contents, has been recognised as a carcinogen. BA-induced apoptosis was suggested to be involved in human malignancies. Cells have the potential and tendency to survive apoptosis. However, cells that evade apoptosis upon erroneous DNA repair may carry chromosome rearrangements. Apoptotic nuclease, caspase-activated deoxyribonuclease (CAD) has been implicated in mediating translocation in leukaemia. We hypothesised that BA-induced apoptosis may cause chromosome breaks mediated by CAD leading to chromosome rearrangement in NPC. This study targeted the AF9 gene located at 9p22 because 9p22 is one of the most common deletion sites in NPC.

    METHODS: We tested the ability of BA at neutral and acidic pH in inducing phosphatidylserine (PS) externalisation, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) disruption, and caspase 3/7 activity in normal nasopharyngeal epithelial (NP69) and NPC (TWO4) cells. Inverse-PCR (IPCR) was employed to detect AF9 gene cleavages. To investigate the role of CAD in mediating these cleavages, caspase inhibition was performed. IPCR bands representing AF9 cleaved fragments were sequenced.

    RESULTS: BA-treated cells showed higher levels of PS externalisation, ROS production, MMP loss and caspase 3/7 activity than untreated control cells. The effect of BA in the induction of these intracellular events was enhanced by acid. BA at neutral and acidic pH also induced significant cleavage of the AF9 gene. These BA-induced gene cleavages were inhibited by Z-DEVD-FMK, a caspase-3 inhibitor. Intriguingly, a few chromosome breaks were identified within the AF9 region that was previously reported to participate in reciprocal translocation between the mixed lineage leukaemia (MLL) and AF9 genes in an acute lymphoblastic leukaemia (ALL) patient.

    CONCLUSIONS: These findings suggest a role for BA-induced apoptosis in mediating chromosome rearrangements in NPC. In addition, CAD may be a key player in chromosome cleavages mediated by BA-induced apoptosis. Persistent exposure of sinonasal tract to gastric duodenal refluxate may increase genomic instability in surviving cells.

    Matched MeSH terms: Membrane Potential, Mitochondrial
  7. Phyla nodiflora L. Extracts Induce Apoptosis and Cell Cycle Arrest in Human Breast Cancer Cell Line, MCF-7
    Teoh PL, Liau M, Cheong BE
    Nutr Cancer, 2019;71(4):668-675.
    PMID: 30663402 DOI: 10.1080/01635581.2018.1559942
    Phyla nodiflora L. has been used as medicinal remedies for various ailments due to its antioxidant, anti-inflammatory, anti-bacterial, anti-tumor activity. Previously, we found that the plant extracts induced DNA fragmentation in MCF-7. This study was to investigate the modes of action of P. nodiflora in inhibiting breast cancer cells using leaf ethyl acetate (EA leaf), stem ethyl acetate (EA stem) and stem methanol (Met stem) extracts. The MTT assay showed that the anti-proliferative effects of P. nodiflora extracts were selective towards MCF-7 with a minimal effect on MCF10A. Morphological changes such as cell shrinkage and nuclear condensation were observed in treated cells. We found that induction of apoptosis by EA leaf and EA stem was mitochondrial-dependent while loss of mitochondrial membrane potential was not found in Met stem-treated cells. In addition, the expression levels of AIFM1, CASP9, CFLAR, and IGF1R were altered after treatment. Decreased BCL-2 expression was found in treated cells while BAX and caspases' expression was upregulated or maintained. All extracts caused perturbation of cell cycle at S phase by dysregulating the expression of cell cycle regulators such as CDKs and cyclins. Our findings indicate that P. nodiflora inhibits MCF-7 cells by inducing apoptosis and perturbing cell cycle.
    Matched MeSH terms: Membrane Potential, Mitochondrial
  8. Chemical composition and cytotoxic properties of Clinacanthus nutans root extracts
    Teoh PL, Cheng AY, Liau M, Lem FF, Kaling GP, Chua FN, et al.
    Pharm Biol, 2017 Dec;55(1):394-401.
    PMID: 27931178
    CONTEXT: Clinacanthus nutans Lindau (Acanthaceae) is a medicinal plant that has been reported to have anti-inflammatory, antiviral, antimicrobial and antivenom activities. In Malaysia, it has been widely claimed to be effective in various cancer treatments but scientific evidence is lacking.

