• 한방안이비인후피부과학회지
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• 제24권1호
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• pp.16-24
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• 2011

Objective : In this study, we investigated the effects of ethanol extract of Anemarrhenae Rhizoma (EAR) on the proliferation and apoptosis induction of HT-29 human colon cancer cells. Methods : Cell viability of HT-29 cells were measured by MTT assay and apoptisis-related proteins were assessed using western blotting. Chromatin condensation of HT-29 cells stained with Hoechst 33258. Results : In the present study, we demonstrated that EAR exhibited significant cytotoxicity in HT-29 cells. The induction of apoptosis in HT-29 cells by EAR treatment was characterized by chromatin condensation and the activation of caspase-3. EAR-induced apoptosis is accompanied by the release of cytochrome c and the specific proteolytic cleavage of PARP. EAR was appeared cytotoxic effect to HT-29 cells in a dose-dependent manner. Concomitantly, EAR treatment led to increase in the caspase-9. The reduction of Bcl-2 and truncation of Bid were induced by EAR. Conclusion : We studied that the EAR induced apoptosis in human colon adenocarcinoma HT-29 cells. These results indicated that EAR can cause apoptosis through mitochondria/caspase pathway in human HT-29 cells.

• 대한의생명과학회지
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• 제12권3호
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• pp.161-170
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• 2006

A new piperazine derivative, 8J-8029, is a synthetic anti-cancer agent which exhibits both microtubule and topoisomerase II inhibiting activities. In this study, we investigated the ability of 8J-8029 for anti-angiogenesis and apoptosis. 8J-8029 decreased the bFGF-induced angiogenesis in the CAM and the mouse Matrigel implants, in vivo. 8J-8029 inhibited the proliferation, migration, invasion, tube fonnation, and expression of MMP-2 in BAECs. In addition, 8J-8029 reduced the cell viability in HepG2 cells, caused the production of fragmented DNA and the morphological changes corresponding to apoptosis. 8J-8029 also elicited the release of cytochrome c and the activation of caspase-3. Taken together, these results suggest 8J-8029 may be a candidate for anti-cancer agent with the ability to inhibit the angiogenesis of endothelial cells and to induce the apoptosis of tumor cells.

• Biomolecules & Therapeutics
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• 제24권2호
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• pp.147-155
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• 2016

Chaetominine is a quinazoline alkaloid originating from the endophytic fungus Aspergillus fumigatus CY018. In this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia K562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. Chaetominine inhibited K562 cell growth, with an $IC_{50}$ value of 35 nM, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. The high apoptosis rates, morphological apoptotic features, and DNA fragmentation caused by chaetominine indicated that the cytotoxicity was partially caused by its pro-apoptotic effect. Under chaetominine treatment, the Bax/Bcl-2 ratio was upregulated (from 0.3 to 8), which was followed by a decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria into the cytosol, and stimulation of Apaf-1. Furthermore, activation of caspase-9 and caspase-3, which are the main executers of the apoptotic process, was observed. These results demonstrated that chaetominine induced cell apoptosis via the mitochondrial pathway. Chaetominine inhibited K562 cell growth and induced apoptotic cell death through the intrinsic pathway, which suggests that chaetominine might be a promising therapeutic for leukemia.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6369-6374
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• 2012

Vitexicarpin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), a polymethoxyflavone isolated from Viticis Fructus (Vitex rotundifolia Linne fil.), has long been used as an anti-inflammatory herb in traditional Chinese medicine. It has also been reported that vitexicarpin can inhibit the growth of various cancer cells. However, there is no report elucidating its effect on human prostate carcinoma cells. The aim of the present study was to examine the apoptotic induction activity of vitexicarpin on PC-3 cells and molecular mechanisms involved. MTT studies showed that vitexicarpin dose-dependently inhibited growth of PC-3 cells with an $IC_{50}{\sim}28.8{\mu}M$. Hoechst 33258 staining further revealed that vitexicarpin induced apoptotic cell death. The effect of vitexicarpin on PC-3 cells apoptosis was tested using prodium iodide (PI)/Annexin V-FITC double staining and flow cytometry. The results indicated that vitexicarpin induction of apoptotic cell death in PC-3 cells was accompanied by cell cycle arrest in the G2/M phase. Furthermore, our study demonstrated that vitexicarpin induction of PC-3 cell apoptosis was associated with upregulation of the proapoptotic protein Bax, and downregulation of antiapoptotic protein Bcl-2, release of Cytochrome c from mitochondria and decrease in mitochondrial membrane potential. Our findings suggested that vitexicarpin may become a potential leading drug in the therapy of prostate carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.2993-2999
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• 2014

