Ji-Youn Jung

Apoptotic Effect of Quercetin on HT-29 Colon Cancer Cells via the AMPK Signaling Pathway

Activation of AMP-activated protein kinase (AMPK), a physiological cellular energy sensor, strongly suppresses cell proliferation in both nonmalignant and tumor cells. This study demonstrates the mechanism of quercetin-induced apoptosis in HT-29 colon cancer cells. Treatment of cells with quercetin significantly decreased cell viability in a dose-dependent manner. Notably, quercetin increased cell cycle arrest in the G1 phase and up-regulated apoptosis-related proteins, such as AMPK, p53, and p21, within 48 h. Furthermore, in vivo experiments showed that quercetin treatment resulted in a significant reduction in tumor volume over 6 weeks, and apoptosis-related protein induction by quercetin was significantly higher in the 100 mg/kg treated group compared to the control group. All of these results indicate that quercetin induces apoptosis via AMPK activation and p53-dependent apoptotic cell death in HT-29 colon cancer cells and that it may be a potential chemopreventive or therapeutic agent against HT-29 colon cancer.

Blockade of Wnt/β-catenin signaling suppresses breast cancer metastasis by inhibiting CSC-like phenotype

The identification of cancer stem cells (CSCs) represents an important milestone in the understanding of chemodrug resistance and cancer recurrence. More specifically, some studies have suggested that potential metastasis-initiating cells (MICs) might be present within small CSC populations. The targeting and eradication of these cells represents a potential strategy for significantly improving clinical outcomes. A number of studies have suggested that dysregulation of Wnt/β-catenin signaling occurs in human breast cancer. Consistent with these findings, our previous data have shown that the relative level of Wnt/β-catenin signaling activity in breast cancer stem cells (BCSCs) is significantly higher than that in bulk cancer cells. These results suggest that BCSCs could be sensitive to therapeutic approaches targeting Wnt/β-catenin signaling pathway. In this context, abnormal Wnt/β-catenin signaling activity may be an important clinical feature of breast cancer and a predictor of poor survival. We therefore hypothesized that Wnt/β-catenin signaling might regulate self-renewal and CSC migration, thereby enabling metastasis and systemic tumor dissemination in breast cancer. Here, we investigated the effects of inhibiting Wnt/β-catenin signaling on cancer cell migratory potential by examining the expression of CSC-related genes, and we examined how this pathway links metastatic potential with tumor formation in vitro and in vivo.

Antitumor actions of baicalein and wogonin in HT-29 human colorectal cancer cells

The purpose of this study was to determine the effects of baicalein and wogonin, which are compounds derived from the Chinese herb Scutellaria baicalensis, in suppressing the viability of HT-29 human colon cancer cells. Following treatment with baicalein or wogonin, several apoptotic events were observed, including DNA fragmentation, chromatin condensation and increased cell cycle arrest in the G1 phase. Baicalein and wogonin decreased Bcl-2 expression, whereas the expression of Bax was increased in a dose-dependent manner compared with the control. Furthermore, the induction of apoptosis was accompanied by an inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt in a dose-dependent manner. The administration of baicalein to mice resulted in the inhibition of the growth of HT-29 xenografts without any toxicity following 5 weeks of treatment. The results indicated that baicalein induced apoptosis via Akt activation in a p53-dependent manner in the HT-29 colon cancer cells and that it may serve as a chemopreventive or therapeutic agent for HT-29 colon cancer.

Antiviral effect of korean red ginseng extract and ginsenosides on murine norovirus and feline calicivirus as surrogates for human norovirus.

Korean red ginseng has been studied various biological activities such as immune, anti-oxidative, anti-microbial, and anticancer activities but antiviral mechanism needs further studies. In this study, we aimed to examine the antiviral effects of Korea red ginseng extract and ginsenosides on norovirus surrogate, including murine norovirus (MNV) and feline calicivirus (FCV). We evaluated the pre-, co-, and post-treatment effects of Korean red ginseng (KRG), ginsenosides Rb1 and Rg1. To measure the antiviral effect and cytotoxicity of KRG extract, and ginsenosides Rb1 and Rg1, we treated Crandell-Reese Feline Kidney for FCV or RAW264.7 cells for MNV with concentrations of 0, 5, 6.7, 10, 20 ug/mL total saponin. There was cytotoxic effect in the highest concentration 20 ug/mL of KRG extract so this concentration was excluded in this study. The FCV titer was significantly reduced to 0.23-0.83 log10 50% tissue culture infectious dose (TCID50)/mL in groups pre-treated with red ginseng extract or ginsenosides. The titer of MNV was significantly reduced to 0.37-1.48 log10 TCID50/mL in groups pre-treated with red ginseng extract or ginsenosides. However, there was no observed antiviral effect in groups co-treated or post-treated with KRG and its constituents. Our data suggest that KRG extract has an antiviral effect against norovirus surrogates. The antiviral mechanisms of KRG and ginsenosides should be addressed in future studies.