    OBJECTIVE: This study investigates the chemical constituents, anti-proliferative, and apoptotic properties of C. nutans root extracts.

    MATERIALS AND METHODS: The roots were subjected to solvent extraction using methanol and ethyl acetate. The anti-proliferative effects of root extracts were tested at the concentrations of 10 to 50 μg/mL on MCF-7 and HeLa by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay for 72 h. Morphological changes were observed under light microscope. Pro-apoptotic effects of root extracts were examined using flow cytometric analysis and RT-PCR. The chemical compositions of root extracts were detected using GC-MS.

    RESULTS: The proliferation of MCF-7 cells was inhibited with the IC50 values of 35 and 30 μg/mL, respectively, for methanol and ethyl acetate root extracts. The average inhibition of HeLa cells was ∼25%. Induction of apoptosis in MCF-7 was supported by chromatin condensation, down-regulation of BCL2 and unaltered expression of BAX. However, only ethyl acetate extract caused the loss of mitochondrial membrane potential. GC-MS analysis revealed the roots extracts were rich with terpenoids and phytosterols.

    DISCUSSION AND CONCLUSIONS: The results demonstrated that root extracts promote apoptosis by suppressing BCL2 via mitochondria-dependent or independent manner. The identified compounds might work solely or cooperatively in regulating apoptosis. However, further studies are required to address this.

