• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.1
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• pp.26-32
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• 2012

Purified salt and several different types of sea salts showed comutagenicity in the presence of MNNG (N-methyl-N'-nitro-N-nitrosoguanidine). However, the salts exhibited anti-cancer effects in HCT-116 human colon carcinoma cells and AGS human gastric adenocarcinoma cells. Sea salt showed less comutagenicity effects than purified salt. French sea salt (Salines de Guerande) and Korean sea salt I, which contained higher levels of minerals, showed less comutagenicity. In MTT assay, when HCT-116 and AGS cancer cells were treated with the salts, French sea salt (36% and 34%) and Korean sea salt I (35% and 33%) showed higher anticancer activities than Spanish sea salt (33% and 31%), Italian sea salt (29% and 27%), Korean sea salt II (22% and 22%), or purified salt (18% and 15%) at a salt concentration of 1%. French sea salt and Korean sea salt I also showed better anticancer activities than the other salt samples at a low concentration of 0.5% (p<0.05). Apoptosis related genes of Bax and Bcl-2 were regulated by the treatment of the salt in the colon cancer cells. French sea salt and Korean sea salt I especially increased Bax mRNA expression, but decreased Bcl-2 expression, indicating that they can induce apoptosis of the cancer cells. From the experimental results, sea salt showed better health functional effects than the purified salt, and French sea salt and Korean sea salt I which contained high levels of Ca, K, and Mg showed better effects.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1513-1519
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• 2007

Yukwool-tang (YWT) is a traditional Chinese medicine, which has been used for patients suffering from a uterine disease in Oriental medicine. In the present study, it was examined the biochemical mechanisms of apoptosis by YWT in human cervical carcinoma HeLa cells. It was found that YWT could inhibit the cell growth of HeLa cells in a dose-dependent manner, which was associated with apoptotic cell death such as formation of apoptotic bodies and DNA fragmentation. Flow cytometry analysis confirmed that YWT treatment increased populations of apoptotic-sub-G1 phase of the cell cycle. We observed the p53-independent induction of p21 proteins, down-regulation of anti apoptotic Bcl-2 expression and proteolytic activation of caspase-3 in YWT-treated HeLa cells. YWT treatment also concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), phospholipase C-1 ($PLC{\gamma}1$), ${\beta}-catenin$ and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Taken together, these findings partially provide novel insights into the possible molecular mechanism of the anti-cancer activity of YWT.

• Journal of Microbiology and Biotechnology
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• v.28 no.4
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• pp.542-550
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• 2018

Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88-1) with the non-benzoquinone skeleton, obtained from genetically engineered Streptomyces hygroscopicus, was found to have anticancer activity against two human breast cancer cell lines. WK-88-1 produced concentration-dependent inhibition of cell proliferation, cell cycle arrest, and apoptosis in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cell lines. Detailed analysis showed that WK-88-1 downregulated some key cell cycle molecules (CDK1 and cyclin B1) and lead to $G_2/M$ cell cycle arrest. Further studies also showed that WK-88-1 could induce human breast cancer cell apoptosis by downregulating Hsp90 client proteins (Akt, p-Akt, IKK, c-Raf, and Bcl-2), decreasing the ATP level, increasing reactive oxygen species production, and lowering the mitochondrial membrane potential. Meanwhile, we discovered that WK-88-1 significantly decreased the levels of Her-2 and $ER-{\alpha}$ in MCF-7 cells but not in MDA-MB-231 cells. In addition, WK-88-1 significantly increased caspase-3, -8, and -9 activities and the cleavage of PARP in a concentration-dependent manner (with the exception of caspase-3 and PARP in MCF-7 cells). Taken together, our preliminary results suggest that WK-88-1 has the potential to play a role in breast cancer therapy.

