Displaying publications 1 - 20 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 Events associated with apoptotic effect of p-Coumaric acid in HCT-15 colon cancer cells
    Jaganathan SK, Supriyanto E, Mandal M
    World J Gastroenterol, 2013 Nov 21;19(43):7726-34.
    PMID: 24282361 DOI: 10.3748/wjg.v19.i43.7726
    AIM: To investigate the events associated with the apoptotic effect of p-Coumaric acid, one of the phenolic components of honey, in human colorectal carcinoma (HCT-15) cells.

    METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium-bromide assay was performed to determine the antiproliferative effect of p-Coumaric acid against colon cancer cells. Colony forming assay was conducted to quantify the colony inhibition in HCT 15 and HT 29 colon cancer cells after p-Coumaric acid treatment. Propidium Iodide staining of the HCT 15 cells using flow cytometry was done to study the changes in the cell cycle of treated cells. Identification of apoptosis was done using scanning electron microscope and photomicrograph evaluation of HCT 15 cells after exposing to p-Coumaric acid. Levels of reactive oxygen species (ROS) of HCT 15 cells exposed to p-Coumaric acid was evaluated using 2', 7'-dichlorfluorescein-diacetate. Mitochondrial membrane potential of HCT-15 was assessed using rhodamine-123 with the help of flow cytometry. Lipid layer breaks associated with p-Coumaric acid treatment was quantified using the dye merocyanine 540. Apoptosis was confirmed and quantified using flow cytometric analysis of HCT 15 cells subjected to p-Coumaric acid treatment after staining with YO-PRO-1.

    RESULTS: Antiproliferative test showed p-Coumaric acid has an inhibitory effect on HCT 15 and HT 29 cells with an IC₅₀ (concentration for 50% inhibition) value of 1400 and 1600 μmol/L respectively. Colony forming assay revealed the time-dependent inhibition of HCT 15 and HT 29 cells subjected to p-Coumaric acid treatment. Propidium iodide staining of treated HCT 15 cells showed increasing accumulation of apoptotic cells (37.45 ± 1.98 vs 1.07 ± 1.01) at sub-G1 phase of the cell cycle after p-Coumaric acid treatment. HCT-15 cells observed with photomicrograph and scanning electron microscope showed the signs of apoptosis like blebbing and shrinkage after p-Coumaric acid exposure. Evaluation of the lipid layer showed increasing lipid layer breaks was associated with the growth inhibition of p-Coumaric acid. A fall in mitochondrial membrane potential and increasing ROS generation was observed in the p-Coumaric acid treated cells. Further apoptosis evaluated by YO-PRO-1 staining also showed the time-dependent increase of apoptotic cells after treatment.

    CONCLUSION: These results depicted that p-Coumaric acid inhibited the growth of colon cancer cells by inducing apoptosis through ROS-mitochondrial pathway.

    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  3. 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
  4. Suppressing growth, migration, and invasion of human hepatocellular carcinoma HepG2 cells by Catharanthus roseus‑silver nanoparticles
    Azhar NA, Ghozali SZ, Abu Bakar SA, Lim V, Ahmad NH
    Toxicol In Vitro, 2020 Sep;67:104910.
