• The Korean Journal of Physiology and Pharmacology
• /
• v.12 no.2
• /
• pp.65-71
• /
• 2008

The present study examined the inhibitory effect of licorice compounds glycyrrhizin and a metabolite $18{\beta}$-glycyrrhetinic acid on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse and on the 1-methyl-4-phenylpyridinium ($MPP^+$)-induced cell death in differentiated PC12 cells. MPTP treatment increased the activities of total superoxide dismutase, catalase and glutathione peroxidase and the levels of malondialdehyde and carbonyls in the brain compared to control mouse brain. Co-administration of glycyrrhizin (16.8 mg/kg) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. In vitro assay, licorice compounds attenuated the $MPP^+$-induced cell death and caspase-3 activation in PC12 cells. Glycyrrhizin up to $100{\mu}M$ significantly attenuated the toxicity of $MPP^+$. Meanwhile, $18{\beta}$-glycyrrhetinic acid showed a maximum inhibitory effect at $10{\mu}M$; beyond this concentration the inhibitory effect declined. Glycyrrhizin and $18{\beta}$-glycyrrhetinic acid attenuated the hydrogen peroxide- or nitrogen species-induced cell death. Results from this study indicate that glycyrrhizin may attenuate brain tissue damage in mice treated with MPTP through inhibitory effect on oxidative tissue damage. Glycyrrhizin and $18{\beta}$-glycyrrhetinic acid may reduce the $MPP^+$ toxicity in PC12 cells by suppressing caspase-3 activation. The effect seems to be ascribed to the antioxidant effect.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.4
• /
• pp.1471-1476
• /
• 2012

Background and Aim: Currently available systemic therapies for malignant melanoma produce low response rates in patients, and more effective treatment modalities are clearly needed. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand has a significant impact on therapy for patients with X-linked inhibitor of apoptosis protein-downregulation malignant melanoma. The primary objective of this study was to assess its therapeutic potential. Materials and Methods: We employed a conditionally replicating oncolytic adenoviral vector, named CRAd5.TRAIL/siXIAP, with the characteristics of over-expression of the therapeutic gene TRAIL and downregulation of XIAP in one vector. B16F10-luc cells were employed to detect anti-tumor activity of CRAd5.TRAIL/siXIAP in vitro and in vivo. Results: CRAd5.TRAIL/siXIAP enhanced caspase-8 activation and caspase-3 maturation in B16F10 cells in vitro. Furthermore, it more effectively infected and killed melanoma cells in vitro and in vivo than other adenoviruses. Conclusion: Taken together, the combination of upregulation of TRAIL and downregulation of siXIAP with one oncolytic adenoviral vector holds promise for development of an effective therapy for melanomas and other common cancers.

• Biomolecules & Therapeutics
• /
• v.12 no.1
• /
• pp.9-18
• /
• 2004

Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of ${\beta}$-carbolines (harmaline and harmalol) and deprenyl on the dopamine-induced change in the mitochondrial membrane permeability and cell death in differentiated PC12 cells. Cell death due to 250 4{\mu}$M dopamine was inhibited by caspase inhibitors (z-IETD.fmk, z-LEHD.fmk and z-DQMD.fmk) and antioxidants (N-acetylcysteine, ascorbate, superoxide dismutase, catalase and carboxy-PTIO). ${\beta}$-Carbolines prevented the dopamine-induced cell death in PCl2 cells, while deprenyl did not inhibit cell death. ${\beta}$-Carbolines decreased the condensation and fragmentation of nuclei caused by dopamine in PC12 cells. ${\beta}$-Carbolines inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, formation of reactive oxygen species and depletion of GSH caused by dopamine in PC12 cells, whereas deprenyl did not decrease dopamine-induced mitochondrial damage. ${\beta}$-Carbolines, deprenyl and antioxidants depressed the formation of nitric oxide and melanin in dopamine-treated PC12 cells. The results suggest that cell death due to dopamine PC12 cells is mediated by caspase-8, -9 and -3. Unlike deprenyl, ${\beta}$-carbolines may attenuate the dopamineinduced cell death in PC12 cells by suppressing change in the mitochondrial membrane permeability through inhibition of the toxic action of reactive oxygen and nitrogen species.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.7
• /
• pp.3073-3076
• /
• 2012

