• Biomolecules & Therapeutics
• /
• v.27 no.2
• /
• pp.216-221
• /
• 2019

The c-Met protein is a receptor tyrosine kinase involved in cell growth, proliferation, survival, and angiogenesis of several human tumors. Overexpression of c-Met has been found in gastric cancers and correlated with a poor prognosis. Indirubin is the active component of Danggui Longhui Wan, which is a traditional Chinese antileukemic recipe. In the present study, we tested the anti-cancer effects of an indirubin derivative, LDD-1937, on human gastric cancer cells SNU-638. When we performed the in vitro kinase assay against the c-Met activity, LDD-1937 inhibited the activity of c-Met. This result was confirmed by immunoblot and immunofluorescence of phosphorylated c-Met. Immunoblot analysis showed that LDD-1937 decreased the expression of the Erk1/2, STAT3, STAT5, and Akt, downstream proteins of c-Met. In addition, LDD-1937 reduced the cell viability and suppressed colony formation and migration of SNU-638 cells. Furthermore, LDD-1937 induced $G_2/M$ phase arrest in the SNU-638 cells by decreasing the expression levels of cyclin B1 and CDC2. Cleaved-PARP, an apoptosis-related protein, was up-regulated in cells treated with LDD-1937. Overall, this study suggests that LDD-1937 may be a novel small-molecule with therapeutic potential for selectively inhibiting c-Met and c-Met downstream pathways in human gastric cancers overexpressing c-Met.

• Journal of Microbiology and Biotechnology
• /
• v.31 no.6
• /
• pp.775-783
• /
• 2021

Sea cucumber, Holothuria scabra, is a well-known traditional Asian medicine that has been used for suppressing inflammation, promoting wound healing, and improving immunity. Moreover, previous studies demonstrated that the extract from H. scabra contains many bioactive compounds with potent inhibitory effect on tumor cell survival and progression. However, the effect of the methanolic extract from the body wall of H. scabra (BWMT) on human prostate cancer cells has not yet been investigated. In this study, we aimed to investigate the effects and underlying mechanism of BWMT on prostate cancer cell viability and metastasis. BWMT was obtained by maceration with methanol. The effect of BWMT on cell viability was assessed by MTT and colony formation assays. The intracellular ROS accumulation was evaluated using a DCFH-DA fluorescence probe. Hoechst 33342 staining and Annexin V-FITC/PI staining were used to examine the apoptotic-inducing effect of the extract. A transwell migration assay was performed to determine the anti-metastasis effect. BWMT significantly reduced cell viability and triggered cellular apoptosis by accumulating intracellular ROS resulting in the upregulation of JNK and p38 signaling pathways. In addition, BWMT also inhibited the invasion of PC3 cells by downregulating MMP-2/-9 expression via the ERK pathway. Consequently, our study provides BWMT from H. scabra as a putative therapeutic agent that could be applicable against prostate cancer progression.

• Journal of Nutrition and Health
• /
• v.55 no.1
• /
• pp.47-58
• /
• 2022

Purpose: Obesity and a high-fat diet (HFD) are risk factors for colorectal cancer. We have previously shown that luteolin (LUT) supplementation in HFD-fed mice markedly inhibits tumor development in chemically induced colon carcinogenesis. In this study, we evaluated the anticancer effect of LUT in the inhibition of cell proliferation in HFD-fed obese mice and HT-29 human colorectal adenocarcinoma cells grown in an adipocyte-derived medium. Methods: C57BL/6 mice were fed a normal diet (ND, 11.69% fat out of total calories consumed, n = 10), HFD (40% fat out of total calories consumed, n = 10), HFD with 0.0025% LUT (n = 10), and HFD with 0.005% LUT (n = 10) and were subjected to azoxymethane-dextran sulfate sodium chemical colon carcinogenesis. All mice were fed the experimental diet for 11 weeks. 3T3-L1 preadipocytes and HT-29 cells were treated with various doses of LUT in an adipocyte-conditioned medium (Ad-CM). Results: The weekly body weight changes in the LUT groups were similar to those in the HFD group; however, the survival rates of the LUT group were higher than those of the HFD group. Impaired crypt integrity of the colonic mucosa in the HFD group was observed to be restored in the LUT group. The colonic expression of proliferating cell nuclear antigen and insulin-like growth factor 1 (IGF-1) receptors were suppressed by the LUT supplementation in the HFD-fed mice. The LUT treatment (10, 20, and 40 µM) inhibited the proliferation and migration of HT-29 cells cultured in Ad-CM in a dose-dependent manner, as well as the differentiation of 3T3-L1 preadipocytes. Conclusion: These results suggest that the anticancer effect of LUT is probably due to the inhibition of IGF-1 signaling and adipogenesis-related cell proliferation in colon cancer cells.

