• Biomolecules & Therapeutics
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• 제32권1호
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• pp.123-135
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• 2024

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G₀/G₁ phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

• Journal of Yeungnam Medical Science
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• 제32권1호
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• pp.1-7
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• 2015

Over several decades, a hierarchical cancer stem cell (CSC) model has been established in development of solid cancers, including hepatocellular carcinoma(HCC). In terms of this concept, HCCs originate from liver CSCs. Clinically HCCs show a wide range of manifestations from slow growth to very aggressive metastasis. One of the reasons may be that liver CSCs originate from different cells. This review describes the basic concept of CSCs and the cellular origin of liver CSCs.

• International Journal of Contents
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• 제8권4호
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• pp.74-77
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• 2012

Radiation has been an effective tool for treating cancer for a long time. Radiation therapy induces DNA damage within cancer cells and destroys their ability to reproduce. Radiation therapy is often combined with other treatments, like surgery and chemotherapy. Here, we describe the effects of radiation and histone deacetylase inhibitor, Trichostain A, on cell cycle regulation in hepatoma cells. The combinatorial treatment of radiation and Trichostain A induced cell cycle arrest and thereby increasing the hepatoma cell death. Furthermore, the regulatory effects of radiation and Trichostatin A on cell cycle applied in cell type specifically. These results suggest that the treatment of radiation and Trichostatin A may play a central role in hepatoma cell death and might be a good remedy to improve the efficiency of radiation therapy.

• Molecules and Cells
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• 제38권5호
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• pp.457-465
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• 2015

The 15-kDa selenoprotein (Sep15) is a selenoprotein residing in the lumen of the endoplasmic reticulum (ER) and implicated in quality control of protein folding. Herein, we established an inducible RNAi cell line that targets Sep15 mRNA in Chang liver cells. RNAi-induced Sep15 deficiency led to inhibition of cell proliferation, whereas cell growth was resumed after removal of the knockdown inducer. Sep15-deficient cells were arrested at the G1 phase by upregulating p21 and p27, and these cells were also characterized by ER stress. In addition, Sep15 deficiency led to the relocation of focal adhesions to the periphery of the cell basement and to the decrease of the migratory and invasive ability. All these changes were reversible depending on Sep15 status. Rescuing the knockdown state by expressing a silent mutant Sep15 mRNA that is resistant to siRNA also reversed the phenotypic changes. Our results suggest that SEP15 plays important roles in the regulation of the G1 phase during the cell cycle as well as in cell motility in Chang liver cells, and that this selenoprotein offers a novel functional link between the cell cycle and cell motility.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.331-341
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• 2021

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

• 대한기계학회:학술대회논문집
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• 대한기계학회 2008년도 추계학술대회A
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• pp.1539-1542
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• 2008

Plasma is 4th state of matters, which consists of electrons, neutral, and ionized particles. In biomedical research, cold plasma, which is generated in atmospheric condition, has been applied to disinfect microorganisms such as bacteria and yeast cells. Because of its low temperature condition, the heat-sensitive medical device can be easily sterilized by the cold plasma treatment. In recent years, the effects of plasma on mammalian cells have arisen as a new issue. Generally, plasma induces intensity dependent necrotic cell death. In this research, we investigate the feasibility of cold plasma treatment for cancer therapy by conducting comparative study of plasma effects on normal and cancer cells. We use THLE-2 (human liver normal cell) and SK-Hep1 (human liver metathetic cancer cell) as our target cells. The needle type of cold plasma is generated by the Helium plasma device. Two types of cells have different onset plasma conditions for the necrosis, which may be explained by difference in electrical properties of these two cell types.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1349-1353
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• 2012

Increasing evidence has revealed that thy-1 was a potential stem cell marker of liver cancer, but no data have been shown on how thy-1 regulates the pathophysiology of liver cancer, such as proliferation, apoptosis, invasion and migration. We previously demonstrated that thy-1 was expressed in about 1% of hepg2 cells, thy-1+hepg2 cells, but not thy-1-, demonstrating high tumorigenesis on inoculation $0.5{\times}10^5$ cells per BACA/LA mouse after 2 months. In the present study, our results showed that higher expression of thy-1 occurs in 72% (36/50 cases) of neoplastic hepatic tissues as compared to 40% (20/50 cases) of control tissues, and the expression of thy-1 is higher in poorly differentiated liver tumors than in the well-differentiated ones. In addition, thy-1 expression was detected in 85% of blood samples from liver cancer patients, but none in normal subjects or patients with cirrhosis or hepatitis. There was a significant negative correlation between thy-1expression and E-cadherin expression (a marker of invasion and migraton), but not between thy-1 expression and AFP expression in all the liver cancer and blood samples. We further investigated the relationship between thy-1 and E-cadherin in liver cancer hepg2 cell line which was transfected with pReceiver-M29/thy-1 eukaryotic expression vector followed by aspirin treatment. Lower expression of E-cadherin but higher expressions of thy-1 were detected in hepg2 cells transfected with pReceiver-M29/thy-1. Taken together, our study suggested that thy-1 probably regulates liver cancer invasion and migration.

