• Journal of Life Science
• /
• v.34 no.5
• /
• pp.287-295
• /
• 2024

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide, necessitating novel therapeutic strategies. The chemotherapeutic agents used to treat HCC patients are toxic and have serious side effects. Therefore, we investigated the efficacy of anticancer drugs that reduce side effects by targeting tumor cells without causing cytotoxicity in healthy hepatocytes. Berberine, an isoquinoline alkaloid derived from plant compounds, has emerged as a potential candidate for cancer treatment due to its diverse pharmacological properties. The effect of berberine on HepG2 cell viability was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. HepG2 cell proliferation was determined through a colony-forming assay. The effects of berberine on HepG2 cell migration were evaluated using a wound-healing assay. Berberine inhibited the proliferation of HepG2 cells, as well as colony formation and migration. Berberine treatment increased the expression of autophagy-related genes and proteins, including Beclin-1 and LC3-II, and elevated the activities and mRNA expression of Caspase-9 and Caspase-3. Additionally, in experiments utilizing the Cell-Derived Xenograft animal model, berberine treatment reduced tumor size and weight in a concentration-dependent manner. These results demonstrate the potential of berberine as a versatile anticancer agent with efficacy in both cellular and animal models of hepatocellular carcinoma. The findings herein shed light on berberine's efficacy against HCC, presenting opportunities for targeted and personalized therapeutic interventions.

• Journal of Applied Biological Chemistry
• /
• v.55 no.3
• /
• pp.157-161
• /
• 2012

The aim of this research was to investigate the industrial application of Sedum sarmentosum. Antibacterial activities of the n-hexane, methylene chloride (MC), ethyl acetate, and n-butanol fractions of S. sarmentosum were tested against Escherichia coli, Staphylococcus aureus, and Helicobacter pylori. The MC fraction showed the strongest antibacterial activity against E. coli, with an inhibition zone greater than 13 mm in disc assays. At $100{\mu}g/mL$, all fractions scavenged more than 50% of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals (${\cdot}OH$). In particular, the MC fraction showed the strongest scavenging activity against DPPH and ${\cdot}OH$. In addition, we found that treatment with the MC fraction inhibited the growth of H. pylori and gastric adenocarcinoma cells. The present results suggest that the MC fraction of S. sarmentosum would play the promising protective role against pathogenic bacteria and free radicals.

• Animal cells and systems
• /
• v.5 no.4
• /
• pp.267-274
• /
• 2001

Calpains are a family of cysteine proteases existing primarily in two forms designated by the $Ca^{2+}$ concentration needed for activation in vitro, $\mu$-calpain (calpain-I) and m-calpain (calpain-II). The physiologica1 roles of calpains remain unclear. Many groups have proposed a role for calpains In apoptosis, but their patterns of activation are not well characterized. Calpains have been implicated in neutrophil apoptosis, glucocorticoid-induced thymocyte apoptosis, as well as many other apoptotic pathways. Calpain activation in apoptosis is usually linked upstream or downstream to caspase activation, or in a parallel pathway alongside caspase activation. Calpains have been suggested to be involved in DNA fragmentation (via endonuclease activation), but also as effector proteases that cleave cellular proteins involved in DNA repair, membrane associated proteins and other homeostatic regulatory proteins. Recently, our laboratory demonstrated $\mu$-calpain activation in NAD(P)H: quinone oxidoreducatse 1 (NQO1)-expressing cells after exposure to $\beta$-lapachone, a novel quinone and potential chemo- and radio-therapeutic agent. Increased cytosolic $Ca^{2+}$ in NQO1-expressing cells after $\beta$-lapachone exposures were shown to lead to $\mu$-calpain activation. In turn, $\mu$-calpain activation was important for substrate proteolysis and DNA fragmentation associated with apoptosis. Upon activation, $\mu$-calpain translocated to the nucleus where it could proteolytically cleave PARP and p53. We provided evidence that $\beta$-lapachone-induced, $\mu$-calpain stimulated, apoptosis did not involve any of the known caspases; known apoptotic caspases were not activated after $\beta$-lapachone treatment of NQO1-expressing cells, nor did caspase inhibitors have any effect on $\beta$-1apachone-induced cell death. Elucidation of processes by which $\beta$-1apachone-stimulated $\mu$-calpain activation and calpains ability to activate endonucleases and induce apoptosis independent of caspase activity will be needed to further develop/modulate $\beta$-lapachone for treatment of human cancers that over-express NQO1.