Saccharina japonica is a family member of Phaeophyceae (brown macro-alga) and extensively cultivated in China, Japan and Korea. Here, the potential anti-cancer effect of n-hexane fraction of S. japonica was evaluated in SK-Hep1 human hepatocellular carcinoma cells. The N-hexane fraction reduced cell viability and increased the numbers of apoptotic cells in a both dose- and time-dependent manner. Apoptosis was activated by both caspase-dependent and independent pathways. The caspase-dependent cell death pathway is mediated by cell surface death receptors and activated caspase-8 amplified the apoptotic signal either through direct activation of downstream caspase-3 or pro-apoptotic proteins (Bad, Bax and Bak) subsequently leading to the release of cytochrome c. On the other hand, caspase-independent apoptosis appeared mediated by disruption of mitochondrial membrane potential and translocation of AIF to the nucleus where they induced chromatin condensation and/or large-scale DNA fragmentation. In addition, the n-hexane fraction induced endoplasmic reticulum (ER)-stress and cell cycle arrest. The results suggested that potential anti-cancer effects of n-hexane extract from S. japonica on SK-Hep1 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5201-5205
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• 2014

Emodin, a natural anthraquinone isolated from the traditional Chinese medicine Radix rhizoma Rhei, can induce apoptosis in many kinds of cancer cells. This study demonstrated that emodin induces apoptosis in human colon cancer HCT116 cells by provoking oxidative stress, which subsequently triggers a p53-mitochondrial apoptotic pathway. Emodin induced mitochondrial transmembrane potential loss, increase in Bax and decrease in Bcl-2 expression and mitochondrial translocation and release of cytochrome c to cytosol in HCT116 cells. In response to emodin-treatment, ROS increased rapidly, and subsequently p53 was overexpressed. Pretreatment with the antioxidant NAC diminished apoptosis and p53 overexpression induced by emodin. Transfecting p53 siRNA also attenuated apoptosis induced by emodin, Bax expression and mitochondrial translocation being reduced compared to treatment with emodin alone. Taken together, these results indicate that ROS is a trigger of emodin-induced apoptosis in HCT116 cells, and p53 expression increases under oxidative stress, leading to Bax-mediated mitochondrial apoptosis.

• 한국수산과학회지
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• 제45권6호
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• pp.553-560
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• 2012

Hizikia fusiformis, a brown alga that is widely consumed in Korea, Japan, and China, possesses a number of potentially beneficial compounds, including antioxidants and anticoagulants. However, the molecular mechanisms of H. fusiformis in hepatoma cells have not been elucidated. This study investigated the antiproliferative effect and mechanism of action of a glycoprotein from H. fusiformis (HFGP) in HepG2 human hepatoma cells. In an MTS assay, 25 ${\mu}g/mL$ HFGP inhibited the proliferation of HepG2 cells by $52.36{\pm}2.37%$. HFGP caused the dose-dependent growth inhibition of HepG2 cells by inducing apoptosis and a sub-G1 phase arrest. The antiproliferative activity of HFGP was confirmed based on the expression of several apoptosis-related proteins, which was assessed by Western blot analysis. The expressions of Fas, Fas-associated death domain protein, Bax, and Bad was significantly up-regulated in HFGP-treated cells, and HFGP induced the translocation of Bax to mitochondria and the release of cytochrome c into the cytosol. Therefore, HFGP might be useful in the treatment of liver cancer.

