• Journal of Physiology & Pathology in Korean Medicine
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• 제21권6호
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• pp.1437-1449
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• 2007

In this study, the effect of extract of Corydalis yanhusuo (ECT) used in Oriental medicine therapy was investigated on the cell growth and apoptosis of HepG2 human hepatoma cells. It was found that ECT could inhibit the cell growth effectively in a dose-dependent manner, which was associated with morphological change and apoptotic cell death such as formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase. And we observed the effects of ECT on loss of mitochondrial membrane potential (MMP), using the JC-1 probe by DNA flow cytometric analysis. Apoptosis of HepG2 cells by ECT was associated with a down-regulation of anti apoptotic Bcl-2 expression, inhibitor of apoptosis proteins (IAPs) expression and proteolytic activation of caspase-3 and caspase-9. However, ECT did not affect the pro-apoptotic Bax expression and activity of caspase-8. ECT treatment also concomitant degradation and /or inhibition of poly (ADP-ribose) polymerase (PARP), phospholipase C-1 ($PLC{\gamma}1$). Furthermore, ECT treatment caused a dose-dependent inhibition of iNOS and cyclooxygenase-2 (Cox-2). Additionally ECT have been implicated in the regulation of telomerase expression. ECT treatment induced the down-regulation of telomerase reverse transcriptase mRNA (hTERT) expression of HepG2 cells. Taken together, these findings suggest that ECT may be a potential chemotherapeutic agent for the control of HepG2 human hepatoma cells.

• The Korean Journal of Physiology and Pharmacology
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• 제22권6호
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• pp.689-696
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• 2018

Increasing evidence implicates changes in $[Ca^{2+}]_i$ and oxidative stress as causative factors in amyloid beta ($A{\beta}$)-induced neuronal cell death. Cyanidin-3-glucoside (C3G), a component of anthocyanin, has been reported to protect against glutamate-induced neuronal cell death by inhibiting $Ca^{2+}$ and $Zn^{2+}$ signaling. The present study aimed to determine whether C3G exerts a protective effect against $A{\beta}_{25-35}$-induced neuronal cell death in cultured rat hippocampal neurons from embryonic day 17 fetal Sprague-Dawley rats using MTT assay for cell survival, and caspase-3 assay and digital imaging methods for $Ca^{2+}$, $Zn^{2+}$, MMP and ROS. Treatment with $A{\beta}_{25-35}$ ($20{\mu}M$) for 48 h induced neuronal cell death in cultured rat pure hippocampal neurons. Treatment with C3G for 48 h significantly increased cell survival. Pretreatment with C3G for 30 min significantly inhibited $A{\beta}_{25-35}$-induced $[Zn^{2+}]_i$ increases as well as $[Ca^{2+}]_i$ increases in the cultured rat hippocampal neurons. C3G also significantly inhibited $A{\beta}_{25-35}$-induced mitochondrial depolarization. C3G also blocked the $A{\beta}_{25-35}$-induced formation of ROS. In addition, C3G significantly inhibited the $A{\beta}_{25-35}$-induced activation of caspase-3. These results suggest that cyanidin-3-glucoside protects against amyloid ${\beta}$-induced neuronal cell death by reducing multiple apoptotic signals.

• Journal of Life Science
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• 제27권1호
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• pp.78-88
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• 2017

Angiogenesis, the formation of new blood vessels, plays an important role in tumor growth and metastasis; therefore, it has become an important target in cancer therapy. Novel anticancer pharmaceutical products that have relatively few side effects or are non-cytotoxic must be developed, and such products may be obtained from traditional herbal medicines. Coptis chinensis Franch. is an herb used in traditional medicine for the treatment of inflammatory diseases and diabetes. However, potential antiangiogenic effects of C. chinensis water extract (CCFWE) have not yet been studied. The purpose of this study was to determine the antiangiogenic effect of CCFWE in order to evaluate its potential for an anticancer drug. We found that the treatment with CCFWE inhibited the major steps of the angiogenesis process, such as the endothelial cell proliferation, migration, invasion, and capillary-like tube formation in response to vascular endothelial growth factor (VEGF), and also resulted in the growth inhibition of new blood vessels in an ex vivo rat aortic ring assay. We also observed that CCFWE treatment arrested the cell cycle at the G0/G1 phase, preventing the G0/G1 to S phase cell cycle progression in response to VEGF. In addition, the treatment reduced the VEGF-induced activation of matrix metalloproteinases 2 and 9. Taken together, these findings indicate that CCFWE should be considered a potential anticancer therapy against pathological conditions where angiogenesis is stimulated during tumor development.