    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  9. Acacia catechu seed extract provokes cytotoxicity via apoptosis by intrinsic pathway in HepG2 cells
    Thangavelu L, Geetha RV, Devaraj E, Dua K, Chellappan DK, Balusamy SR
    Environ Toxicol, 2022 Mar;37(3):446-456.
    PMID: 34800081 DOI: 10.1002/tox.23411
    Acacia catechu Willd (Fabaceae) is a thorny tree widely distributed in India and commonly used as traditional Ayurvedic medicine for various ailments. The current study evaluates the cytotoxic potentials of A. catechu ethanolic seed extract (ACSE) in HepG2 cells, a human hepatocellular carcinoma cell line. The HepG2 cells were treated with 0.1, 0.3, 1, 3, 10, 30, 100, 300 and 1000 μg/ml of ACSE and the cytotoxic effect was evaluated by MTT and lactate dehydrogenase (LDH) leakage assays. The IC50 of ACSE was found at 77.04 μg/ml and therefore, further studies were carried out with the concentrations of 35 and 70 μg/ml. The intracellular reactive oxygen species (ROS) generation and apoptosis-related morphological changes were evaluated. Gene expressions of Bax, Bcl-2, cytochrome C (Cyt-c), caspases-9 and 3 were analyzed by qPCR. The ACSE treatments caused LDH leakage was associated with an increased ROS generation. The increased ROS generation was associated with the downregulation of intracellular antioxidant enzyme superoxide dismutase and reduced glutathione content. AO/EB and PI staining also confirmed chromatin condensation and apoptosis. The flow cytometric analysis showed an accumulation of HepG2 cells at sub G0/G1 (apoptotic) phase upon ACSE treatments. The ACSE induced cytotoxicity and oxidative stress were related to increased apoptotic marker gene expressions such as Bax, Cyt-c, caspase-9 and 3, and decreased anti-apoptotic marker Bcl-2. The current finding suggests that ACSE has apoptosis-inducing potential via the mitochondrial pathway in HepG2 cells.
    Matched MeSH terms: Membrane Potential, Mitochondrial
  10. Fulltext Induction of Apoptosis in MCF-7 Cells via Oxidative Stress Generation, Mitochondria-Dependent and Caspase-Independent Pathway by Ethyl Acetate Extract of Dillenia suffruticosa and Its Chemical Profile
    Tor YS, Yazan LS, Foo JB, Wibowo A, Ismail N, Cheah YK, et al.
    PLoS One, 2015;10(6):e0127441.
    PMID: 26047480 DOI: 10.1371/journal.pone.0127441
    Dillenia suffruticosa, which is locally known as Simpoh air, has been traditionally used to treat cancerous growth. The ethyl acetate extract of D. suffruticosa (EADs) has been shown to induce apoptosis in MCF-7 breast cancer cells in our previous study. The present study aimed to elucidate the molecular mechanisms involved in EADs-induced apoptosis and to identify the major compounds in the extract. EADs was found to promote oxidative stress in MCF-7 cells that led to cell death because the pre-treatment with antioxidants α-tocopherol and ascorbic acid significantly reduced the cytotoxicity of the extract (P<0.05). DCFH-DA assay revealed that treatment with EADs attenuated the generation of intracellular ROS. Apoptosis induced by EADs was not inhibited by the use of caspase-inhibitor Z-VAD-FMK, suggesting that the cell death is caspase-independent. The use of JC-1 dye reflected that EADs caused disruption in the mitochondrial membrane potential. The related molecular pathways involved in EADs-induced apoptosis were determined by GeXP multiplex system and Western blot analysis. EADs is postulated to induce cell cycle arrest that is p53- and p21-dependent based on the upregulated expression of p53 and p21 (P<0.05). The expression of Bax was upregulated with downregulation of Bcl-2 following treatment with EADs. The elevated Bax/Bcl-2 ratio and the depolarization of mitochondrial membrane potential suggest that EADs-induced apoptosis is mitochondria-dependent. The expression of oxidative stress-related AKT, p-AKT, ERK, and p-ERK was downregulated with upregulation of JNK and p-JNK. The data indicate that induction of oxidative-stress related apoptosis by EADs was mediated by inhibition of AKT and ERK, and activation of JNK. The isolation of compounds in EADs was carried out using column chromatography and elucidated using the nuclear resonance magnetic analysis producing a total of six compounds including 3-epimaslinic acid, kaempferol, kaempferide, protocatechuic acid, gallic acid and β-sitosterol-3-O-β-D-glucopyranoside. The cytotoxicity of the isolated compounds was determined using MTT assay. Gallic acid was found to be most cytotoxic against MCF-7 cell line compared to others, with IC50 of 36 ± 1.7 μg/mL (P<0.05). In summary, EADs generated oxidative stress, induced cell cycle arrest and apoptosis in MCF-7 cells by regulating numerous genes and proteins that are involved in the apoptotic signal transduction pathway. Therefore, EADs has the potential to be developed as an anti-cancer agent against breast cancer.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  11. Attenuation of oxidative stress induced mitochondrial dysfunction and cytotoxicity in fibroblast cells by sulfated polysaccharide from Padina gymnospora
    Vasantharaja R, Stanley Abraham L, Gopinath V, Hariharan D, Smita KM
    Int J Biol Macromol, 2019 Mar 01;124:50-59.
    PMID: 30445094 DOI: 10.1016/j.ijbiomac.2018.11.104
    In this present study, isolation, characterization and protective effect of sulfated polysaccharide (SP) isolated from the brown algae Padina gymnospora was investigated. SP was isolated and characterized through FT-IR, 1H NMR, TGA, GC-MS and CHN analysis. The molecular weight of SP was found to be 16 kDa. The isolated SP contains 29.4 ± 0.35% of sulfate, 27 ± 0.11% of fucose, 0.05 ± 0.12% of protein, respectively. Furthermore, SP exhibits its excellent radical scavenging effects were evaluated by DPPH, ABTS radical scavenging and reducing power assays. Moreover, pretreatment with SP significantly mitigates H2O2 induced cytotoxicity in L-929 cells in a dose dependent manner. Furthermore, SP pretreatment ameliorates oxidative stress induced apoptosis and DNA damage, alleviates the generation of intracellular reactive oxygen species (ROS) and restores mitochondrial membrane potential (MMP) in L-929 cells through its antioxidant potential. Together, these results suggest that SP can be exploited as a natural antioxidant in the food and pharmaceutical industries.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  12. Polyalthia longifolia Methanolic Leaf Extracts (PLME) induce apoptosis, cell cycle arrest and mitochondrial potential depolarization by possibly modulating the redox status in hela cells
    Vijayarathna S, Oon CE, Chen Y, Kanwar JR, Sasidharan S
    Biomed Pharmacother, 2017 May;89:499-514.
    PMID: 28249252 DOI: 10.1016/j.biopha.2017.02.075
    Medicinal plants have been accepted as a gold mine, with respect to the diversity of their phytochemicals. Many medicinal plants extracts are potential anticancer agents. Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is one of the most significant native medicinal plants and is found throughout Malaysia. Hence, the present study was intended to assess the anticancer properties of P. longifolia leaf methanolic extract (PLME) and its underlying mechanisms. The Annexin V/PI flow cytometry analysis showed that PLME induces apoptosis in HeLa cells in dose-dependent manner whereas the PI flow cytometric analysis for cell cycle demonstrated the accumulation of cells at sub G0/G1, G0/G1 and G2/M phases. Investigation with JC-1 flow cytometry analysis indicated increase in mitochondria membrane potential depolarisation corresponding to increase in PLME concentrations. PLME was also shown to influence intracellular reactive oxygen species (ROS) by exerting anti-oxidant (half IC50) and pro-oxidant (IC50and double IC50) affect against HeLa cells. PLME treatment also displayed DNA damage in HeLa cells in concentration depended fashion. The proteomic profiling array exposed the expression of pro-apoptotic and anti-apoptotic proteins upon PLME treatment at IC50concentration in HeLa cells. Pro-apoptotic proteins; BAX, BAD, cytochrome c, caspase-3, p21, p27 and p53 were found to be significantly up-regulated while anti-apoptotic proteins; BCL-2 and BCL-w were found to be significantly down-regulated. This investigation postulated the role of p53 into mediating apoptosis, cell cycle arrest and mitochondrial potential depolarisation by modulating the redox status of HeLa cells.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects*
  13. Clausenidin from Clausena excavata induces apoptosis in hepG2 cells via the mitochondrial pathway
    Waziri PM, Abdullah R, Yeap SK, Omar AR, Abdul AB, Kassim NK, et al.
    J Ethnopharmacol, 2016 Dec 24;194:549-558.
    PMID: 27729282 DOI: 10.1016/j.jep.2016.10.030
    ETHNOPHARMACOLOGICAL RELEVANCE: Clausena excavata Burm.f. is used locally in folk medicine for the treatment of cancer in South East Asia.

