• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1089-1097
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• 2004

This study was designed to elucidate the synergistic cytotoxic mechanisms of the cotreatment of Gagamsibjeondaebo-tang (GSD) and AS₂O₃ in human lung cancer cell line, H-460. The combination of GSD and AS₂O₃ synergistically augmented the cytotoxicity of GSD and AS₂O₃ in H-460 cells. The nature of cytotoxicity was revealed as apoptosis which was characterized by chromatin condensation and fragmentaton in DAPI staining. The apoptotic cytotoxicity of GSD and AS₂O₃ was accompanied by the cleavage of PARP. Of note, the expression of pro-apoptotic BclXS protein was increased, but the expressions of Sax and BclXL was not affected in H-460 cells treated with GSD and AS₂O₃. In addition, antioxidant NAC completely blocked the apoptotic death of H-460 cells by GSD and AS₂O₃. In conclusion, this results suggest that the cotreatment of GSD and AS203 induces the synergistic apoptotis of human large cell lung cancer cell line, H-460 via the induction of BclXS and reactive oxygen species (ROS).

• Korean Journal of Veterinary Service
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• v.35 no.3
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• pp.191-195
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• 2012

Accumulated evidence indicate that Ginkgo biloba extract (EGb 761) acts as an antioxidant and scavenger of free radicals as well as influencing apoptotis. Earlier studies have employed the inflammatory agent lipopolysaccharide (LPS) to induce severe sepsis. In the present study, we examined whether the intraperitoneal injection of EGb 761 increases the survival rate of mice in the LPS-induced severe sepsis model. The survival rate was significantly increased by 30% in mice administered with 100 mg/kg of EGb 761 but not in mice administered with 50 mg/kg EGb 761. In addition, pre-treatment with EGb 761 increased the survival rate (30%) but post-treatment with EGb 761 did not. These results suggest that EGb 761 may have clinical potential in preventing sepsis induced mortality.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1703-1706
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• 2013

Lung cancer remains a deadly disease with unsatisfactory overall survival. Resveratrol (Res) has the potential to inhibit growth of several types of cancer such as prostate and colorectal examples. In the current study, we evaluated in vitro and in vivo anticancer efficiency of Res in a xenograft model with A549 cells. Cell inhibition effects of Res were measured by MTT assay. Apoptotis of A549 cells was assessed with reference to caspase-3 activity and growth curves of tumor volume and bodyweight of the mice were measured every two days. In vitro cytotoxicity evaluation indicated Res to exert dose-dependent cell inhibition effects against A549 cells with activation of caspase-3. In vivo evaluation showed Res to effectively inhibit the growth of lung cancer in a dose-dependent manner in nude mice. Therefore, we believe that Res might be a promising phytomedicine for cancer therapy and further efforts are needed to explore this potential therapeutic strategy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.759-766
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• 2004

In the present study, we investigated the effects of aqueous extract of the healthful decoction utilizing Phellinus linteus (HDPL) on the cell growth of human lung carcinoma tumor cell line A549. Exposure of A549 cells to HDPL resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometric analysis. This increase in apoptosis was associated with inhibition and/or degradation of apoptotic target proteins such as poly(ADP-ribose) polymerase (PARP), b-catenin and phospholipase C- 1 (PLC- 1) protein. HDPL treatment induced the down-regulation of anti-apoptotic Bcl-2 expression, an anti-apoptotic gene, however, the level of Bax. a pro-apoptotic gene, was increased by HDPL treatment. In addition, HDPL-induced apoptotis of A549 cells was connected with activation of caspase-3 and caspase-9 protease in a dose-dependent manner, however, the levels of inhibitor of apoptosis proteins family were remained unchanged. Taken together, these results indicated that the anti-proliferative effects of HDPL were associated with the induction of apoptotic cell death through regulation of several major growth regulatory gene products such as Bcl-2 family expression and caspase protease activity, and HDPL may have therapeutic potential in human lung cancer.

• The Journal of Korean Medicine
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• v.23 no.4
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• pp.140-150
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• 2002

Objectives: The water extract of Omija-tang (OMIT) has traditionally been used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of OMJT rescues cells from these damages. Therefore, this study was designed to investigate the protective mechanisms of OMJT on oxidative stress-induced toxicity in H9c2 cardiomyoblast cells. Methods: Treatments of $H_2O_2$, or $ZnC_{12}$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. The characteristics of oxidative stress-induced death of H9c2 showed apparent apoptotic features such as DNA fragmentation. OMJT significantly reduced both ${H_2O_2}-induced$ cell death and chromatin fragmentation. The decrease of B치-XL expression by $H_2O_2$ were inhibited by OMJT. In addition, the increase of Bcl-XS expression was also inhibited by OMJT. In particular, Fas expression, which is generally recognized as cell death-inducing signal by Fas/FasL interaction, was markedly increased by H2O2 in a time-dependent manner. Also, the expression profile of proteins in Chang cells were screened by using two-dimensional (2-D) gel electrophoresis. Among 300 spots resolved in 2-D gels; the comparison of control versus apoptotis cells revealed that signal intensity of 6 spots decreased and 11 spots increased. Results and Conclusions: Taken together, this study suggests that the protective effects of the water extract of OMJT against oxidative damages may be mediated by the modulation of Bcl-XL/S Fas expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.1019-1030
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• 2003