    PMID: 32526345 DOI: 10.1016/j.tiv.2020.104910
    Application of silver nanoparticles serves as a new approach in cancer treatment due to its unique features. Biosynthesis of silver nanoparticles using plant is advantageous since they are easily accessible, nontoxic and produce quicker reaction compared to other methods. To evaluate the cytotoxicity, mechanism of cell death and DNA damage of biosynthesized Catharanthus roseus-silver nanoparticles on human liver cancer (HepG2) cells. The antiproliferative activity of Catharanthus roseus‑silver nanoparticles was measured using MTT assay. The cytotoxic effects were further evaluated by measuring nitric oxide and reactive oxygen species (ROS). The mechanism of cell death was determined by annexin-FITC/propidium iodide, mitochondrial membrane potential (MMP) and cell cycle assays. The assessment of DNA damage was evaluated using Comet assay method. The uptake of the nanoparticles were evaluated by Transmission Electron Microscopy (TEM). Catharanthus roseus‑silver nanoparticles has inhibited the proliferation of HepG2 cells in a time-dependent manner with a median IC50 value of 3.871 ± 0.18 μg/mL. The concentration of nitrite and ROS were significantly higher than control. The cell death was due to apoptosis associated with MMP loss, cell cycle arrest, and extensive DNA damage. TEM analysis indicated the presence of free nanoparticles and endosomes containing the nanoparticles. The findings show that Catharanthus roseus‑silver nanoparticles have produced cytotoxic effects on HepG2 cells and thus may have a potential to be used as an anticancer treatment, particularly for hepatocellular carcinoma.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  5. Fulltext Goniothalamin induces coronary artery smooth muscle cells apoptosis: the p53-dependent caspase-2 activation pathway
    Chan KM, Rajab NF, Siegel D, Din LB, Ross D, Inayat-Hussain SH
    Toxicol. Sci., 2010 Aug;116(2):533-48.
    PMID: 20498002 DOI: 10.1093/toxsci/kfq151
    Goniothalamin (GN), a styryl-lactone isolated from Goniothalamus andersonii, has been demonstrated to possess antirestenostic properties by inducing apoptosis on coronary artery smooth muscle cells (CASMCs). In this study, the molecular mechanisms of GN-induced CASMCs apoptosis were further elucidated. Apoptosis assessment based on the externalization of phosphatidylserine demonstrated that GN induces CASMCs apoptosis in a concentration-dependent manner. The GN-induced DNA damage occurred with concomitant elevation of p53 as early as 2 h, demonstrating an upstream signal for apoptosis. However, the p53 elevation in GN-treated CASMCs was independent of NAD(P)H: quinone oxidoreductase 1 and Mdm-2 expression. An increase in hydrogen peroxide and reduction in free thiols confirmed the role for oxidative stress in GN treatment. Pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-FMK) that significantly abrogated GN-induced CASMCs apoptosis suggested the involvement of caspase(s). The role of apical caspase-2, -8, and -9 was then investigated, and sequential activation of caspase-2 and -9 but not caspase-8 leading to downstream caspase-3 cleavage was observed in GN-treated CASMCs. Reduction of ATP level and decrease in oxygen consumption further confirmed the role of mitochondria in GN-induced apoptosis in CASMCs. The mitochondrial release of cytochrome c was seen without mitochondrial membrane potential loss and was independent of cardiolipin. These data provide insight into the mechanisms of GN-induced apoptosis, which may have important implications in the development of drug-eluting stents.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  6. Fulltext A Schiff base-derived copper (II) complex is a potent inducer of apoptosis in colon cancer cells by activating the intrinsic pathway
    Hajrezaie M, Paydar M, Moghadamtousi SZ, Hassandarvish P, Gwaram NS, Zahedifard M, et al.
    ScientificWorldJournal, 2014;2014:540463.
    PMID: 24737979 DOI: 10.1155/2014/540463
    Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87  μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25  μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  7. 3,5-dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells
    Roslie H, Chan KM, Rajab NF, Velu SS, Kadir SA, Bunyamin I, et al.
    J Toxicol Sci, 2012 Feb;37(1):13-21.
    PMID: 22293408
    A series of 22 stilbene derivatives based on resveratrol were synthesized incorporating acetoxy-, benzyloxy-, carboxy-, chloro-, hydroxy- and methoxy functional groups. We examined the cytotoxicity of these 22 stilbenes in human K562 chronic myelogenous leukemia cells. Only four compounds were cytotoxic namely 4'-hydroxy-3-methoxystilbene (15), 3'-acetoxy-4-chlorostilbene (19), 4'-hydroxy-3,5-dimethoxystilbene or pterostilbene (3) and 3,5-dibenzyloxy-4'-hydroxystilbene (28) with IC(50)s of 78 µM, 38 µM, 67 µM and 19.5 µM respectively. Further apoptosis assessment on the most potent compound, 28, confirmed that the cells underwent apoptosis based on phosphatidylserine externalization and loss of mitochondrial membrane potential. Importantly, we observed a concentration-dependent activation of caspase-9 as early as 2 hr with resultant caspase-3 cleavage in 28-induced apoptosis. Additionally, a structure-activity relationship (SAR) study proposed a possible mechanism of action for compound 28. Taken together, our data suggests that the pro-apoptotic effects of 28 involve the intrinsic mitochondrial pathway characterized by an early activation of caspase-9.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  8. Increased aqueous solubility and proapoptotic activity of potassium koetjapate against human colorectal cancer cells
    Jafari SF, Khadeer Ahamed MB, Iqbal MA, Al Suede FS, Khalid SH, Haque RA, et al.
