• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.385-392
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• 2006

Paclitaxel is an important chemotherapeutic agent for the treatment of human solid tumors. Multicellular resistance(MCR) is considered to be a major mechanism of resistance of human solid tumors to chemotherapeutic agent such as paclitaxel, which includes barriers to drug penetration through tumor tissues. Multicellular layers(MCL) cultures resemble in vivo tumor condition in terms of MCR and has been used successfully to produce clinically relevant data. In the present study, we evaluated the penetration characteristics and post-penetration anti-proliferative activity of paclitaxel using MCL of human colorectal cancer cells(DLD-1 and HT-29) grown in Transwell inserts. The penetration of $[^{14}C]-paclitaxel$ was slower than that of mannitol which penetrates via paracellular pathway in DLD-1 MCL. The penetration of $[^{14}C]-paclitaxel$ was faster in HT-29 MCL compared to DLD-1 MCL, i.e., at 10 ${\mu}M$ 100% and 40% penetration were observed after 48 hr incubation for HT-29 and DLD-1 cells, respectively. When calculated using anti-proliferative activity in the conditioned media of bottom chamber, the penetration after 24 hr was very limited(less than 50%) and concentration-dependent at the concentrations tested in both MCL's. These results suggest that limited and differential penetration of paclitaxel in tumor tissues may contribute to lower and differential efficacy against human solid tumors.

• Biomolecules & Therapeutics
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• v.14 no.2
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• pp.90-95
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• 2006

CKD-602 exerts its antitumor effect via inhibition of topoisomerase I in cancer cells. Multicellular spheroid (MCS) and Multicellular layers (MCLs) are known as in vitro 3-dimensional models which closely represent tumor conditions in vivo. In order to investigate the potential of CKD-602 against human colorectal tumors, we evaluated the anti-proliferative activity and penetration ability of CKD-602 in MCS and MCL cultures of DLD-l human colorectal cancer cells, respectively. The maximum effects($E_{max}$) induced by CKD-602 were significantly lower in MCS compared to monolayers (48% vs 92%). With prolonged drug exposure, the $IC_{50's}$ of CKD-602 decreased to $23.5{\pm}1.0nM$ in monolayers after 24 h exposure and $42.3{\pm}1.7nM$ in MCS after 6 days, respectively. However, no further increase in effect was observed for exposure time longer than growth doubling time (Td) in both cultures. Activity of CKD-602 was significantly reduced after penetration through MCL and also with cell-free insert membrane. In conclusion, CKD-602 showed significantly decreased anti-proliferative activity in 3D cultures (MCS) of human colorectal cancer cells. Tumor penetration of CKD-602 could not be determined due to loss of activity after penetration through cell free insert membrane, which warrants further evaluation using a modified model.

• Herbal Formula Science
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• v.15 no.1
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• pp.175-183
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• 2007

This study was conducted to evaluate the inhibitory effects of Yongseollan(YSL) on the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW264.7 cells. YSL is tropical plant originating from Mexico. The biological activity of this plant is not yet evaluated systematically. The aim of the present work is to investigate a potential anti-inflammatory activity of YSL. The RAW264.7 cells were cultured in D MEM/F12 medium for 24 hrs. After serum starvation, cells were treated with YSL for 1 hr, followed by stimulating NO production with a LPS. We found that YSL has an inhibitory effect on the production of NO, iNOS expression and $phospho-I{\kappa}B$ expression. YSL also inhibited tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-6, and $IL-1{\beta}$. Moreover, YSL inhibited cyclooxygenase (COX)-2 expression and prostanglandin E2 (PGE2). These findings showed that YSL could have some anti-inflammatory effects which might play a role in therapy in Gram-negative bacterial infections.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1805-1809
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• 2004