• Bulletin of the Korean Chemical Society
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• v.21 no.7
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• pp.720-726
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• 2000

The analytic gradient method for the equation-of-motion coupled-cluster singles and doubles (EOM-CCSD) energy has been extended to employ a reduced molecular orbital (MO) space. Not only the innermost core MOs but also some of the outermost virtua l MOs can be dropped in the reduced MO space, and a substantial amount of computation time can be reduced without deteriorating the results. In order to study the magnitudes and trends of the effects of the dropped MOs, the geometries and vibrational properties of the ground and excited states of BF, CO, CN, N2, AlCl, SiS, P2, BCl, AIF, CS, SiO, PN and GeSe are calculated with different sizes of molecular orbital space. The 6-31 G* and the aug-cc-pVTZ basis sets are employed for all molecules except GeSc for which the 6-311 G* and the TZV+f basis sets are used. It is shown that the magnitudes of the drop-MO effects are about $0.005\AA$ in bond lengths and about 1% on harmonic frequencies and IR intensities provided that the dropped MOs correspond to (1s), (1s,2s,2p), an (1s,2s,2p,3s,3p) atomic orbitals of the first, the second, and the third row atoms, respectively. The geometries and vibrational properties of the first and the second excited states of HCN and HNC are calculated by using a drastically reduced virtual MO space as well as with the well defined frozen core MO space. The results suggest the possibility of using a very smalI MO space for qualitative study of valence excited states.

• Nutrition Research and Practice
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• v.14 no.1
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• pp.3-11
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• 2020

BACKGROUND/OBJECTIVES: Oxidative stress causes cell damage and death, which contribute to the pathogenesis of neurodegenerative diseases. Urolithin A (UA), a gut microbial-derived metabolite of ellagitannins and ellagic acid, has high bioavailability and various health benefits such as antioxidant and anti-inflammatory effects. However, it is unknown whether it has protective effects against oxidative stress-induced cell death. We investigated whether UA ameliorates H₂O₂-induced neuronal cell death. MATERIALS/METHODS: We induced oxidative damage with 300 μM H₂O₂ after UA pretreatment at concentrations of 1.25, 2.5, and 5 μM in SK-N-MC cells. Cytotoxicity and cell viability were determined using the CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using a 2,7-dichlorofluorescein diacetate assay. Hoechst 33342 staining was used to characterize morphological changes in apoptotic cells. The expressions of apoptosis proteins were measured using Western blotting. RESULTS: UA significantly increased cell viability and decreased intracellular ROS production in a dose-dependent manner in SK-N-MC cells. It also decreased the Bax/Bcl-2 ratio and the expressions of cytochrome c, cleaved caspase-9, cleaved caspase-3, and cleaved PARP. In addition, it suppressed the phosphorylation of the p38 mitogen-activated protein kinase (MAPK) pathway. CONCLUSIONS: UA attenuates oxidative stress-induced apoptosis via inhibiting the mitochondrial-related apoptosis pathway and modulating the p38 MAPK pathway, suggesting that it may be an effective neuroprotective agent.

• Journal of Veterinary Clinics
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• v.28 no.6
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• pp.549-554
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• 2011

FK506 is a widespread immunosuppressive drug after liver transplantion in patients with advanced-stage hepatocellular carcinoma. Dexamethasone is frequently used as co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. Our aim was to investigate antitumor effects of FK506 in Hep3B cells, one of differentiated human hepatocellular carcinoma cell lines and inhibitory effects of dexamethsone on FK506- induced antitumor effects. Cell injury was evaluated by biochemical assays as cell viability, lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in Hep3B cells. Intracellular calcium concentration ([$Ca^{2+}$]i) and the level of activation of the c-Jun-N-terminal kinase (JNK) and the Bax protein in cultured Hep3B cells was measured. Exposure of 0.1 ${\mu}M$ FK506 to Hep3B cells led to cell death accompanied by a decrease in cell viability and an increase in LDH, ROS and [$Ca^{2+}$]i. FK506 induced an increase in activity of Bax and JNK protein but inhibited the activity of Bcl-2 protein. Treatment of dexamethsone, per se, had no effects on cell viability, LDH and ROS. However, co-treatment of FK506 and dexamethasone diminished the FK506-induced LDH release, ROS generation and JNK activation. These results demonstrate that FK506 has antitumor effect in Hep3B cells but the combination of FK506 and dexamethasone antagonizes the FK506-induced antitumor effects.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.175-181
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• 2018