• Journal of Korean Medicine for Obesity Research
• /
• v.24 no.1
• /
• pp.41-53
• /
• 2024

Objectives: We used the Korea Health Panel Annual Data 2019 to analyze factors related to visits to both Korean medicine and Western medicine (WM) outpatient clinics among patients with overweight and obesity. Methods: The inclusion criteria for this study are as follows: 1) adults over 18 years of age, 2) overweight or obese with a body mass index of 25.0 or more, 3) visited WM outpatient clinics at least once during 2019. Total 2,963 individuals were included in WM group or integrative medicine (IM) group. Using the Andersen healthcare utilization model, factors related to healthcare utilization of the participants were classified. Binomial logistic regression analysis was used to analyze factors associated with IM use. Results: Among the participants, 80.49% (n=2,385) were assigned to WM group and 19.51% (n=578) to IM group. As a result of the regression analysis, factors significantly related to the use of IM included the elderly over 65 years of age, sex (men), college or higher education level, residential area (Gwangju/Jeolla/Jeju), presence of cancer, and presence of musculoskeletal disease. The main diagnosis associated with both WM and IM use was most frequently musculoskeletal conditions. Also, IM group received WM treatment for musculoskeletal conditions more frequently compared to WM group. Conclusions: This study is the first to analyze healthcare utilization patterns among overweight or obese patients in Korea. The current findings suggest that the presence of musculoskeletal conditions, especially in this population, may be strongly associated with concurrent use of IM services.

• Current Optics and Photonics
• /
• v.1 no.1
• /
• pp.51-59
• /
• 2017

In addition to its typical use for skin rejuvenation, fractional laser irradiation of early cancerous lesions may reduce the risk of tumor development as a byproduct of wound healing in the stroma after the controlled injury. While fractional ablative lasers are commonly used for cosmetic/aesthetic purposes (e.g., photorejuvenation, hair removal, and scar reduction), we propose a novel use of such laser treatments as a stromal treatment to delay tumorigenesis and suppress carcinogenesis. In this study, we found that non-ablative fractional laser (NAFL) irradiation may have a possible suppressive effect on early tumor growth in syngeneic mouse tumor models. We included two syngeneic mouse tumor models in irradiation groups and control groups. In the irradiation group, a thulium fiber based NAFL at 1927 nm was used to irradiate the skin area including the tumor injection region with 70 mJ/spot, while no laser irradiation was applied to the control group. Numerical simulation with the same experimental condition showed that thermal damage was confined only to the irradiation spots, sparing the adjacent tissue area. The irradiation groups of both tumor models showed smaller tumor volumes than the control group at an early tumor growth stage. We also detected elevated inflammatory cytokine levels a day after the NAFL irradiation. NAFL treatment of the stromal tissue could potentially be an alternative anticancer therapeutic modality for early tumorigenesis in a minimally invasive manner.

• Journal of Society of Preventive Korean Medicine
• /
• v.20 no.2
• /
• pp.97-109
• /
• 2016

Objectives : The effects of Jaeumkanghwatang (JEKHT) co-administration on the pharmacokinetics of tamoxifen were observed after oral combination treatment of tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day repeated oral pretreated rats with 8-day repeated co-administration to confirm the effects of JEKHT co-administration on the pharmacokinetics of tamoxifen. Methods : Six days after pretreatment of JEKHT 100 mg/kg, tamoxifen 50 mg/kg was co-administered with JEKHT 100 mg/kg, once a day for 8 days within 5 min. The blood were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 8th tamoxifen treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered. Results : Six-day repeated oral pretreatment of JEKHT and 8-day repeated oral co-administration of tamoxifen within 5 min did not influenced on the plasma concentrations and pharmacokinetic parameters of tamoxifen, oral bioavailability, as compared with tamoxifen single treated rats, except for some negligible effects. Conclusions : It is concluded that JEKHT did not influenced on the plasma concentrations and pharmacokinetic parameters, the oral bioavailability of tamoxifen. Therefore, it is considered that co-administration of JEKHT and tamoxifen will be provide an effective novel treatment regimen on the comprehensive and integrative medicine for breast cancer patients, if they showed favorable synergic effects on the pharmacodynamics or reduce the tamoxifen treatment related toxicity and side effects in future studies.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.26 no.2
• /
• pp.228-233
• /
• 2012

Two years ago, a 75-year-old female was diagnosed left renal cancer and went on radical nephrectomy. Recently, metastatized lesions on lumbar spine and various lymph nodes including paraaortic lymph node of which diameter was about 5.5 cm was identified. She suffered from extreme low back pain despite using opioid agents of fentanyl patch and oral oxycodone. During about one month, Korean medicine therpies including herbal medicine(Yang-He tang), acupuncture with her conventional medications were co-administered. However her pain didn't improved and gradual cough and dyspnea developed. So she transferred to the hemato-oncology part for 2 weeks under the diagnosis of everolimus-induced noninfectious pneumonitis. After quitting everolimus her pneumonitis was improved and she came back our ward and started another herbal medicine, Ai-Tong-Ning tang for about 2 months. During this period, her pain was well managed without oral opioid agents and her paraaortic lymph node was regressed to about 2.2cm in diameter.