    J Pharm Pharmacol, 2014 Oct;66(10):1394-409.
    PMID: 25039905 DOI: 10.1111/jphp.12272
    Recently, we have isolated koetjapic acid (KA) from Sandoricum koetjape and identified its selective anticancer potentiality against colorectal carcinoma. KA is quite likely to be useful as a systemic anticancer agent against colorectal malignancy. However, with extremely low solubility, KA has to be converted into a biocompatible solubilized form without compromising the bioefficacy. Objective of this study is to enhance solubility of KA and to evaluate anticancer efficacy of potassium koetjapate in human colorectal cancer cells.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  9. Fulltext Hypoxia-preconditioned mesenchymal stem cells attenuate bleomycin-induced pulmonary fibrosis
    Lan YW, Choo KB, Chen CM, Hung TH, Chen YB, Hsieh CH, et al.
    Stem Cell Res Ther, 2015;6:97.
    PMID: 25986930 DOI: 10.1186/s13287-015-0081-6
    Idiopathic pulmonary fibrosis is a progressive diffuse parenchymal lung disorder of unknown etiology. Mesenchymal stem cell (MSC)-based therapy is a novel approach with great therapeutic potential for the treatment of lung diseases. Despite demonstration of MSC grafting, the populations of engrafted MSCs have been shown to decrease dramatically 24 hours post-transplantation due to exposure to harsh microenvironments. Hypoxia is known to induce expression of cytoprotective genes and also secretion of anti-inflammatory, anti-apoptotic and anti-fibrotic factors. Hypoxic preconditioning is thought to enhance the therapeutic potency and duration of survival of engrafted MSCs. In this work, we aimed to prolong the duration of survival of engrafted MSCs and to enhance the effectiveness of idiopathic pulmonary fibrosis transplantation therapy by the use of hypoxia-preconditioned MSCs.
    Matched MeSH terms: Membrane Potential, Mitochondrial
  10. Fulltext Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties
    Samie N, Muniandy S, Kanthimathi MS, Haerian BS, Azudin RE
    Sci Rep, 2016 Apr 13;6:24172.
    PMID: 27072064 DOI: 10.1038/srep24172
    The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml respectively, after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-ƙB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines.
    Matched MeSH terms: Membrane Potential, Mitochondrial
  11. Fulltext Synthesis, characterization and apoptotic activity of quinazolinone Schiff base derivatives toward MCF-7 cells via intrinsic and extrinsic apoptosis pathways
    Zahedifard M, Faraj FL, Paydar M, Yeng Looi C, Hajrezaei M, Hasanpourghadi M, et al.
    Sci Rep, 2015 Jun 25;5:11544.