• The Korea Journal of Herbology
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• 제30권1호
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• pp.67-75
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• 2015

Objectives : The aim of this study is to examine the neuroprotective effect of wheat bran extract (WBE) against ${\beta}$-amyloid ($A{\beta}$)-induced apoptotic cell death in SH-SY5Y human neuroblastoma cells and memory impairment in triple transgenic animal model's of Alzheimer's disease (3xTg AD mice). Methods : In SH-SY5Y cells, MTT assay and TUNEL staining were conducted to evaluate the protective effect of WBE against $A{\beta}_{25-35}$-induced neurotoxicity and apoptosis. Alterations in mitochondrial transmembrane potential (MMP), expression of proapoptotic Bax and antiapoptotic Bcl-2 proteins, cleavage of PARP, and brain-derived neurotrophic factor (BDNF) levels were analyzed to elucidate the neuroprotective mechanism of WBE. To further investigate the memory enhancing effect of WBE, Morris water maze test was performed in 3xTg AD mice. Results : In SH-SY5Y cells, WBE protected against $A{\beta}_{25-35}$-caused cytotoxicity and apoptosis as shown by the restoration of cell viability in MTT assay and inhibition of DNA fragmentation in TUNEL staining. $A{\beta}_{25-35}$-induced apoptotic signals such as dissipation of MMP, decreased Bcl-2/Bax ratio, and cleavage of PARP were suppressed by WBE. Moreover, WBE up-regulated the protein levels of BDNF, which seemed to be mediated by activation of cAMP response element-binding protein (CREB). In 3xTg AD mice, oral administration of WBE attenuated learning and memory deficit as verified by reduced mean escape latency in water maze test. Conclusions : WBE protects neuronal cells from $A{\beta}_{25-35}$-induced apoptotic cell death and restores learning and memory impairments in 3xTg AD mice. These findings suggest that WBE exhibit neuroprotective potential for the management of AD.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.625-633
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• 2017

Sphingosylphosphorylcholine (SPC) is one of the bioactive phospholipids that has many cellular functions such as cell migration, adhesion, proliferation, angiogenesis, and $Ca^{2+}$ signaling. Recent studies have reported that SPC induces invasion of breast cancer cells via matrix metalloproteinase-3 (MMP-3) secretion leading to WNT activation. Thrombospondin-1 (TSP-1) is a matricellular and calcium-binding protein that binds to a wide variety of integrin and non-integrin cell surface receptors. It regulates cell proliferation, migration, and apoptosis in inflammation, angiogenesis and neoplasia. TSP-1 promotes aggressive phenotype via epithelial mesenchymal transition (EMT). The relationship between SPC and TSP-1 is unclear. We found SPC induced EMT leading to mesenchymal morphology, decrease of E-cadherin expression and increases of N-cadherin and vimentin. SPC induced secretion of thrombospondin-1 (TSP-1) during SPC-induced EMT of various breast cancer cells. Gene silencing of TSP-1 suppressed SPC-induced EMT as well as migration and invasion of MCF10A cells. An extracellular signal-regulated kinase inhibitor, PD98059, significantly suppressed the secretion of TSP-1, expressions of N-cadherin and vimentin, and decrease of E-cadherin in MCF10A cells. ERK2 siRNA suppressed TSP-1 secretion and EMT. From online PROGgene V2, relapse free survival is low in patients having high TSP-1 expressed breast cancer. Taken together, we found that SPC induced EMT and TSP-1 secretion via ERK2 signaling pathway. These results suggests that SPC-induced TSP-1 might be a new target for suppression of metastasis of breast cancer cells.

• Proceedings of the Plant Resources Society of Korea Conference
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• 한국자원식물학회 2023년도 임시총회 및 춘계학술대회
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• pp.50-50
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• 2023

Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• KSBB Journal
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• 제27권5호
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• pp.289-294
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• 2012