• 동의생리병리학회지
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• 제22권2호
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• pp.438-445
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• 2008

Dodam formula (Dodam) has been used for neurodegenerative disease in Oriental medicine. Dodam is capable of protecting diverse kinds of cells from damage caused by a variety of toxic stimuli. In the present study, we investigated the underlying protective mechanism of Dodam on rotenone-induced cytotoxicity in rat neuroblastoma Neuro-2A cells. Treatment with Neuro-2A cells with rotenone caused the loss of cell viability, and condensation and fragmentation of nuclei, which was associated with the elevation of ROS level, and lipid peroxidation, the increase in Bax/Bcl-2 ratio. Rotenone induced mitochondrial dysfunction characterized by mitochondrial membrane potential loss and cytochrome-c release. These phenotypes induced by rotenone were reversed by pretreatment with Dodam. Our results suggested that major features of rotenone-induced neurotoxicity are partially mediated by mitochondrial dysfunction and oxidative stress, and that Dodam markedly protects Neuro-2A cells from oxidative injury. These data indicated that Dodam might provide a useful therapeutic strategy in treatment of the neurodegenerative diseases caused by oxidative injuries.

• 대한한방부인과학회지
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• 제19권1호
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• pp.97-110
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• 2006

Purpose : To address the ability of Myrrha (MY) to induce cell death, we investigated the effect of MY on apoptosis. In human cervical carcinoma HeLa cells, apoptosis occurred following MY exposure in a dose-dependent manner. Methods : We have tested several kinds of anti-oxidants to investigate the MY-induced apoptotic mechanism. Among the anti-oxidants, N-acetyl cysteine(NAC) or reduced glutathione (GSH) protects MY-induced apoptosis. NAC is an aminothiol and synthetic precursor of intracellular cysteine and GSH. To confirm the role of GSH in MY-induced apoptosis, methionine and cystathionine-glutathione extrusion inhibitors were treated in the presence of MY. Results : NAC, GSH, methionine or cystathionine led to protective effect against MY-induced apoptosis in HeLa cells. The GSH and GSH-associated reagents regulate MY-induced cytochrome c release and the resultant caspase-3 activation. Furthermore, the two specific inhibitors of carrier-mediated GSH extrusion, methionine and cystathionine demonstrate GSH extrusion occurs via a specific mechanism. While decreasing GSH extrusion and protecting against MY-induced apoptosis, methionine and cystathionine failed to exert anti-apoptotic activity in cells previously deprived of GSH. Conclusion : the target of the protection is indeed GSH extrusion. This shows that the protective effect is achieved by forcing GSH to stay within the cells during apoptogenic treatment. All this evidence indicates the extrusion of GSH precedes andis responsible for the apoptosis, probably by altering the intracellular redox state, thus giving a rationale for the development of redox-dependent apoptosis in MY-treated human cervical carcinoma HeLa cells.

• 한국환경성돌연변이발암원학회지
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• 제20권1호
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• pp.14-20
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• 2000

DHAQ-97, (2-(3-[p-bis(2-chloroethyl)aminophenyl]-2 formylaminopropanoyloxy) methy1-1,4-dihy-droxy-9,10-anthraquinone), is a novel anthraquinone derivative synthesized for use as an anti-neoplastic agent. In the present study, we have evaluated the selective cytotoxicity of DHAQ-97 by comparing its effects on viability and proliferation of human breast cancer cell line (NCF-7) versus normal immortalized breast epithelial cell line (MCF-10A). Thus, DHAQ-97 reduced both viability and proliferation of MCF-7 cells to a much greater extent than did for MCF-10A cells. The growth inhibitory and anti-proliferative properties of DHAQ-97 appear to be attributable to its ability to induce apoptosis as revealed by positive staining after in 냐셔 nick-end labeling (TUNEL), cleavage of poly(ADP-ribose)polymerase, release of mitochondrial cytochrome c into cytoplasm, and increased expression of pro-apoptotic Bax protein. Recent studies have indicated possible involvement of the ubiquitous eukaryotic transcription factor, NF-kappa B (NF-kB) in the regulation of apoptotic cell death. In line induced cytotoxicity in cultured MCF-7 cells. Furthermore, mild activation of NF-kB, as determined by its increased DNA binding capability, was observed 30 min after treatment with 10$\mu\textrm{m}$ DHAQ-97. Taken together, the above findings suggest that DHAQ-97 exerts selective cytotoxicity towards cancer cells through induction of apoptosis, which appears to be regulated by NF-kB.