• Proceedings of the PSK Conference
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• 2003.10b
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• pp.117.3-118
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. (omitted)

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.225-232
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• 2015

We identified a novel Akt signaling mechanism that mediates fucoidan-induced suppression of human colon cancer cell (HT29) proliferation and anticancer effects. Fucoidan treatment significantly inhibited growth, induced G1-phase-associated upregulation of p21WAF1 expression, and suppressed cyclin and cyclin-dependent kinase expression in HT29 colon cancer cells. Additionally, fucoidan treatment activated the Akt signaling pathway, which was inhibited by treatment with an Akt inhibitor. The inhibition of Akt activation reversed the fucoidan-induced decrease in cell proliferation, the induction of G1-phase-associated p21WAF1 expression, and the reduction in cell cycle regulatory protein expression. Intraperitoneal injection of fucoidan reduced tumor volume; this enhanced antitumor efficacy was associated with induction of apoptosis and decreased angiogenesis. These data suggest that the activation of Akt signaling is involved in the growth inhibition of colon cancer cells treated with fucoidan. Thus, fucoidan may serve as a potential therapeutic agent for colon cancer.

• Journal of Microbiology and Biotechnology
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• v.32 no.6
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• pp.718-729
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• 2022

Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy with poor prognosis. Here, due to the necessity for exploring potential therapies against ESCC, we obtained the gene expression data on ESCC from the TCGA and GEO databases. Venn diagram analysis was applied to identify common targets. The protein-protein interaction network was constructed by Cytoscape software, and the hub targets were extracted from the network via cytoHubba. The potential hub nodes as drug targets were found by pharmacophore-based virtual screening and molecular modeling, and the antitumor activity was evaluated through in vitro studies. A total of 364 differentially expressed genes (DEGs) in ESCC were identified. Pathway enrichment analyses suggested that most DEGs were mainly involved in the cell cycle. Three hub targets were retrieved, including CENPF, CCNA2 (cyclin A), and CCNB1 (cyclin B1), which were highly expressed in esophageal cancer and associated with prognosis. Moreover, amentoflavone, a promising drug candidate found by pharmacophore-based virtual screening, showed antiproliferative and proapoptotic effects and induced G1 in esophageal squamous carcinoma cells. Taken together, our findings suggested that amentoflavone could be a potential cell cycle inhibitor targeting cyclin B1, and is therefore expected to serve as a great therapeutic agent for treating esophageal squamous cell carcinoma.

• Journal of Life Science
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• v.24 no.1
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• pp.92-97
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• 2014

Cordycepin, an active component originally isolated from the traditional medicine Cordyceps militaris, is a derivative of the nucleoside adenosine, which has been shown to possess a number of pharmacological properties, including antioxidant and anti-inflammatory activities, immunological stimulation, and antitumor effects. This study was conducted on cultured human prostate carcinoma LNCap cells to elucidate the possible mechanisms by which cordycepin exerts its anticancer activity, which, until now, has remained poorly understood. Cordycepin treatment of LNCap cells resulted in dose-dependent inhibition of cell growth and the induction of apoptotic cell death as detected by an MTT assay, cleavage of poly ADP-ribose polymerase, and annexin V-FITC staining. Flow cytometric analysis revealed that cordycepin resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and cyclin A expression in a concentration-dependent manner. Moreover, the incubation of cells with cordycepin caused a striking induction in the expression of the cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1 without affecting the expression of the tumor suppressor p53. It also resulted in a significant increase in the binding of CDK2 and CDC2 to p21. These findings suggest that cordycepin-induced G2/M arrest and apoptosis in human prostate carcinoma cells is mediated through p53-independent upregulation of the CDK inhibitor p21.

• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.1-8
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• 2008

Mitochondria are important sensor of apoptosis. $H_2O_2-induced$ cell death rate was enhanced by serum deprivation. In this study, we investigated whether serum deprivation using 0.5 or 3 % FBS induces apoptotic cell death through mitochondrial enzyme activation as compared to 10 % FBS. Apoptotic cell death was observed by chromosome condensation and the increase of sub-G0/G1 population. Serum deprivation reduced cell growth rate, which was confirmed by the decrease of S-phase population in cell cycle. Serum deprivation significantly increased caspase-9 activity and cytochrome c release from mitochondria into cytosol. Serum deprivation-induced mitochondrial changes were also indicated by the increase of ROS production and the activation of mitochondrial enzyme, succinate dehydrogenase. Mitochondrial enzyme activity increased by serum deprivation was reduced by the treatment with rotenone, mitochondrial electron transport inhibitor. In conclusion, serum deprivation induced mitochondrial apoptotic cell death through the elevation of mitochondrial changes such as ROS production, cytochrome c release and caspase-9 activation. It suggests that drug sensitivity could be enhanced by the increase of mitochondrial enzyme activity in serum-deprived condition.

• The Journal of Internal Korean Medicine
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• v.36 no.1
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• pp.13-21
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• 2015

Objectives : In Korea, Rhus verniciflua Stokes (RVS) has been used in traditional medicine for various diseases such as back pain, syndromes of the blood system in women, gastrointestinal disease, and cancer. However, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated yet. Methods : This study investigated the possible mechanisms by which RVS extract (RVE) exerts its anti-proliferative action in cultured human breast carcinoma MCF-7 cells. Results : Treatment with RVE in MCF-7 cells resulted in inhibition of cell viability through G1 arrest of the cell cycle and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by RVE treatment was associated with the inhibition of cyclin D1, cyclin-dependent kinase (Cdk) 2, retinoblastoma protein (pRB), and mouse double minute 2 (MDM2) expression. Moreover, RVE treatment concentration dependently increased the levels of tumor suppressor p53, which was associated with the marked induction of Cdk inhibitors such as p21 (Waf1/Cip1) and p27 (Kip1). However, the inhibition of p53 function by the wild-type p53-specific inhibitor, pifithrin-α, abolished the above-mentioned effects of RVE, showing that p53 was responsible for the cytotoxicity of RVE Conclusions : These data indicate that a molecular pathway involving p53-dependent G1 cell cycle arrest plays a pivotal role in the cellular response to RVE, and demonstrate the potential applications of RVE as an anti-cancer drug for breast cancer treatment.