• Animal cells and systems
• /
• v.8 no.1
• /
• pp.27-32
• /
• 2004

Endothellial cells are subjected to hemodynamic shear stress, the dragging force generated by blood flow. Shear stress regulates endothelial cell shape, structure, and function, including gene expression. Since endothelial cells must be anchored to their extracellular matrices(ECM) for their survival and growth, we hypothesized that ECMs are crucial for shear-dependent activation of extracellular signalactivated regulated kinase(ERK) that is important for cell proliferation. Shear stress-dependent activation of ERK was observed in cells plated on two different matrices, fibronectin and vitronectin(the two most physiologically relevant ECM in endothelial cells). We then treated bovine aortic endothelial cells(BAECs) with Arg-Gly-Asp(RGD) peptides that block the functional activation of integrin binding to fibronectin and vitronectin, and a nonfunctional peptide as a control. Treatment of cells with the RGD peptides, but not the control peptide, significantly inhibited ERK activity in a concentration-dependent manner. This supports the idea that integrin adhesion to the ligands, fibronectin and vitronectin, mediates shear stress-dependent activation of ERK. Subsequently, whereas antagonists of vitronectin(LM 609, an antibody for integrin ${\alpha}_{\gamma}$/${\beta}_3$ and XT 199, an antagonist specific for integrin ${\alpha}_{\gamma}$/${\beta}_3$) did not have any effect on shear-dependent activation of ERK, antagonists of fibronectin(a neutralizing antibody for integrin ${\alpha}_5$/${\beta}_1$or ${\alpha}_4$${\beta}_1$ and SM256) had an inhibitory effect. These results clearly demonstrate that mechanoactivation of ERK requires anchoring of endothelial cells to fibronectin through integrins.

• Journal of Sasang Constitutional Medicine
• /
• v.20 no.2
• /
• pp.164-170
• /
• 2008

1. Objectives This is a case of refractory ascites due to hepatocellular carcinoma treated with Sasang Constitutional Medication. Refractory ascites, which did not respond to diuretics, was improved with Jeoryeongchajeonja-tang. 2. Methods We recorded the patient's abdominal circumference, body weight and urine output daily. We also investigated the TTKG(transtubular potassium gradient) values 3 times during the treatment course. 3. Results the TTKG value of the patient was siginificantly decreased. TTKG values before administration of Jeotyeongchajeonja-tang were 8.41, 10.82, respectively and 4.25 after administration of Jeotyeongchajeonja-tang. 4. Conclusions We guess that Jeoryeongchajeonja-tang functions as an aldosterone antagonist or increases spironolactone activity through interaction between Jeotyeongchajeonja-tang and spironolactone. But the mechanism of Jeotyeongchajeonja-tang is not clear, so we need more clinical study of refractory ascites improved with Jeotyeongchajeonja-tang and biological study of interaction between Jeotyeongchajeonja-tang and spironolactone.

• Animal cells and systems
• /
• v.15 no.2
• /
• pp.139-146
• /
• 2011

Secretory leukocyte protease inhibitor (SLPI) plays an important role in promoting the invasion and metastasis of a range of cancer cells. However, there are no reports of the expression and function of SLPI in oral carcinoma cells. In this study, the oral carcinoma cell line KB was used to determine whether SLPI affects the proliferation, migration and invasion of oral carcinoma cells. RT-PCR and Western blotting revealed high levels of endogenous SLPI expression in KB cells as well as a strong increase in SLPI secretion after wounding compared to immortalized normal oral keratinocytes (INOK). The wound healing assay revealed more migration of KB cells than INOK cells, and the SLPI treatment increased the migration of KB cells. KB cell proliferation was increased significantly by the SLPI protein but decreased by SLPI-siRNA. SLPI strongly increased the migration and invasion of KB cells. On the other hand, SLPI-siRNA decreased the migration and invasion of KB cells. This suggests that SLPI plays an important role in the metastasis of oral carcinoma cells.