Resveratrol, natural polyphenol in grapes and red wine, is known to have the anti-proliferatory and anti-angiogenic effects in various cancer cells. In this study, we have investigated the effects of resveratrol in HT-29 colon cancer cells. Treatment of resveratrol in different concentrations and time inhibited proliferation of HT-29 colon cancer cells. We explored the effects of resveratrol on HT-29 colon cancer cell motility using a wound healing assay. In the absence of the resveratrol, the HT-29 cells are migrated along the edges of the wound and showed a large-scale migration, whereas dose- and time-dependent inhibition of cell flattening and spreading was observed in the presence of resveratrol. Resveratrol inhibited MMP-9 in a dose- and time-dependent on HT-29 colon cancer cells by Western blotting. In addition, resveratrol increased AMPK activity and decreased COX-2, VASP and VEGF expression. Treatment of compound C inhibited AMPK activity, however, the expression of VASP and COX-2 increased thus, COX-2 and VASP are modulated by AMPK. However treatment of celecoxib could not control AMPK activity but decreased VEGF expression. We suggest that resveratrol inhibits cell proliferation and migration through activation of AMPK and decreased COX-2, VASP and VEGF expression in HT-29 colon cancer cells.

• Journal of Life Science
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• 제24권12호
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• pp.1345-1355
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• 2014

The interruption of angiogenesis using herbal extracts is now recognized as a useful approach for treating many solid tumors. To date, the best-validated antitumor approach is to target the vascular endothelial growth factor (VEGF)-induced angiogenic pathway. In the present study, we first identified the antiangiogenic activity of a hot-water extract of Rubus coreanus Miquel (RCMHE) in vitro and ex vivo. This extract suppressed VEGF-induced angiogenesis, the phosphorylation of extracellular regulated kinase (ERK), p38 and the activation of matrix metalloproteinases (MMPs). RCMHE also inhibited the VEGF-responsive phosphorylation of VEGFR2. These results clearly show that RCMHE may have potential therapeutic value for angiogenesis-associated human diseases through the suppression of angiogenesis and the interruption of the phosphorylation of VEGFR2.

• Korean Journal of Plant Resources
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• 제32권4호
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• pp.255-263
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• 2019

Glycyrrhizae radix is one of the most frequently prescribed ingredients in Oriental medicine, and Glycyrrhizae radix extract has been shown to exert anti-cancer effects. However, the cellular and molecular mechanisms of programed cell death (apoptosis) by Glycyrrhizae radix are poorly defined. In the present study, it was examined the molecular mechanisms of apoptosis by water extracts of Glycyrrhizae radix (GRW) in human bladder T24 cancer cells. It was found that GRW could inhibit the cell growth of T24 cells in a concentration-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, DNA fragmentation and increased populations of annexin-V positive cells. The induction of apoptotic cell death by GRW was connected with an up-regulation of pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic proteins (Bcl-2 and Bcl-xL), and inhibition of apoptosis family proteins (XIAP, cIAP-1 and cIAP-2). In addition, apoptosis-inducing concentrations of GRW induced the activation of caspase-9, an initiator caspase of the mitochondrial-mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of PARP. GRW also induced apoptosis via a death receptor-mediated extrinsic pathway by caspase-8 activation, resulting in the down-regulation of total Bid and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. Taken together, the present results suggest that GRW may be a potential chemotherapeutic agent for the control of human bladder cancer cells.

• Journal of Ginseng Research
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• 제41권4호
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• pp.456-462
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• 2017

Background: Abnormal activation of matrix metalloproteinases (MMPs) plays an important role in UV-induced wrinkle formation, which is a major dermatological problem. This formation occurs due to the degeneration of the extracellular matrix (ECM). In this study, we investigated the cutaneous photoprotective effects of Ultraflo L treated ginseng leaf (UTGL) in hairless mice. Methods: SKH-1 hairless mice (6 weeks of age) were randomly divided into four groups (8 mice/group). UTGL formulation was applied topically to the skin of the mice for 10 weeks. The normal control group received nonvehicle and was not irradiated with UVB. The UV control (UVB) group received nonvehicle and was exposed to gradient-UVB irradiation. The groups (GA) receiving topical application of UTGL formulation were subjected to gradient-UVB irradiation on $0.5mg/cm^2$ [GA-low (GA-L)] and $1.0mg/cm^2$ [(GA-high (GA-H)] of dorsal skin area, respectively. Results: We found that topical treatment with UTGL attenuated UVB-induced epidermal thickness and impairment of skin barrier function. Additionally, UTGL suppressed the expression of MMP-2, -3, and -13 induced by UVB irradiation. Our results show that topical application of UTGL protects the skin against UVB-induced damage in hairless mice and suggest that UTGL can act as a potential agent for preventing and/or treating UVB-induced photoaging. Conclusion: UTGL possesses sunscreen properties and may exhibit photochemoprotective activities inside the skin of mice. Therefore, UTGL could be used as a potential therapeutic agent to protect the skin against UVB-induced photoaging.