    PMID: 26108872 DOI: 10.1038/srep11544
    The current study investigated the cytotoxic effect of 3-(5-chloro-2-hydroxybenzylideneamino)-2-(5-chloro-2-hydroxyphenyl)-2,3-dihydroquinazolin-41(H)-one (A) and 3-(5-nitro-2-hydroxybenzylideneamino)-2-(5-nitro-2-hydroxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (B) on MCF-7, MDA-MB-231, MCF-10A and WRL-68 cells. The mechanism involved in apoptosis was assessed to evaluate the possible pathways induced by compound A and B. MTT assay results using A and B showed significant inhibition of MCF-7 cell viability, with IC50 values of 3. 27 ± 0.171 and 4.36 ± 0.219 μg/mL, respectively, after a 72 hour treatment period. Compound A and B did not demonstrate significant cytotoxic effects towards MDA-MB-231, WRL-68 and MCF-10A cells. Acute toxicity tests also revealed an absence of toxic effects on mice. Fluorescent microscopic studies confirmed distinct morphological changes (membrane blebbing and chromosome condensation) corresponding to typical apoptotic features in treated MCF-7 cells. Using Cellomics High Content Screening (HCS), we found that compound A and B could trigger the release of cytochrome c from mitochondria to the cytosol. The release of cytochrome c activated the expression of caspases-9 and then stimulated downstream executioner caspase-3/7. In addition, caspase-8 showed remarkable activity, followed by inhibition of NF-κB activation in A-and B-treated MCF-7 cells. The results indicated that A and B could induce apoptosis via a mechanism that involves either extrinsic or intrinsic pathways.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  12. Fulltext Geranylated 4-phenylcoumarins extracted from Mesua elegans induced caspase-independent cell death in prostate cancer cell lines through calpain-2 and cathepsin B
    Sapili H, Ho CS, Malagobadan S, Arshad NM, Nagoor NH
    Sci Rep, 2020 01 22;10(1):986.
    PMID: 31969640 DOI: 10.1038/s41598-020-57781-6
    Geranylated 4-phenylcoumarins DMDP-1 and DMDP-2 isolated from Mesua elegans were elucidated for their role in inducing caspase-independent programmed cell death (CI-PCD) in prostate cancer cell lines, PC-3 and DU 145, respectively. Cell homeostasis disruption was demonstrated upon treatment, as shown by the increase in calcium ion through colourimetric assay and endoplasmic reticulum (ER) stress markers GRP 78 and p-eIF2α through western blot. Subsequently, cytoplasmic death protease calpain-2 also showed increased activity during DMDP-1 & -2 treatments, while lysosomic death protease cathepsin B activity was significantly increased in PC-3 treated with DMDP-1. Flow cytometry showed a reduction in mitochondrial membrane potential in both cell lines, while western blotting showed translocation of mitochondrial death protease AIF into the cytoplasm in its truncated form. Furthermore, DMDP-1 & -2 treatments caused significant increase in superoxide level and oxidative DNA damage. Concurrent inhibition of calpain-2 and cathepsin B during the treatment showed an attenuation of cell death in both cell lines. Hence, DMDP-1 & -2 induce CI-PCD in prostate cancer cell lines through calpain-2 and cathepsin B.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  13. Fulltext Chalcomoracin is a potent anticancer agent acting through triggering Oxidative stress via a mitophagy- and paraptosis-dependent mechanism
    Han H, Chou CC, Li R, Liu J, Zhang L, Zhu W, et al.
    Sci Rep, 2018 06 22;8(1):9566.
    PMID: 29934599 DOI: 10.1038/s41598-018-27724-3
    Chalocomoracin (CMR), one of the major secondary metabolites found in fungus-infected mulberry leaves, is a potent anticancer agent. However, its anticancer mechanism remains elusive. Here, we demonstrated the potent anti-tumor activity and molecular mechanism of CMR both in vitro and in vivo. We showed for the first time that CMR treatment markedly promoted paraptosis along with extensive cytoplasmic vacuolation derived from the endoplasmic reticulum, rather than apoptosis, in PC-3 and MDA-MB-231cell lines. Additional studies revealed that ectopic expression of Myc-PINK1 (PTEN-induced kinase 1), a key regulator of mitophagy, rendered LNCap cells susceptible to CMR-induced paraptosis, suggesting that the mitophagy-dependent pathway plays a crucial role in inducing paraptosis by activating PINK1. CMR treatment directly upregulated PINK1 and downregulated Alix genes in MDA-MB-231 and PC-3 cell lines. Furthermore, mitophagy signaling and paraptosis with cytoplasmic vacuolation could be blocked by antioxidant N-acetylcysteine (NAC), indicating the novel pathway was triggered by reactive oxygen species (ROS) production. An in vivo MDA-MB-231 xenograft tumor model revealed that CMR suppressed tumor growth by inducing vacuolation production through the same signal changes as those observed in vitro. These data suggest that CMR is a potential therapeutic entity for cancer treatment through a non-apoptotic pathway.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  14. Fulltext Exceedingly Higher co-loading of Curcumin and Paclitaxel onto Polymer-functionalized Reduced Graphene Oxide for Highly Potent Synergistic Anticancer Treatment
    Muthoosamy K, Abubakar IB, Bai RG, Loh HS, Manickam S
    Sci Rep, 2016 Sep 06;6:32808.