• 대한한방내과학회지
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• 제26권2호
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• pp.320-332
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• 2005

Objectives: The aim of the experiment is to identify any anti-tumor effects of Duchesnea indica(Andr.) Focke on stomach, liver, urinary bladder, prostate and kidney cancer cells. Materials & Methods: For cancer cells, AGS stomach, Hep3B and Hep3G2 liver, HT-1197, HT-1376 urinary bladder, PC3 prostate, and A-704 kidney cancer cells, all obtained from Korean Ce 11 Line Bank, were used. The boiled extract of Duchesnea indica(Andr.) Focke (10 and 20 microliters) was injected into cultures, and the cultures were observed at 0, 6 and 12 hours, and from then on at 12 hours intervals up to 72 hours. The destruction of stomach, liver, urinary bladder, prostate and kidney cancer cells were measured through Trypan blue exclusion testing. The suppresion on viability of stomach, liver, urinary bladder, prostate and kidney cancer cells was measured via MTT assay. Anti-cancer mechanisms were assessed by analyzing the cell cycle. Results: In morphologic change, AGS, Hep3B, HepG2 showed the withdrawn and floating appearance that is typical in cellular impairment. The destruction of AGS, HT-1197, HT-1376, A-704, PC-3, Hep3B and HepG2 cancer cells in each test group was greater than that in the control group to a statistically significant degree. The suppression on viability of AGS, HT-1197 and Hep3G in each test group was greater than that in the control group to a statistically significant degree. Analysis of the cell cycle after injection of D... Focke showed inhibition of cell division in all test groups(AGS, Hep3B, HepG2, HT-1197, HT-1376, PC3, A-704). Conclusions: The results of this experiment suggest that Duchesnea indica(Andr.) Focke has statistically significant anti-tumor effects on stomach, urinary bladder, kidney, prostate and liver cancer, of which stomach and liver cancer are prominently significant. This in vitro experiment supports a role for Duchesnea indica(Andr.) Focke as a potential cancer treatment, but progressive research on Duchesnea indica(Andr.) Focke and its anti-tumor effects is needed to develop a practical application for it in cancer treatment.

• 동의생리병리학회지
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• 제26권4호
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• pp.519-526
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• 2012

Recently, herbal flavonoids have been implicated for anti-cancer therapy. Flavonoids as a commonly known for their anti-oxidant activity, are contained in the herbal medicine as well as root of plants, vegetables, fruits, grains, tea, and wine. Kaempferol, a component of Polygonati rhizoma, a member of the herbal flavonoids, has been studied for anti-hypercholesterol, anti-hypertension and anti-diabetes. It is also known to be effective in anti-cancer therapy for breast, prostate and other type of cancers. However, the anti-cancer therapeutic mechanisms are pooly understood. Here, we investigated the molecular mechanism underlying kaempferol-induced anti-cancer effects using the human liver cancer cell lines, Hep3B, HepG2, and Sk-Hep-1, and human Chang liver cell as a control. As shown by the FACS analysis, measurement of caspase activity, DAPI and trypan blue staining, and DNA fragmentation assay, kaempferol induced apoptosis in the liver cancer cells with the greater potential in Hep3B cells than other liver cancer cells. In addition, we performed microarray analysis to profile the genome-wide mRNA expression regulated by kaempferol. Many of the apoptosis-related genes were significantly induced in kaempferol-treated Hep3B cells, in particular, the genes associated with MAPK cascade. Additionally, kaempferol induced the mRNA expression of genes involved in MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathway, which are all known to trigger apoptosis. Overall, our data suggest that kaempferol has anti-liver cancer effects by inducing apoptosis through the MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathways.

• Genomics & Informatics
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• 제21권4호
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• pp.48.1-48.8
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• 2023

Liver cancer is the fourth leading cause of death worldwide. Well-known risk factors include hepatitis B virus and hepatitis C virus, along with exposure to aflatoxins, excessive alcohol consumption, obesity, and type 2 diabetes. Genomic variants play a crucial role in mediating the associations between these risk factors and liver cancer. However, the specific variants involved in this process remain under-explored. This study utilized a bioinformatics approach to identify genetic variants associated with liver cancer from various continents. Single-nucleotide polymorphisms associated with liver cancer were retrieved from the genome-wide association studies catalog. Prioritization was then performed using functional annotation with HaploReg v4.1 and the Ensembl database. The prevalence and allele frequencies of each variant were evaluated using Pearson correlation coefficients. Two variants, rs2294915 and rs2896019, encoded by the PNPLA3 gene, were found to be highly expressed in the liver tissue, as well as in the skin, cell-cultured fibroblasts, and adipose-subcutaneous tissue, all of which contribute to the risk of liver cancer. We further found that these two SNPs (rs2294915 and rs2896019) were positively correlated with the prevalence rate. Positive associations with the prevalence rate were more frequent in East Asian and African populations. We highlight the utility of this population-specific PNPLA3 genetic variant for genetic association studies and for the early prognosis and treatment of liver cancer. This study highlights the potential of integrating genomic databases with bioinformatic analysis to identify genetic variations involved in the pathogenesis of liver cancer. The genetic variants investigated in this study are likely to predispose to liver cancer and could affect its progression and aggressiveness. We recommend future research prioritizing the validation of these variations in clinical settings.