• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.993-1001
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• 2016

Type 2 diabetes mellitus patients are at increased risk of many forms of malignancies, especially of the pancreas, colon and hepatocellular cancer. Unfortunately, little is known of the possible interaction between antidiabetic drugs and anticancer agents. The present study investigates the influence of metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular liver carcinoma cell line (HepG2) viability and apoptosis were determined by the MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D, respectively, after treatment with EpoA, metformin or sitagliptin. The levels of nuclear factor NF-${\kappa}B$ and p53 were evaluated in the presence and absence of inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not. EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the level of NF-${\kappa}B$. Only MET enhanced the proapoptotic effect of EpoA. The EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led to apoptosis independent of p53, decreasing the level of NF-${\kappa}B$. These findings support the link between NF-${\kappa}B$ and p53 in the modulation of apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic effect on liver cancer cells than each of the compounds alone. The therapeutic advantages of the combination of EpoA with MET may be valuable in the treatment of patients with diabetes mellitus type 2 (T2DM) and liver cancer.

• Journal of Life Science
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• v.21 no.11
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• pp.1549-1557
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• 2011

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in many types of transformed cells; however, some human hepatocellular carcinoma cells are particularly resistant to the effects of TRAIL. Although genistein, a natural isoflavonoid phytoestrogen, has been shown to have pro-apoptotic activity against human cancer cell lines, little is known about the mechanism of genistein in terms of TRAIL-induced apoptosis. In the present study, it was investigated whether or not combined treatment with genistein and TRAIL synergistically induced apoptosis in Hep3B hepatocarcinoma cells. Results indicate that treatment with TRAIL in combination with nontoxic concentrations of genistein sensitized TRAIL-resistant Hep3B cells to TRAIL-induced apoptosis, which was associated with mitochondrial dysfunction. Further, the inhibition of p38 mitogen-activated protein kinase (MAPK) activation markedly decreased genistein and TRAIL-induced cell viability and apoptosis by enhanced truncation of Bid, increase of pro-apoptotic Bax, decrease of anti-apoptotic Bcl-2, and release of cytochrome c from mitochondria to cytoplasm. Activation of caspases and degradation of poly (ADP-ribose) polymerase induced by the combined treatment was also markedly increased by the inhibition of p38 MAPK, through the mitochondrial amplification step. In conclusion, our data suggest that genistein sensitizes TRAIL-induced-apoptosis via p38 MAPK-dependent pathway.

• Journal of Microbiology and Biotechnology
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• v.9 no.4
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• pp.504-508
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• 1999

This report compares the selective cytotoxic effects of Doenjang fermented by various Bacillus strains (Bacillus sp. SS9, SSA3, and PM3) on human liver cell lines with that of conventional Doenjang (DTY, DTG, and DTK) and commercial Doenjang (DCM, DCD, and DCS). To investigate selective cytotoxic effects of Doenjang extracts, the cell density of HepG2 (Hepatocellular carcinoma) and CCL-13 (cells derived from human normal liver) was estimated after addition of the extracts by using a viable cell counting method. The maximum selectivity ratio ($IC_{50}$value against CCL-13/$IC_{50}$ value aganist HepG2) was observed by PM3 (extracts of Doenjang fermented with Bacillus sp. PM3). As for morphological changes shown by the addition of PM3 into HepG2 and CCL-13 cultures, HepG2 was significantly disrupted, however, CCL-13 was not affected. Also, the growth rate of HepG2 was decreased significantly by the addition of PM3. Consequently, PM3 showed a more detrimental effect on HepG2 than that on CCL-13.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1719-1722
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• 2012

The Wiskott-Aldrich Syndrome Protein family Verprolin - homologous proteins (WAVEs), encoded by a metastasis promoter gene, play considerable roles in adhesion of immune cells, cell proliferation, migration and destruction of foreign agents by reactive oxygen species. These diverse functions have lead to the hypothesis that WAVE proteins have multi-functional roles in regulating cancer invasiveness, metastasis, development of tumor vasculature and angiogenesis. Differentials in expression of WAVE proteins are associated with a number of neoplasms include colorectal cancer, hepatocellular cancer, lung squamous cell carcinoma, human breast adenocarcinoma and prostate cancer. In this review we attempt to unify our knowledge regarding WAVE proteins, focusing on their potentials as diagnostic markers and molecular targets for cancer therapy.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.62-67
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• 2012