• Journal of Microbiology and Biotechnology
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• v.19 no.11
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• pp.1482-1489
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• 2009

In this study, we investigated the anti-proliferative effect of polysaccharides from Salicornia herbacea on HT-29 human colon cancer cells. Crude polysaccharides from S. herbacea (CS) were prepared by extraction with hot steam water, and fine polysaccharides from S. herbacea (PS) were obtained through further size exclusion chromatography. The anti-proliferative effect of CS and PS were measured using the MTS assay, apoptosis analysis, cell cycle analysis, and RT-PCR. HT-29 cells were treated with CS or PS at different dosages (0.5, 1, 2, 4 mg $ml^{-1}$) for 24 or 48 h. CS and PS inhibited proliferation and stimulated apoptosis of cells in a dose-dependent manner. Flow cytometric analysis after Annexin V-FITC and PI staining revealed that treatment with CS or PS increased total apoptotic death of cells to 24.99% or 91.59%, respectively, in comparison with the control (13.51 %). PS increased early apoptotic death substantially - up to 12 times more than the control. Treatment with CS or PS resulted in a concentration-dependent increase of the G2/M cell population of the cell cycle as determined by flow cytometry. G2/M arrest was induced significantly with the highest concentration (4 mg $ml^{-1}$) of PS. RT-PCR was performed to study the correlation between G2/M arrest and transcription of cell cycle control genes. The anti-proliferative activity of CS and PS was accompanied by inhibition of cyclin B1, and Cdc 2 mRNA. Moreover, both CS and PS induced expression of the p53 tumor suppressor gene and the Cdk inhibitor p21. These results suggest that polysaccharides from S. herbacea have anti-cancer activity in human colon cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2453-2458
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• 2015

Background: X-linked inhibitor of apoptosis protein (XIAP) associated factor 1 (XAF1) exhibits aberrantly low or absent expression in various human malignancies, closely associated with anti-apoptosis and overgrowth of cancer cells. However, limited attention has been directed towards the contribution of XAF1 to invasion, apoptosis, and cisplatin (DDP)-resistance of epithelial ovarian cancer (EOC) cells. This study aimed to evaluate the potential effects of XAF1 on invasion, cell cycle, apoptosis, and cisplatin-resistance by overexpressing XAF1 in SKOV-3 and SKOV-3/DDP cells. Methods and Results: The pEGFP-C1-XAF1 plasmid was transfected into SKOV-3 and SKOV-3/DDP cells, and the expression of XAF1 at both mRNA and protein levels was analyzed by reverse transcription-PCR and Western blotting. Overexpression of XAF1 suppressed XIAP expression in both SKOV-3 and SKOV-3/DDP cells. Transwell invasion assays demonstrated that XAF1 exerted a strong anti-invasive effect in XAF1-overexpressing cells. Moreover, flow cytometry analysis revealed that XAF1 overexpression arrested the cell cycle at G0/G1 phase, and cell apoptosis analysis showed that overexpression of XAF1 enhanced apoptosis of SKOV-3 and SKOV-3/DDP cells apparently by activating caspase-9 and caspase-3. Furthermore, MTT assay confirmed a dose-dependent inhibitory effect of cisplatin in the tested tumor cells, and overexpression of XAF1 increased the sensitivity of SKOV-3 and SKOV-3/DDP cells to cisplatin-mediated antiproliferative effects. Conclusions: In summary, our data indicated that overexpression of XAF1 could suppress XIAP expression, inhibit invasion, arrest cell cycle, promote apoptosis, and confer cisplatin-sensitivity in SKOV-3 and SKOV-3/DDP cells. Therefore, XAF1 may be further assessed as a potential target for the treatment of both cisplatin-resistant and non-resistant EOCs.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1235-1242
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• 2006

Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human canter cells, however its molecular mechanisms are poorly understood. In tile present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human hepatocarcinoma HepG2 cells. Treatment of HepG2 cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by DNA flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells suggesting that sulforaphane induced apoptosis. This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of ryclin A, cyclin 31 and Cdc2 protein. However, the levels of tumor suppressor p53 and Cdk inhibitor p21 mRNA and protein expression were significantly increased by sulforaphane treatment in a concentration-dependent manner. Although further studies are needed, the present work suggests that sulforaphane may be a potential rhemoprevetiveichemotherapeucc agent for the treatment of human cancer cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.183-189
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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. We investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the cell proliferation of human lung carcinoma A549 cells in order to understand its anti-proliferative mechanism. AEPG treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner. This anti-proliferative effect of A549 cells by AEPG treatment was associated with morphological changes such as membrane shrinking, cell rounding up and inhibition of cell migration. DNA flow cytometric histograms showed that populations of both Sand G2/M phase of the cell cycle were increased by AEPG treatment in a concentration-dependent manner. AEPG treatment induced a marked accumulation of tumor suppressor p53 and a concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21 and p27. In addition, SSS treatment resulted in down-regulation of Cdk2 and Cdk4 expression. The present results indicated that AEPG-induced inhibition of lung cancer cell proliferation is associated with the blockage of S to G2/M phase progression the induction of apoptosis. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.