    PMID: 27597657 DOI: 10.1038/srep32808
    Metastasis of lung carcinoma to breast and vice versa accounts for one of the vast majority of cancer deaths. Synergistic treatments are proven to be the effective method to inhibit malignant cell proliferation. It is highly advantageous to use the minimum amount of a potent toxic drug, such as paclitaxel (Ptx) in ng/ml together with a natural and safe anticancer drug, curcumin (Cur) to reduce the systemic toxicity. However, both Cur and Ptx suffer from poor bioavailability. Herein, a drug delivery cargo was engineered by functionalizing reduced graphene oxide (G) with an amphiphilic polymer, PF-127 (P) by hydrophobic assembly. The drugs were loaded via pi-pi interactions, resulting in a nano-sized GP-Cur-Ptx of 140 nm. A remarkably high Cur loading of 678 wt.% was achieved, the highest thus far compared to any other Cur nanoformulations. Based on cell proliferation assay, GP-Cur-Ptx is a synergistic treatment (CI 
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  15. Fulltext Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells
    Nassir AM, Shahzad N, Ibrahim IAA, Ahmad I, Md S, Ain MR
    Saudi Pharm J, 2018 Sep;26(6):876-885.
    PMID: 30202231 DOI: 10.1016/j.jsps.2018.03.009
    Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC50 and IC90) of 15.6 ± 1.49 and 41.1 ± 2.19 μM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200 μM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.
    Matched MeSH terms: Membrane Potential, Mitochondrial
  16. Fulltext Malaysian macroalga Padina australis Hauck attenuates high dose corticosterone-mediated oxidative damage in PC12 cells mimicking the effects of depression
    Subermaniam K, Yow YY, Lim SH, Koh OH, Wong KH
    Saudi J Biol Sci, 2020 Jun;27(6):1435-1445.
    PMID: 32489279 DOI: 10.1016/j.sjbs.2020.04.042
    Oxidative damage has been associated with the pathophysiology of depression. Macroalgae are equipped with antioxidant defense system to counteract the effects of free radicals. We explored the use of Malaysian Padina australis to attenuate high dose corticosterone-mediated oxidative damage in a cellular model mimicking depression. Fresh specimen of P. australis was freeze-dried and extracted sequentially with hexanes, ethyl acetate and ethanol. The extracts were screened for their phytochemical contents and antioxidant activities. Ethanol extract demonstrated the most potent antioxidant capacity and was selected for subsequent assays against high dose corticosterone of 600 µM-mediated oxidative damage in the rat pheochromocytoma (PC12) cells. The corticosterone reduced the cell viability, glutathione (GSH) level, aconitase activity, and mitochondrial membrane potential (MMP); and increased the lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) level and apoptosis. However, the extent of oxidative damage was reversed by 0.25-0.5 mg/mL ethanol extract suggesting a possible role of P. australis-based antioxidants in the mitochondrial defense against constant ROS generation and regulation of antioxidant pathway. The effects were similar to that of desipramine, a tricyclic antidepressant. Our findings indicate that P. australis can be developed as a mitochondria-targeted antioxidant to mitigate antidepressant-like effects.
    Matched MeSH terms: Membrane Potential, Mitochondrial
  17. Fulltext C-phycocyanin confers protection against oxalate-mediated oxidative stress and mitochondrial dysfunctions in MDCK cells
    Farooq SM, Boppana NB, Devarajan A, Asokan D, Sekaran SD, Shankar EM, et al.
    PLoS One, 2014;9(4):e93056.