    AIM OF THE STUDY: To determine the mechanism of action of pure clausenidin crystals in the induction of hepatocellular carcinoma (hepG2) cells apoptosis.

    MATERIALS AND METHODS: Pure clausenidin was isolated from Clausena excavata Burm.f. and characterized using (1)H and (13)C NMR spectra. Clausenidin-induced cytotoxicity was determined by MTT assay. The morphology of hepG2 after treatment with clausenidin was determined by fluorescence and Scanning Electron Microscopy. The effect of clausenidin on the apoptotic genes and proteins were determined by real-time qPCR and protein array profiling, respectively. The involvement of the mitochondria in clausenidin-induced apoptosis was investigated using MMP, caspase 3 and 9 assays.

    RESULTS: Clausenidin induced significant (p<0.05) and dose-dependent apoptosis of hepG2 cells. Cell cycle assay showed that clausenidin induced a G2/M phase arrest, caused mitochondrial membrane depolarization and significantly (p<0.05) increased expression of caspases 3 and 9, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, clausenidin caused decreased expression of the anti-apoptotic protein, Bcl 2 and increased expression of the pro-apoptotic protein, Bax. This finding was confirmed by the downregulation of Bcl-2 gene and upregulation of the Bax gene in the treated hepG2 cells.

    CONCLUSION: Clausenidin extracted from Clausena excavata Burm.f. is an anti-hepG2 cell compound as shown by its ability to induce apoptosis through the mitochondrial pathway of apoptosis. Clausenidin can potentially be developed into an anticancer compound.