Apoptotic effect of tolfenamic acid in androgen receptor-independent prostate cancer cell and xenograft tumor through specificity protein 1

Tolfenamic acid (Tol) is a non‐steroidal anti‐inflammatory drug that was reported to exhibit anticancer activity in pancreatic and colorectal cancer models. This study examined the role of Tol in the death regulation of PC‐3 and DU145 human androgen‐independent prostate cancer cells. The results showed that Tol inhibited cell growth and induced apoptosis, as evidenced by nuclear fragmentation and cleaved caspase 3 and poly(ADP‐ribose) polymerase. Tol suppressed the specificity protein 1 (Sp1) protein in both PC‐3 and DU145 cells. Tol also attenuated Sp1 mRNA and its promoter activity in DU145 cells, but did not alter them in PC‐3 cells, indicating that Tol degrades Sp1 protein in these cells. Tol also downregulated protein levels, mRNA levels and promoter activities of survivin and myeloid cell leukemia‐1, which are downstream targets of Sp1. The expressions of survivin and Mcl‐1 and cancer cell growth were lower in the PC‐3 cells treated with Sp1 interfering RNA and mithramycin A. Moreover, an oral injection of Tol decreased tumor growth and downregulated the Sp1 protein in athymic nude mice bearing DU145 cell xenografts without hepatotoxicity. Overall, Tol downregulates the Sp1 protein to inhibit growth and induce apoptosis in androgen‐refractory prostate cancers, both in vitro and in vivo, that show resistance against many chemotherapeutic agents. (Cancer Sci 2011; 102: 742–748)

Prevalence of Arcobacter Species Isolated from Retail Meats in Korea

This study was conducted to determine the prevalence of Arcobacter species identified or isolated from retail meats in Korea. Multiplex PCR assays for the detection of Arcobacter species were performed for 360 chicken, 100 pork, and 106 beef samples. Arcobacter butzleri and Arcobacter cryaerophilus were detected in 18.9 and 3.3% of chicken samples, respectively. However, Arcobacter species were not found in any of the pork and beef samples. Biochemical testing of isolates selected after enrichment revealed 38 A. butzleri isolates in chicken samples, but no A. cryaerophilus isolates were detected. In this study, A. butzleri was the most prevalent Arcobacter species in chicken meat, and contamination with Arcobacter species in pork and beef may be less prevalent in Korea.

Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer

Cervical cancer is the third most common cancer and the third leading cause of death among women. However, the standard treatment for cervical cancer includes cisplatin, which can cause side effects such as hematological damage or renal toxicity. New innovations in cervical cancer treatment focus on developing more effective and better-tolerated therapies such as Sp1-targeting drugs. Previous studies suggested that mithramycin A (Mith) inhibits the growth of various cancers by decreasing Sp1 protein. However, how Sp1 protein is decreased by Mith is not clear. Few studies have investigated the regulation of Sp1 protein by proteasome-dependent degradation as a possible control mechanism for the regulation of Sp1 in cancer cells. Here, we show that Mith decreased Sp1 protein by inducing proteasome-dependent degradation, thereby suppressing cervical cancer growth through a DR5/caspase-8/Bid signaling pathway. We found that prolonged Mith treatment was well tolerated after systemic administration to mice carrying cervical cancer cells. Reduction of body weight was minimal, indicating that Mith was a good therapeutic candidate for treatment of cancers in which Sp1 is involved in promoting and developing disease.

Chemopreventive effect of tolfenamic acid on KB human cervical cancer cells and tumor xenograft by downregulating specificity protein 1.

Earlier studies have shown that tolfenamic acid (Tol) exhibits anticancer activity in several cancer models by inhibiting tumor growth and angiogenesis. However, the chemopreventive effect of Tol on a cervical cancer model and the underlying mechanism of action are unknown. In this study, Tol was found to inhibit cell proliferation by inducing apoptosis without affecting cyclo-oxygenase 2 expression, but ampiroxicam did not. Tol decreases the specificity protein 1 (Sp1) mRNA and its promoter activity in KB cervical cancer cells, and the downregulation of Sp1 protein by affecting several proteins that contain GC-rich sites on their promoters. Studies using small interference RNA and an Sp1-specific inhibitor (mithramycin A) confirmed that the decrease in Sp1 by Tol affects survivin and p27. Tol also inhibited tumor growth and Sp1 protein in athymic nude mice xenografts. These results show that Tol could be a potent anticervical cancer drug that acts by regulating Sp1 protein and its downstream pathways.

Dihydroavenanthramide D inhibits human breast cancer cell invasion through suppression of MMP-9 expression.

Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-κB), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-κB and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis.

Ex vivo expansion of canine cytotoxic large granular lymphocytes exhibiting characteristics of natural killer cells.

Canine NK cells still are not well-characterized due to the lack of information concerning specific NK cell markers and the fact that NK cells are not an abundant cell population. In this study, we selectively expanded the canine cytotoxic large granular lymphocytes (CLGLs) that exhibit morphologic, genetic, and functional characteristics of NK cells from normal donor PBMCs. The cultured CLGLs were characterized by a high proportion of CD5(dim) expressing cells, of which the majority of cells co-expressed CD3 and CD8, but did not express TCRαβ and TCRγδ. The phenotype of the majority of the CLGLs was CD5(dim)CD3(+)CD8(+) TCRαβ(-)TCRγδ(-)CD4(-)CD21(-)CD11c(+/-)CD11d(+/-)CD44(+). The expression of mRNAs for NK cell-associated receptors (NKG2D, NKp30, NKp44, Ly49, perforin, and granzyme B) were highly upregulated in cultured CLGLs. Specifically, NKp46 was remarkably upregulated in the cultured CLGLs compared to PBMCs. The mRNAs for the NKT-associated iTCRα gene in CLGLs was present at a basal level. The cytotoxic activity of the CLGLs against canine NK cell-sensitive CTAC cells was remarkably elevated in a dose-dependent manner, and the CLGLs produced large amounts of IFN-γ. The antitumor activity of CLGLs extended to different types of canine tumor cells (CF41.Mg and K9TCC-pu-AXC) without specific antigen recognition. These results are consistent with prior reports, and strongly suggest that the selectively expanded CLGLs represent a population of canine NK cells. The results of this study will contribute to future research on canine NK cells as well as NK cell-based immunotherapy.