    PMID: 24691130 DOI: 10.1371/journal.pone.0093056
    Oxalate toxicity is mediated through generation of reactive oxygen species (ROS) via a process that is partly dependent on mitochondrial dysfunction. Here, we investigated whether C-phycocyanin (CP) could protect against oxidative stress-mediated intracellular damage triggered by oxalate in MDCK cells. DCFDA, a fluorescence-based probe and hexanoyl-lysine adduct (HEL), an oxidative stress marker were used to investigate the effect of CP on oxalate-induced ROS production and membrane lipid peroxidation (LPO). The role of CP against oxalate-induced oxidative stress was studied by the evaluation of mitochondrial membrane potential by JC1 fluorescein staining, quantification of ATP synthesis and stress-induced MAP kinases (JNK/SAPK and ERK1/2). Our results revealed that oxalate-induced cells show markedly increased ROS levels and HEL protein expression that were significantly decreased following pre-treatment with CP. Further, JC1 staining showed that CP pre-treatment conferred significant protection from mitochondrial membrane permeability and increased ATP production in CP-treated cells than oxalate-alone-treated cells. In addition, CP treated cells significantly decreased the expression of phosphorylated JNK/SAPK and ERK1/2 as compared to oxalate-alone-treated cells. We concluded that CP could be used as a potential free radical-scavenging therapeutic strategy against oxidative stress-associated diseases including urolithiasis.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  18. Fulltext Subditine, a new monoterpenoid indole alkaloid from bark of Nauclea subdita (Korth.) Steud. induces apoptosis in human prostate cancer cells
    Liew SY, Looi CY, Paydar M, Cheah FK, Leong KH, Wong WF, et al.
    PLoS One, 2014;9(2):e87286.
    PMID: 24551054 DOI: 10.1371/journal.pone.0087286
    In this study, a new apoptotic monoterpenoid indole alkaloid, subditine (1), and four known compounds were isolated from the bark of Nauclea subdita. Complete (1)H- and (13)C- NMR data of the new compound were reported. The structures of isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS. All five compounds were screened for cytotoxic activities on LNCaP and PC-3 human prostate cancer cell-lines. Among the five compounds, the new alkaloid, subditine (1), demonstrated the most potent cell growth inhibition activity and selective against LNCaP with an IC50 of 12.24±0.19 µM and PC-3 with an IC50 of 13.97±0.32 µM, compared to RWPE human normal epithelial cell line (IC50 = 30.48±0.08 µM). Subditine (1) treatment induced apoptosis in LNCaP and PC-3 as evidenced by increased cell permeability, disruption of cytoskeletal structures and increased nuclear fragmentation. In addition, subditine (1) enhanced intracellular reactive oxygen species (ROS) production, as reflected by increased expression of glutathione reductase (GR) to scavenge damaging free radicals in both prostate cancer cell-lines. Excessive ROS could lead to disruption of mitochondrial membrane potential (MMP), release of cytochrome c and subsequent caspase 9, 3/7 activation. Further Western blot analyses showed subditine (1) induced down-regulation of Bcl-2 and Bcl-xl expression, whereas p53 was up-regulated in LNCaP (p53-wild-type), but not in PC-3 (p53-null). Overall, our data demonstrated that the new compound subditine (1) exerts anti-proliferative effect on LNCaP and PC-3 human prostate cancer cells through induction of apoptosis.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  19. Fulltext Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L.) seeds
    Looi CY, Arya A, Cheah FK, Muharram B, Leong KH, Mohamad K, et al.
    PLoS One, 2013;8(2):e56643.
    PMID: 23437193 DOI: 10.1371/journal.pone.0056643
    Centratherum anthelminticum (L.) seeds (CA) is a well known medicinal herb in Indian sub-continent. We recently reported anti-oxidant property of chloroform fraction of Centratherum anthelminticum (L.) seeds (CACF) by inhibiting tumor necrosis factor-α (TNF-α)-induced growth of human breast cancer cells. However, the active compounds in CACF have not been investigated previously.
    Matched MeSH terms: Membrane Potential, Mitochondrial/drug effects
  20. 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: Membrane Potential, Mitochondrial/drug effects
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