    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  14. Bioassay-guided isolation of neuroprotective compounds from Loranthus parasiticus against H₂O₂-induced oxidative damage in NG108-15 cells
    Wong DZ, Kadir HA, Ling SK
    J Ethnopharmacol, 2012 Jan 6;139(1):256-64.
    PMID: 22107836 DOI: 10.1016/j.jep.2011.11.010
    A parasite plant, Loranthus parasiticus (Loranthaceae), which is generally known as benalu teh (in Malay), Sang Ji Sheng (in Chinese), and baso-kisei (in Japan) distributed in south and southwest part of China, has been used as a folk medicine for the treatment of schizophrenia in southwest China. Loranthus parasiticus has various uses in folk and traditional medicines for bone, brain, kidney, liver, expels wind-damp, and prevents miscarriage.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  15. Fulltext Induction of Mitochondria-Mediated Apoptosis in Ca Ski Human Cervical Cancer Cells Triggered by Mollic Acid Arabinoside Isolated from Leea indica
    Wong YH, Abdul Kadir H
    Evid Based Complement Alternat Med, 2012;2012:684740.
    PMID: 22203877 DOI: 10.1155/2012/684740
    Leea indica is a medicinal plant traditionally used to treat cancer. Through bioassay-guided approach, we isolated mollic acid arabinoside (MAA), for the first time from Leea indica. Here, we present the apoptosis-inducing effect of MAA on Ca Ski cervical cancer cells. Based on DAPI staining, MAA-treated cells manifested nuclear shrinkage, condensation, and fragmentation. We further confirmed the fragmentation of DNA using TUNEL assay. During early apoptosis, MAA caused the perturbation of plasma membrane through externalization of PS, followed by the formation of apoptotic blebs. Prior to these events, MAA triggered rapid dissipation of the mitochondrial membrane potential. In the upstream, MAA increased the expression of Bax, decreased the expression of Bcl-2, and augmented the Bax/Bcl-2 ratio. These findings suggested that MAA induced mitochondrial-mediated apoptosis in Ca Ski cells and thus provide the scientific explanation for the traditional application of this herbal medicine in cancer treatment.
    Matched MeSH terms: Membrane Potential, Mitochondrial
  16. Fulltext Synergistic anticancer effects of a bioactive subfraction of Strobilanthes crispus and tamoxifen on MCF-7 and MDA-MB-231 human breast cancer cell lines
    Yaacob NS, Kamal NN, Norazmi MN
    BMC Complement Altern Med, 2014;14:252.
    PMID: 25034326 DOI: 10.1186/1472-6882-14-252
    Development of tumour resistance to chemotherapeutic drugs and concerns over their toxic effects has led to the increased use of medicinal herbs or natural products by cancer patients. Strobilanthes crispus is a traditional remedy for many ailments including cancer. Its purported anticancer effects have led to the commercialization of the plant leaves as medicinal herbal tea, although the scientific basis for its use has not been established. We previously reported that a bioactive subfraction of Strobilanthes crispus leaves (SCS) exhibit potent cytotoxic activity against human breast cancer cell lines. The current study investigates the effect of this subfraction on cell death activities induced by the antiestrogen drug, tamoxifen, in estrogen receptor-responsive and nonresponsive breast cancer cells.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  17. Influence of 17β-estradiol on 15-deoxy-δ12,14 prostaglandin J2 -induced apoptosis in MCF-7 and MDA-MB-231 cells
    Yaacob NS, Nasir R, Norazmi MN
    Asian Pac J Cancer Prev, 2013;14(11):6761-7.
    PMID: 24377602
    The nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ), is expressed in various cancer cells including breast, prostate, colorectal and cervical examples. An endogenous ligand of PPARγ, 15-deoxy-Δ12,14 prostaglandin J2 (PGJ2), is emerging as a potent anticancer agent but the exact mechanism has not been fully elucidated, especially in breast cancer. The present study compared the anticancer effects of PGJ2 on estrogen receptor alpha (ERα)-positive (MCF-7) and ERα-negative (MDA-MB-231) human breast cancer cells. Based on the reported signalling cross-talk between PPARγ and ERα, the effect of the ERα ligand, 17β-estradiol (E2) on the anticancer activities of PGJ2 in both types of cells was also explored. Here we report that PGJ2 inhibited proliferation of both MCF-7 and MDA-MB-231 cells by inducing apoptotic cell death with active involvement of mitochondria. The presence of E2 potentiated PGJ2-induced apoptosis in MCF-7, but not in MDA-MB-231 cells. The PPARγ antagonist, GW9662, failed to block PGJ2-induced activities but potentiated its effects in MCF-7 cells, instead. Interestingly, GW9662 also proved capable of inducing apoptotic cell death. It can be concluded that E2 enhances PPARγ-independent anticancer effects of PGJ2 in the presence of its receptor.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects*
