• The Korea Journal of Herbology
• /
• v.39 no.5
• /
• pp.9-17
• /
• 2024

Objectives : Edible insects are the widely distributed group of animals and contain high quality proteins, fatty acids and minerals. In particular, insects are a possible interesting source of essential amino acids. Insects as traditional medicines have much potential as pharmaceuticals in modern medicines including treating infections, cancer, dissolving phlegm, relieving spasms, and inflammatory diseases. The aim of this study is to investigate the immunomodulatory effect of several kinds of insects and major amino acids. Methods : In our review we try to show the potential usefulness of insects and amino acids in searching for new therapeutic solutions for immunologic diseases. We summarized the knowledge about properties, usefulness of insect and amino acids in drug design. We hypothesized that insects and amino acids, their major ingredients, regulates airway inflammation and immunologic diseases and can be developed as therapeutic drugs for the treatment of immunologic diseases. Results : Several insects including Bombyx mori, Cryptotympana pustulata, Holotrichia diomphalia, Locusta migratoria, etc. and amino acids such as glutamine, glutamic acid, methionine and glycine may have potential protective effects against asthma and airway neutrophilia. Glutamic acid, cystine, methionine and glycine which contribute to glutathione metabolism, which are important anti-oxidant amino acids that may affect susceptibility to asthma. Conclusions : Our results provide evidence about the potential usefulness of several insects and their amino acids in allergic disorders. These findings suggest that several insects and amino acids have important roles in the way they affect the immune system and allergic responses.

• Journal of Applied Biological Chemistry
• /
• v.58 no.3
• /
• pp.219-226
• /
• 2015

The anticancer activity of a methanolic extract from lemon leaves (MLL) was assessed in MCF-7-SC human breast cancer stem cells. MLL induced apoptosis in MCF-7-SC, as evidenced by increased apoptotic body formation, sub-G1 cell population, annexin V-positive cells, Bax/Bcl-2 ratio, as well as proteolytic activation of caspase-9 and caspase-3, and degradation of poly (ADP-ribose) polymerase (PARP) protein. Concomitantly, MLL induced the formation of acidic vesicular organelles, increased LC3-II accumulation, and reduced the activation of Akt, mTOR, and p70S6K, suggesting that MLL initiates an autophagic progression in MCF-7-SC via the Akt/mTOR pathway. Epithelial-mesenchymal transition (EMT), a critical step in the acquisition of the metastatic state, is an attractive target for therapeutic interventions directed against tumor metastasis. At low concentrations, MLL induced anti-metastatic effects on MCF-7-SC by inhibiting the EMT process. Exposure to MLL also led to an increase in the epithelial marker E-cadherin, but decreased protein levels of the mesenchymal markers Snail and Slug. Collectively, this study provides evidence that lemon leaves possess cytotoxicity and anti-metastatic properties. Therefore, MLL may prove to be beneficial as a medicinal plant for alternative novel anticancer drugs and nutraceutical products.

• Toxicological Research
• /
• v.34 no.2
• /
• pp.133-141
• /
• 2018

Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that $10{\mu}M$ cynaroside diminished cisplatin-induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells. To confirm the effect of cynaroside on cisplatin-induced kidney injury in vivo, we used cisplatin exposure animal model (20 mg/kg, balb/c mice, i.p., once a day for 3 days). Renal dysfunction, tubular damage and neutrophilia induced by cisplatin injection were decreased by cynaroside (10 mg/kg, i.p., once a day for 3 days). Results indicated that cynaroside decreased cisplatin-induced kidney injury in vitro and in vivo, and it could be used for improving cisplatin-induced side effects. However, further experiments are required regarding toxicity by high dose cynaroside and caspase-3/MST-1-linked signal transduction in the animal model.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.6
• /
• pp.2619-2623
• /
• 2014

Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

• Biomolecules & Therapeutics
• /
• v.21 no.3
• /
• pp.190-195
• /
• 2013

Cisplatin is a member of platinum-containing anti-cancer drugs that causes cross-linking of DNA and ultimately cancer cell apoptosis. The therapeutic function of cisplatin on various types of cancers has been widely reported but the side effects have been discovered together and nephrotoxicity has been regarded as major side effect of cisplatin. To select candidates for new sensitive nephrotoxicity biomarker, we performed proteomic analysis using 2-DE/MALDI-TOF-MS followed by cisplatin treatment in human kidney cell line, HK-2 cells, and compared the results to the gene profile from microarray composed of genes changed in expression by cisplatin from formerly reported article. Annexin A5 has been selected to be the most potential candidate and it has been identified using Western blot, RT-PCR and cell viability assay whether annexin A5 is available to be a sensitive nephrotoxic biomarker. Treatment with cisplatin on HK-2 cells caused the increase of annexin A5 expression in protein and mRNA levels. Over-expression of annexin A5 blocked HK-2 cell proliferation, indicating correlation between annexin A5 and renal cell toxicity. Taken together, these results suggest the possibility of annexin A5 as a new biomarker for cisplatin-mediated nephrotoxicity.

• Korean Journal of Acupuncture
• /
• v.22 no.3
• /
• pp.165-174
• /
• 2005

Objective : The objective of this study is to investigate the inhibitor effects of an traditional oriental herb, Sophora flavescens on the hepatic and renal side effects of chemotherapy by using B16-BL6 melanoma-injected C57BL6 mouse tumor model. Methods : In this study, the effects of an traditional oriental herb, Sophora flavescens, on the side effects of chemotherapy were studied using B16 melanoma-injected C57BL6 mouse tumor model. Results : Sophora flavescen has significant effect on the reduction of the side effects of chemotherapy. Sophora flavescen recovered the reduction of WBC and RBC during cisplatin chemotherapy. Water extract of Sophora flavescens significantly inhibited cisplatin-induced increase of serum blood urea nitrogen (BUN) which is a good indicator of renal toxicity. Sophora flavescens extract does not decrease the anti-tumor activity of cisplatin showing that it can selectively inhibit side effects of anticancer drugs preserving beneficial effort. Conclusion : Theses results suggest a possibility that Sophora flavescens extract can be used for cancer patients for the reduction of the side effects and improving the quality of life during chemotherapy of cancer patients.