Terpinen-4-ol is a terpene found in the rhizome of Plai (Zingiber montanum (Koenig) Link ex Dietr.). In this study apoptogenic activity and mechanisms of cell death induced by terpinen-4-ol were investigated in the human leukemic MOLT-4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with characteristic morphological features of apoptosis by Wright's staining. The mode of cell death was confirmed to be apoptosis by flow cytometric analysis after staining with annexin V-FITC and propidium iodide. A sub-G1 peak in DNA histograms of cell cycle assays was observed. Terpinen-4-ol induced-MOLT-4 cell apoptosis mediated through an intrinsic pathway involving the loss of mitochondrial transmembrane potential (MTP) and release of cytochrome c into the cytosol. In addition, terpinen-4-ol also induced apoptosis via an extrinsic pathway by caspase-8 activation resulting in the cleavage of cytosolic Bid. Truncated-Bid (tBid) translocated to mitochondria and activated the mitochondrial pathway in conjunction with down-regulation of Bcl-2 protein expression. Caspase-3 activity also increased. In conclusion, terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.3
• /
• pp.1169-1173
• /
• 2015

Background: Paris polyphylla (Chinese name: Chonglou) had been traditionally used for a long time and shown anti-cancer action. Based on the previous study that paris polyphylla steroidal saponins (PPSS) induced cytotoxic effect in human lung cancer A549 cells, this study was designed to further illustrate the mechanisms underlying. Materials and Methods: The mechanisms involved in PPSS-induced A549 cell death were investigated by phase contrast microscopy and fluorescence microscopy, flow cytometry and western blot analysis, respectively. Results: PPSS decreased the proportion of viable A549 cells, and exposure of A549 cells to PPSS led to both apoptosis and autophagy. Apoptosis was due to activations of caspase-8, caspase-3, as well as cleavage of PARP, and autophagy was confirmed by up-regulation of Beclin 1 and the conversion from LC3 I to LC3 II. Conclusions: PPSS was able to induce lung cancer A549 cell apoptosis and autophagy in vitro, the results underlining the possibility that PPSS would be a potential candidate for intervention against lung cancer.

• The Journal of Korean Medicine
• /
• v.22 no.4
• /
• pp.45-57
• /
• 2001

Objectives : The water extract of Gwibitang (GBT) has been traditionally used for treatment of psychologic disease and brain damage in Oriental Medicine, This study was designed to investigate the effect of GBT on the glutamate-induced toxicity of rat C6 glial cells. Methods : The cultured cells were pretreated with GBT and exposed to glutamate, The cell damage was assessed by using MTT assay and Hoechst, IC-l staining, Results : GBT had protective effects in glutamate-induced cytotoxicity, which was revealed as apoptosis characterized by chromatic condensation and the loss of mitochondrial membrane potential in C6 glial cells. However, GBT and glutamate had no effect in the activation of caspase family cysteine proteases including caspase-3, -8 and -9 proteasesin C6 glial ce]]s, GBT significantly recovered the depletion of GSH and inhibited the generation of $H_2O_2$ by glutamate in C6 glial cells. In addition, both GBT and antioxidants such as GSH and NAC protected the glutamate-induced cytotoxicity in C6 glial cells, indicating that GBT possibly has antioxidative effect. Moreover, GBT also inhibited the glutamate-induced degradation of $IkB{\alpha}$ in C6 glial cells, This result suggest that GBT has some inhibitory effects on the transcriptional activation of $NF-_{k}B$. Conclusions : GBT has protective effects in glutamate-induced cytotoxicity via an antioxidative mechanism.