• Parasites, Hosts and Diseases
• /
• v.60 no.2
• /
• pp.117-126
• /
• 2022

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

• Journal of Chest Surgery
• /
• v.55 no.6
• /
• pp.470-477
• /
• 2022

Background: Upfront surgery followed by systemic treatment is recommended to treat clinical stage I-IIA small cell lung cancer (SCLC), but data on the clinical outcomes are sparse. Thus, this study evaluated the stage migration and long-term prognosis of surgically treated clinical stage I-IIA SCLC. Methods: We retrospectively reviewed 49 patients with clinical stage I-IIA SCLC who underwent upfront surgery between 2000 and 2020. Additionally, we re-evaluated the TNM (tumor-node-metastasis) staging according to the eighth edition of the American Joint Committee on Cancer staging system for lung cancer. Results: The clinical stages of SCLC were cIA in 75.5%, cIB in 18.4%, and cIIA in 6.1% of patients. A preoperative histologic diagnosis was made in 65.3% of patients. Lobectomy and systematic lymph node dissection were performed in 77.6% and 83.7% of patients, respectively. The pathological stages were pI in 67.3%, pII in 24.5%, pIII in 4.1%, and pIV in 4.1% of patients. The concordance rate between clinical and pathological stages was 44.9%, and the upstaging rate was 49.0%. The 5-year overall survival (OS) rate was 67.8%. No significant difference in OS was found between stages pI and pII. However, the OS for stages pIII/IV was significantly worse than for stages pI/II (p<0.001). Conclusion: In clinical stage I-IIA SCLC, approximately half of the patients were pathologically upstaged, and OS was favorable after upfront surgery, particularly in pI/II patients. The poor prognosis of pIII/IV patients indicates the necessity of intensive preoperative pathologic mediastinal staging.

• The Korea Journal of Herbology
• /
• v.27 no.6
• /
• pp.7-13
• /
• 2012

Objectives : Reactive oxygen species (ROS) have been associated with pathogenic processes including carcinogenesis through direct effect on DNA directly and by acting as a tumor promoter. Therefore, it has been regarded that ROS may be a major target for cancer prevention. The root of Paeonia lactiflora pall (PL), a traditional Chinese herb, has been a component of effective prescriptions for treatment of liver disease. Also, there are some reports about the antioxidant activities of the extracts from PL. However, little has been known about the effects of PL against oxidative damage. This work aimed to elucidate the anti-oxidant effects of Paeonia lactiflora pall (PL) in the non-cellular system and cellular system. Methods : Antioxidant activities of PL were evaluated by hydroxyl radical scavenging assay and $Fe^{2+}$ chelating assay. Anti-oxidative effect of PL was evaluated by ${\varphi}X$-174 RF I plasmid DNA cleavage assay in non-cellular system. In addition, DNA migration assay, expression level of phospho-H2AX, MTT assay and lipid peroxidation assay were performed for evaluate the anti-oxidative effect of PL in cellular system. Results : PL had a dose-dependent hydroxyl radical scavenging and $Fe^{2+}$ chelating capacity. In addition, PL inhibited oxidative DNA and cell damage induced by hydroxyl radical in non-cellular system and cellular system. Conclusion : Taken together, P. lactiflora pall may be possible for the application to a potential drug for treating the oxidative diseases such as cancer.

• BMB Reports
• /
• v.55 no.6
• /
• pp.281-286
• /
• 2022

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSC-markers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogene-derived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis.

• Nutrition Research and Practice
• /
• v.17 no.5
• /
• pp.855-869
• /
• 2023

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of Lycium barbarum leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity. MATERIALS/METHODS: AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells. RESULTS: Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 ㎍/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells. CONCLUSIONS: These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant. Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.

• The Korean Journal of Physiology and Pharmacology
• /
• v.28 no.3
• /
• pp.219-227
• /
• 2024

Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activity while high concentration of IC₅₀ at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.

• Journal of Gastric Cancer
• /
• v.7 no.2
• /
• pp.82-87
• /
• 2007

Purpose: In gastric cancer patients with gastric outlet obstruction, there are several complications such as malnutrition and vomiting. Palliative enteral stenting is a less invasive procedure as compared with a gastrojejunostomy. The aim of this study was to determine whether there was a significant difference between patients that undergone palliative enteral slanting and patients that had received a bypass gastrojejunostomy. Materials and Methods: One hundred patients underwent palliative entering stenting and 3f patients were subjected to a surgical bypass gastrojejunostomy. We reviewed the medical records of the patients with gastric outlet obstruction secondary to far advanced gastric cancer that were diagnosed using a gastrofibroscope, UGI and abdominal CT, and were admitted to our institution between January 2000 and August 2006. The outcome of stent placement for gastric outlet obstruction was compared with palliative gastrojejunostomy during the same period. We excluded patients with recurrent gastric cancer and double cancer from this study. Results: There were significant differences between the group of patients that underwent slanting and the group of patients that received a gastrojejunostomy regarding the age of patients ($67{\pm}12$ vs. $57{\pm}9$, P<0.001) but not between the sex of the patients (M : F, 2 : 1 vs. 2 :1, P=0.637). The most common complication of stenting was tumor ingrowth (16/100, 16%) and the second most common complication was stent migration (14/100). Failure of the procedure occurred in only three patients. Twenty-three patients underwent re-slanting and one patient required open conversion with a gastrojejunostomy. The median time to the first meal was $4{\pm}2$ days in the stent group of patients and $6{\pm}2$ days in the gastrojejunostomy group of patients (P=0.001). The median postoperative hospital stays were 9 days in the stent group of patients and 15 days in the gastrojejunostomy group of patients (P=0.003). The mean survival periods were 11 months in the stent group of patients and 10 months in the gastrojejunostomy group of patients (P=0.937). Conclusion: There were no significant differences In the mean survival rates. An earlier first meal and a shorter hospitalization stay were found in the slanting group of patients compared to the bypass gastrojejunostomy group of patients. However, re-slanting was a concern due to tumor ingrowth and stent migration.