• Molecules and Cells
• /
• v.26 no.1
• /
• pp.93-99
• /
• 2008

Transcriptional silencing is regulated by promoter methylation and histone modifications such as methylation and acetylation. We constructed a Schizosaccaromyces pombe reporter strain, KCT120a, to identify modifiers of transcriptional silencing, by inserting the $ura4^+$ gene into a heterochromatic telomere region. Two compounds inhibited the activity of histone deacetylases, induced acetylation of histone H3 and caused apoptotic cell death in HeLa cells. Expression of gelsolin and $p21^{waf1/cip1}$ also increased, as it does in response to HDAC inhibitors such as TSA. Therefore, these compounds appear to be potent inhibitors of HDACs, and hence potential anti-cancer drugs. Our observations suggest that a yeast cell-based assay system for transcriptional silencing may be useful for identifying histone deacetylase inhibitors and other agents affecting chromatin remodeling.

• The Korean Journal of Physiology and Pharmacology
• /
• v.3 no.1
• /
• pp.75-82
• /
• 1999

It has been reported that activation of sphingomyelin pathway and nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit the promotion of colon carcinoma. Ceramide, a metabolite of sphingomyelin, and indomethacin were shown to induce apoptosis in colon carcinoma cells. However, the mechanisms of ceramide- and indomethacin-induced apoptosis in the colon carcinoma cells are not clearly elucidated. Recent studys showed that indomethacin-induced apoptosis in colon cancer cells through the cyclooxygenase-independent pathways, and that may be mediated by generation of ceramide. In this study, we compared effects of ceramide and indomethacin on important modulators of apoptotic processes in HT29 cells, a human colon cancer cell line. Ceramide and indomethacin induced apoptosis dose- and time- dependently. Ceramide and indomethacin increased stress-activated protein kinase (SAPK) activity, and decreased mitogen-activated protein kinase (MAPK) activity. The expression of Bak was increased by the treatment of ceramide and indomethacin. The expression of other Bcl-2 related proteins (Mcl-1, $Bcl-X_L,$ Bax) which were known to be expressed in colon epithelial cells was not changed during the ceramide- and indomethacin-induced apoptosis. Our results suggest that ceramide and indomethacin share common mechanisms for induction of apoptosis in HT29 cells.

• Tuberculosis and Respiratory Diseases
• /
• v.56 no.2
• /
• pp.169-177
• /
• 2004

Background : Cyclooxygenase is the main target enzyme for the nonsteroidal anti inflammatory drugs (NSAIDs) that have been shown to suppress carcinogenesis in both experimental models and epidemiological studies. COX-2 plays an important role in solid tumor growth, invasiveness and angiogenesis, through, in part, the synthesis of prostaglandins, such as prostaglandin E2 (PGE2). In this study, the prognostic significance of an increase in COX-2 expression in lung cancer samples was evaluated. Material and Methods : The expression of COX-2, by immunohistochemistry, was studied in paraffin-embedded tumor blocks obtained from 84 patients(male 67, female 17, with a mean age of 63, ranging from 34 to 84 years) who had undergone surgery at Wonkwang University Hospital, between 1997 and 2002. For the evaluation of the relationships between COX-2 expression, and the clinical stage, metastasis to lymph nodes and survival, those cases showing the respective antigen expression in >10% of the tumor cells were considered positive. Result : Of the 84 patients, 61 (73%) exhibited more than 10% COX-2 immunoreactivities in the tumor and normal cells, whereas the remaining 23 showed no increase in the expression of COX-2. There was no significant relationship between the increased expression of COX-2 and the disease stage(p=0.1002) or cell type(p=0.152). The median survival was longer for the patients with a negative, compared to positive, COX-2 expression(36 compared to 24 months, p<0.05). The two year-survival rate was also higher in the patients with a negative COX-2 expression (78%) than those with a positive expression (47%, Kaplan-Meier, Log Rank, p < 0.05). Conclusion : The median survival was longer in the patients with a negative, compared to positive, COX-2 expression was longer than those with positive COX-2, having undergone complete resection due to primary non-small cell lung cancer.

• Journal of Life Science
• /
• v.14 no.3
• /
• pp.445-452
• /
• 2004

We investigated the cytotoxic effects of seven furanoterpenoids 〔sarcotin A, epi-sarcotin A, ircinin-1, epi-sarcotrine B, sarcotin I, (8E, l3Z, 20Z)-strobilinin/(7E,l3Z, 20Z)-felixinin and (7E,12E,18R,20Z)-variabilin〕 isolated from the sponge Sarcotragus sp. (the order Dictyoceratida) on the growth of A549 human lung carcinoma cells. MTT data revealed that sarcotin A and (7E,12E,18R,20Z)-variabilin exhibited higher potencies on the anti-proliferative activities than the other compounds in A549 cells. The growth inhibition by treatment with compounds (especially epi-sarcotin A, ircinin-1 and epi-sarcotrine B) were associated with the induction of apoptotic cell death through the concentration-dependent increase of Bax/Bcl-2 ratio in a p53-dependent or independent pathway Additionally, epi-sarcotin A and ircinin-1 strongly inhibited the levels of cyclooxygenase (COX)-2 expression without alteration of COX-1. Taken together, the results suggest that the furanoterpenoids from the marine sponge have strong potentials as candidates for anti-cancer drugs.