  18. Fulltext Leea indica Ethyl Acetate Fraction Induces Growth-Inhibitory Effect in Various Cancer Cell Lines and Apoptosis in Ca Ski Human Cervical Epidermoid Carcinoma Cells
    Yau Hsiung W, Abdul Kadir H
    Evid Based Complement Alternat Med, 2011;2011:293060.
    PMID: 21423690 DOI: 10.1155/2011/293060
    The anticancer potential of Leea indica, a Chinese medicinal plant was investigated for the first time. The crude ethanol extract and fractions (ethyl acetate, hexane, and water) of Leea indica were evaluated their cytotoxicity on various cell lines (Ca Ski, MCF 7, MDA-MB-435, KB, HEP G2, WRL 68, and Vero) by MTT assay. Leea indica ethyl acetate fraction (LIEAF) was found showing the greatest cytotoxic effect against Ca Ski cervical cancer cells. Typical apoptotic morphological changes such as DNA fragmentation and chromatin condensation were observed in LIEAF-treated cells. Early signs of apoptosis such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential indicated apoptosis induction. This was further substantiated by dose- and time-dependent accumulation of sub-G(1) cells, depletion of intracellular glutathione, and activation of caspase-3. In conclusion, these results suggested that LIEAF inhibited cervical cancer cells growth by inducing apoptosis and could be developed as potential anticancer drugs.
    Matched MeSH terms: Membrane Potential, Mitochondrial
  19. The aminopeptidase inhibitor, z-L-CMK, is toxic and induces cell death in Jurkat T cells through oxidative stress
    Yeo EH, Goh WL, Chow SC
    Toxicol. Mech. Methods, 2018 Mar;28(3):157-166.
    PMID: 28849708 DOI: 10.1080/15376516.2017.1373882
    The leucine aminopeptidase inhibitor, benzyloxycarbonyl-leucine-chloromethylketone (z-L-CMK), was found to be toxic and readily induce cell death in Jurkat T cells. Dose-response studies show that lower concentration of z-L-CMK induced apoptosis in Jurkat T cells whereas higher concentration causes necrosis. In z-L-CMK-induced apoptosis, both the initiator caspases (-8 and -9) and effector caspases (-3 and -6) were processed to their respective subunits. However, the caspases remained intact in z-L-CMK-induced necrosis. The caspase inhibitor, z-VAD-FMK inhibited z-L-CMK-mediated apoptosis and caspase processing but has no effect on z-L-CMK-induced necrosis in Jurkat T cells. The high mobility group protein B1 (HMGB1) protein was found to be released into the culture medium by the necrotic cells and not the apoptotic cells. These results indicate that the necrotic cell death mediated by z-L-CMK at high concentrations is via classical necrosis rather than secondary necrosis. We also demonstrated that cell death mediated by z-L-CMK was associated with oxidative stress via the depletion of intracellular glutathione (GSH) and increase in reactive oxygen species (ROS), which was blocked by N-acetyl cysteine. Taken together, the results demonstrated that z-L-CMK is toxic to Jurkat T cells and induces apoptosis at low concentrations, while at higher concentrations the cells die of necrosis. The toxic side effects in Jurkat T cells mediated by z-L-CMK are associated with oxidative stress via the depletion of GSH and accumulation of ROS.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  20. Fulltext Edible bird's nest ameliorates oxidative stress-induced apoptosis in SH-SY5Y human neuroblastoma cells
    Yew MY, Koh RY, Chye SM, Othman I, Ng KY
    BMC Complement Altern Med, 2014;14:391.
    PMID: 25308934 DOI: 10.1186/1472-6882-14-391
    Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the senile population with manifestation of motor disability and cognitive impairment. Reactive oxygen species (ROS) is implicated in the progression of oxidative stress-related apoptosis and cell death of the midbrain dopaminergic neurons. Its interplay with mitochondrial functionality constitutes an important aspect of neuronal survival in the perspective of PD. Edible bird's nest (EBN) is an animal-derived natural food product made of saliva secreted by swiftlets from the Aerodamus genus. It contains bioactive compounds which might confer neuroprotective effects to the neurons. Hence this study aims to investigate the neuroprotective effect of EBN extracts in the neurotoxin-induced in vitro PD model.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
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