• Biomolecules & Therapeutics
• /
• v.24 no.1
• /
• pp.49-56
• /
• 2016

To determine the protective effect of aloe-emodin (AE) from high glucose induced toxicity in RIN-5F (pancreatic ${\beta}$-cell) cell and restoration of its function was analyzed. RIN-5F cells have been cultured in high glucose (25 mM glucose) condition, with and without AE treatment. RIN-5F cells cultured in high glucose decreased cell viability and increased ROS levels after 48 hr compared with standard medium (5.5 mM glucose). Glucotoxicity was confirmed by significantly increased ROS production, increased pro-inflammatory (IFN-${\gamma}$, IL-$1{\beta}$,) & decreased anti-inflammatory (IL-6&IL-10) cytokine levels, increased DNA fragmentation. In addition, we found increased Bax, caspase 3, Fadd, and Fas and significantly reduced Bcl-2 expression after 48 hr. RIN-5F treated with both high glucose and AE ($20{\mu}M$) decreased ROS generation and prevent RIN-5F cell from glucotoxicity. In addition, AE treated cells cultured in high glucose were transferred to standard medium, normal responsiveness to glucose was restored within 8hr and normal basal insulin release within 24 hr was achieved when compared to high glucose.

• Journal of Acupuncture Research
• /
• v.30 no.1
• /
• pp.43-55
• /
• 2013

I investigated whether snake venom toxin(SVT) from Vipera lebetina turanica enhances the apoptosis ability of tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) in cancer cells. TRAIL inhibited HCT116 cell growth in a dose-dependent manner. Consistent with cell growth inhibition, the expression of TRAIL receptors; DR4 and DR5 was significantly increased as well as apoptosis related proteins such as cleaved caspase-3, 8, 9 and Bax. However, the expression of survival proteins(eg, cFLIP, survivin, XIAP and Bcl2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the reactive oxygen species(ROS) scavenger N-acetylcysteine reduced the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the apoptosis related protein such as caspase-3 and-9 as well as cell growth inhibitory effects. The collective results suggest that SVT facilitates TRAIL-induced apoptosis in human colorectal cancer HCT116 cells through up-regulation of the TRAIL receptors; DR4 and DR5 via ROS pathway signals.

• Microbiology and Biotechnology Letters
• /
• v.47 no.1
• /
• pp.43-53
• /
• 2019

The anticancer activity of guava (Psidium guajava L.) leaf extract (GLE) occurs via the induction of apoptosis in cancer cells. However, the mechanism behind GLE-induced apoptosis in the human hepatocellular carcinoma cell line HepG2 remains unclear. In the present study, we investigated the apoptotic effects and mechanism of action of GLE in cultured HepG2 cells. The results showed that GLE induced reactive oxygen species (ROS) synthesis and disrupted the mitochondrial membrane potential (${\Delta}{\Psi}m$). Moreover, GLE increased the expression of apoptotic pathway proteins, such as the cleaved forms of caspase-3, -8, and -9; the translocation of Bax and cytochrome c (cyt-c) from the mitochondria to the cytosol; and the downregulation of Bcl-2. In addition, p53 protein expression was increased upon GLE treatment. These observations indicate that the GLE-induced apoptosis in HepG2 cells is mediated by mitochondrial ROS generation, followed by caspase activation and cyt-c release, suggesting that GLE may be a promising candidate for the development of novel drugs for the treatment of liver cancers.

• The Korean Journal of Food And Nutrition
• /
• v.35 no.3
• /
• pp.204-212
• /
• 2022

The purpose of this study was to investigate the biological activity of fucoidan, a sulfur-containing polysaccharide, on cytotoxicity and apoptosis in the human HT-29 colorectal cancer cell line using cell viability, Flow cytometry, Western blot, and RT-PCR analyses. Fucoidan inhibited the proliferation of HT-29 cells by 39.6% at a concentration of 100 ㎍/mL for 72 h. The inhibition was dose-dependent and accompanied by apoptosis. Flow cytometric analysis showed that fucoidan increased early apoptosis and late apoptosis by 65.84% and 72.09% at concentrations of 25 and 100 ㎍/mL, respectively. Analysis of the mechanism of these events indicated that fucoidan-treated cells exhibited increases in the activation of caspase-3, caspase-8, and PARP in a dose-dependent manner. These results suggest that fucoidan may inhibit the growth of human colorectal cancer cells by various apoptosis-promoting effects, as well as by apoptosis itself.