TNF-related apoptosis-inducing ligand (TRAIL) is a promising agent for management of cancer because of its selective cytotoxicity to cancer cells. However, some cancer cells have resistance to TRAIL. Accordingly, novel treatment strategies are required to overcome TRAIL resistance. Here, we examined the synergistic apoptotic effect of apigenin in combination with TRAIL in Huh-7 cells. We found that combined treatment of TRAIL and apigenin markedly inhibited Huh-7 cell growth compared to either agent alone by inducing apoptosis. Combined treatment with apigenin and TRAIL induced chromatin condensation and the cleavage of poly (ADP-ribose) polymerase (PARP). In addition, enhanced apoptosis by TRAIL/apigenin combination was quantified by annexin V/PI flow cytometry analysis. Western blot analysis suggested that apigenin sensitizes cells to TRAIL-induced apoptosis by activating both intrinsic and extrinsic apoptotic pathway-related caspases. The augmented apoptotic effect by TRAIL/apigenin combination was accompanied by triggering mitochondria-dependent signaling pathway, as indicated by Bax/Bcl-2 ratio up-regulation. Our results demonstrate that combination of TRAIL and apigenin facilitates apoptosis in Huh-7 cells.

• Journal of Life Science
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• v.11 no.1
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• pp.48-53
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• 2001

This study was performed to observe the cytotoxic effect of the various salted fish extracts against cancer cell line, human hepatocellular carcinoma (HepG2) using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) method. Urechis unicinctus was the strongest cytotoxic effects among any other traditional salted fish products. The growth inhibition ratio of Urechis unicinctus hot-water extracts was 94.5% at the concentration of 1000$\mu\textrm{g}$/$m\ell$. On the other hand, in case of salted fish methanol extracts, salt-fermented shad gizzard was showed the strongest cytotoxic effects. The growth inhibition ratio of salt-fermented shad gizzard methanol extracts was investigated 90% at the concentration of 1000$\mu\textrm{g}$/.$m\ell$.

• YAKHAK HOEJI
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• v.56 no.1
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• pp.35-41
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• 2012

In this study, we examined the effect of luteolin to enhance TRAIL-induced anticancer effect in SK-Hep1 cells. We found that combined use of TRAIL with luteolin markedly enhanced the cytotoxicity compared to either agent alone by inducing apoptosis. Furthermore, combined treatment of TRAIL with luteolin significantly induced activation of death receptor pathway-related proteins as well as PARP-cleavage and activation of effector caspases. Also, our result indicated that upregulation of DR4 and DR5 by luteolin combination may contribute to enhanced susceptibility of SK-Hep1 cells to TRAIL.

• Proceedings of the Korean Society of Life Science Conference
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• 2007.10a
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• pp.41.1-41.1
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• 2007

See Full Text

• Proceedings of the Korean Society of Life Science Conference
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• 2001.02a
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• pp.77-77
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• 2001

• Food Science and Preservation
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• v.15 no.2
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• pp.274-279
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• 2008

This study investigated the antimutagenic and anticancer effects of soybean sauce (kanjang) supplemented with deep sea water and Sea Tangle. The Ames test indicated that kanjang had no mutagenicity but it significantly inhibited mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and 4-nitroquinoline-1-oxide (4NQO). Kanjang (200 ug/plate) with supplementary deep sea water and Sea Tangle had approximately 90.9% and 62.0% inhibitory effect, respectively, against mutagenesis of TA100 induced by MNNG and 4NQO. There was 61.7% inhibition of mutagenesis induced by 4NQO against the TA98 strain. Kanjang inhibited growth of cell lines of human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human gastric carcinoma (AGS), human lung carcinoma (A549), and human breast adenocarcinoma (MCF-7) in a concentration-dependent manner. Treatment with kanjang supplemented with 1.0 mg/mL deep sea water had cytotoxicities of 69.4% 70.5% 55.6% 82.1 % and 73.2% against HeLa, Hep3B, AGS, A549 and MCF-7 cells respectively. In contrast kanjang supplemented with 1 mg/mL deep sea water had only $10{\sim}40%$ cytotoxicity on normal human embryonal kidney cells (293). Kanjang supplemented with deep sea water significantly inhibited tumor growth in mice injected sarcoma-180 cells. In particular, kanjang supplemented with deep sea water (25 mg/kg) inhibited tumor cell activity by 40.9%.