Platycodi Radix, the root of Platycodon grandiflorum, commonly known as Doraji, is used as a traditional oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the growth of human lung carcinoma A549 cells. Results obtained are as fellow; AEPG treatment resulted in the inhibition of the cell viability of A549 cells in a concentration-dependent manner. Upon treatment with AEPG, A549 cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that AEPG increased populations of apoptotic-sub G1 phase. Western blot and RT-PCR analyses indicated that the expressions of Bcl-2 was down-regulated but Bax was up-regulated in AEPG-treated A549 cells. AEPG-induced apoptotis of A549 cells was associated with rroteolytic cleavage and activation of caspase-3, release of cytochrome c from mitochondria into cytosol and down-regulation of Akt and phospho-Akt proteins in a dose-dependent manner. Induction of apoptosis by AEPG treatment was associated with inhibition and/or degradation of apoptotic target proteins such as poly(ADP-ribose) polymerase, β-catenin and phospholipase C-γ 1. AEPG treatment inhibited the levels of cyclooxygenases protein of A549 cells, which was associated with the inhibition of prostaglandin E2 accumulation in a concentration-dependent fashion. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.402-409
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• 2016

It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.65-73
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• 2000

Objectives : The effects of cotreatment of adriamycin and ethanol extract of herb (Palgin-tang hab Hwajuck-hwan a traditional medicine for cancer treatment in oriental medicine) on the induction of apoptotic cell death were investigated in human liver origin cell lines, Chang. Methods : Chang(ATCC) liver cells were cultured in RPMI-1640(Gibco SRL Co, Gaithersburg, MD) badge including 10% fetal bovine serum. Chang liver cells were treated with various concentrations(from 10 to $0.16{\mu}l$) of adriamycin and herb extract(from 500 to $31.25{\mu}l$) After 48h later, the cells were tested for viability by Crystal violet staining assay. Adriamycin and Herb extract induced ladder pattern of DNA fragmentation in Chang cells. Genomic DNA was isolated and separated on 1.5% agarose gels. The DNA was stained with ethidium bromide and visualized under UV light. Results : The death of Chang cells was synergistically induced by the cotreatment of adriamycin and ethanol extract of herb. In addition, the cotreatment-induced cell death of Chang cells was mediated by apoptotic death signal processes. The phosphotransferase activity of JNK1 remained in a basal level in Chang cells which was treated individually with the adriamycin and ethanol extract of herb. However, it was markedly increased in Chang cells which was cotreated with adriamycin and ethanol extract of herb. In addition, the expression of Fas and FasL was markedly induced by the cotreatment of adriamycin and herb extract. For a while, the expression of Sax was a eminently increased by the ethanol extract of herb. However, Scl2 expression was not affected by the individual or cotreatment of adriamycin and herb extract. Conclusions : our results suggest that the cotreatment of adriamycin aM ethanol extract of herb induces synergistic apoptotis of human liver origin Chang cells via the upregulation of JNK, Fas, FasL and Bax.

• Journal of Life Science
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• v.19 no.11
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• pp.1529-1537
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• 2009

To elucidate further the antitumor effects of a natural L-arginine analogue, L-canavanine, the mechanism underlying apoptogenic activity of L-canavanine and its modulation by protein tyrosine kinase $p56^{lck}$ was investigated in human Jurkat T cells. When the cells were treated with 1.25 to 2.5 mM L-canavanine for 36 h, several apoptotic events including mitochondrial membrane potential (${\Delta\Psi}m$) loss, activation of caspase-9, -3, -8, and -7, poly (ADP-ribose) polymerase (PARP) degradation, and DNA fragmentation were induced without alteration in the levels of Fas or FasL. These apoptotic changes were more significant in $p56^{lck}$-deficient Jurkat clone JCaM1.6 than in $p56^{lck}$-positive Jurkat clone E6.1. The L-canavanine-induced apoptosis observed in $p56^{lck}$-deficient JCaM1.6 cells was significantly reduced by introducing $p56^{lck}$ gene into JCaM1.6 cells by stable transfection. Treatment of JCaM1.6/lck cells with L-canavanine caused a transient 1.6-fold increase in the kinase activity of $p56^{lck}$. Both FADD-positive wild-type Jurkat T cell clone A3 and FADD-deficient Jurkat T cell clone I2.1 exhibited a similar susceptibility to the cytotoxicity of L-canavanine, excluding involvement of Fas/FasL system in triggering L-canavanine-induced apoptosis. The L-canavanine-induced apoptotic sub-$G_1$ peak and activation of caspase-3, -8, and -7 were abrogated by pan-caspase inhibitor (z-VAD-fmk), whereas L-canavanine-induced activation of caspase-9 was not affected. These results demonstrated that L-canavanine caused apoptosis of Jurkat T cells via the loss of ${\Delta\Psi}m$, and the activation of caspase-9, -3, -8, and -7, leading to PARP degradation, and that the $p56^{lck}$ kinase attenuated the ${\Delta\Psi}m$ loss and activation of caspases, and thus contributed as a negative regulator to L-canavanine-induced apoptosis.