Carbon monoxide (CO) is well-known as toxic gas and intrinsic signaling molecule such as neurotransmitter and blood vessel relaxant. Recently, it has been reported that low concentration of CO exerts therapeutic actions under various pathological conditions including liver failure, heart failure, gastric cancer, and cardiac arrest. However, little has been known about the effect of CO in neurodegenerative diseases like Parkinson's disease (PD). To test whether CO could exert a beneficial action during oxidative cell death in PD, we examined the effects of CO on 6-hydroxydopamine (6-OHDA)-induced cell death in C6 glioma cells. Treatment of CO-releasing molecule-2 (CORM-2) significantly attenuated 6-OHDA-induced apoptotic cell death in a dose-dependent manner. CORM-2 treatment decreased Bax/Bcl2 ratio and caspase-3 activity, which had been increased by 6-OHDA. CORM-2 increased phosphorylation of NF-E2-related factor 2 (Nrf2) which is a transcription factor regulating antioxidant proteins. Subsequently, CORM-2 also increased the expression of heme oxygenase-1 and superoxide dismutases (CuZnSOD and MnSOD), which were antioxidant enzymes regulated by Nrf2. These results suggest that CO released by CORM-2 treatment may have protective effects against oxidative cell death in PD through the potentiation of cellular adaptive survival responses via activation of Nrf2 and upregulation of heme oxygenase-1, leading to increasing antioxidant defense capacity.

• Journal of Life Science
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• v.25 no.11
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• pp.1331-1337
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• 2015

S-allylcysteine (SAC) is an aged garlic derived water soluble organosulfur compound and has been suggested to have anticarcinogenic activity against diverse types of cancer cells. This review summarizes the cellular signaling pathways and molecular mechanisms whereby SAC exerts its effects on cellular proliferation, apoptosis, cell cycle progression and metastasis based on the results from both in vitro and in vivo studies. SAC activates proapoptotic proteins including Bax and caspase-3, but suppresses antiapoptotic Bcl-2 family proteins to bring about cancer cell death through mitochondria-mediated intrinsic pathway. SAC also inhibits cellular proliferation by inducing cell cycle arrest in which SAC reduces expression and activation of NF-κB, cyclins, Cdks, PCNA and c-Jun, but elevates expression of cell cycle inhibitor proteins p16 and p21 through suppression of both PI3K/Akt/mTOR and MAPK/ERK signaling pathways. And, SAC inhibits invasion and metastasis of cancer cells by inducing suppression of both angiogenesis and epithelial-mesenchymal transition (EMT) through decreased cyclooxygenase (COX)-2 expression and increased E-cadherin expression which were then caused by suppression of inhibitory transcription factors Id-1 and SLUG from SAC-mediated inactivation of both MAPK/ERK and PI3K/Akt/mTOR/NF-κB signaling pathways. Furthermore, SAC prevents toxic compound-induced carcinogenesis by inducing antioxidant enzymes such as glutathione-s-transferase (GST). Thus, SAC can be considered as a potential chemotherapeutic agent for the prevention and treatment of cancer.

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

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.503-511
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• 2018

Triclosan (TCS) and bisphenol A (BPA) are endocrine-disrupting chemicals that interfere with the hormone or endocrine system and may cause cancer. Kaempferol (Kaem) and 3,3'-diindolylmethane (DIM) are phytoestrogens that play chemopreventive roles in the inhibition of carcinogenesis and cancer progression. In this study, the influence of TCS, BPA, Kaem, and DIM on proliferation and apoptotic abilities of VM7Luc4E2 breast cancer cells were examined. MTT assay revealed that TCS ($0.1-10{\mu}M$), BPA ($0.1-10{\mu}M$) and E2 ($0.01-0.0001{\mu}M$) induced significant cell proliferation of VM7Luc4E2 cells, which was restored to the control (0.1% DMSO) by co-treatment with Kaem ($30{\mu}M$) or DIM ($15{\mu}M$). Reactive oxygen species (ROS) production assays showed that TCS and BPA inhibited ROS production of VM7Luc4E2 cells similar to E2, but that co-treatment with Kaem or DIM on VM7Luc4E2 cells induced increased ROS production. Based on these results, the effects of TCS, BPA, Kaem, and DIM on protein expression of apoptosis and ROS production-related markers such as Bax and Bcl-xl, as well as endoplasmic reticulum (ER) stress-related markers such as $eIF2{\alpha}$ and CHOP were investigated by Western blot assay. The results revealed that TCS, and BPA induced anti-apoptosis by reducing ROS production and ER stress. However, Kaem and DIM effectively inhibited TCS and BPA-induced anti-apoptotic processes in VM7Luc4E2 cells. Overall, TCS and BPA were revealed to be distinct xenoestrogens that enhanced proliferation and anti-apoptosis, while Kaem and DIM were identified as natural chemopreventive compounds that effectively inhibited breast cancer cell proliferation and increased anti-apoptosis induced by TCS and BPA.