In order to validate the use of Radix Curcumae Aromaticae as an anti-inflammatory drug in the traditional Korean medicine, I have investigated the effect of water-soluble extract of Radix Curcumae Aromaticae (ECA) on the expression of inducible heme oxygenase-1 (HO-1), which ha.s anti-inflammatory and cytoprotective effects stimulates, in human umbilical vein endothelial cells (HUVECs) stimulated with a high dose of pro-inflammatory tumor necrosis factor-alpha (TNF-α). The extract protected dose-dependently HUVECs against TNF-α-induced apoptosis, as measured qualitatively by a nuclear staining method using the fluoresoence DAPI and quantitatively by a flow cytometry using fluoresce-enhanced Annexin V antibody, and significantly Increased HO-1 expression, as determined by Western blotting analysis using anti-HO-1 antibody. Biockage of HO-1 activity by a pharmacological inhibitor reversed cytoprotection afforded by the extract, and treatment with carbon monoxide, one of HO-1 metabolites, resulted in cytoprotection comparable to the extract. These results suggest that ECA may have therapeutic potential in the control of endothelial disorders caused by inflammatory cytokines.

• The Journal of Korean Medicine
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• v.26 no.4
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• pp.46-55
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• 2005

Objectives: This experimental study was carried out to evaluate the immune modulating and anti-tumor activity of Ampelopsis Radix extracts (ARE). Materials and Methods: To elucidate the effects of ARE on the macrophage and NK cell activity, we analyzed NO production, NK cytotoxicity and gene expressions of cytokine related with macrophage and NK cell activity. Results: ARE activated and promoted macrophages to product NO in part. And, ARE has significant properties to activate macrophages and NK cells by promoting related cytokines like IL-1, IL-12, IFN-$\gamma$, iNOS and TNF-$\alpha$ gene expressions. We also observed that ARE promoted protein expression of IFN-$\gamma$, and TNF-$\alpha$ in mice splenocytes. Conclusions: ARE is an effective herbal drug for immune modulating and anti-cancer by promoting activity of macrophages and NK cells.

• Journal of Medicine and Life Science
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• v.17 no.2
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• pp.41-46
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• 2020

Metformin, a predominantly prescribed anti-diabetic drug for decades, has gained new insights for its anti-tumor activity in a variety of cancer cells. Our previous studies also showed the obvious pro-apoptotic activity of metformin and the underlying action mechanisms in hepatocellular carcinoma cells. Together with apoptosis, autophagy is a crucial intracellular process to determine the survival or death of cells under some stressful environments. The present study aimed to determine the role of autophagy in metformin-induced death of H4IIE hepatocellular carcinoma cells. Metformin blocked the formation of autophagosome and the expression of LC3A, generally described as a biomarker of autophagy. Inhibition of AMPK reversed the metformin-induced blockade of autophagy. Antioxidant (NAC) suppressed the metformin-induced cell death but not affected LC3A. The inhibition of protein kinase C totally restored the metformin-suppressed expression of LC3A. In summary, our present study suggests that autophagy is an anti-apoptotic player in metformin-induced apoptosis in H4IIE cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.167-173
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• 2005

To investigate the possible molecular mechanism (s) of bee venom as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Bee venom treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Bee venom down-regulated the levels of anti-apoptotic genes such as Bcl-2 and Bcl-XS/L, however, the levels of Bax, a pro-apoptotic gene, were up-regulated. Bee venom treatment induced not only tumor suppressor p53 but also cyclin-dependent kinase inhibitor p21WAF1/CIP1 expression in a dose-dependent manner. Furthermore, bee venom treatment induced the down-regulation of telomerase reverse transcriptase mRNA and telomeric repeat binding factor expression of A549 cells, however, the levels of telomerase-associated protein-1 and c-myc were not affected. Taken together, these findings suggest that bee venom-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and bee venom may have therapeutic potential in human lung cancer.

• Natural Product Sciences
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• v.16 no.4
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• pp.259-264
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• 2010

The essential oil fraction was obtained from the underground parts o of Ligusticum chuanxiong (Umbelliferae) by steam distillation, and its main components, Z-ligustilide and butylidene phthalide, were isolated by column chromatography. Its essential oil fraction and the isolated main components were examined for effects on their anti-inflammatory properties in RAW 264.7 macrophage cells to develop a new natural anti-inflammatory drug. The results showed that the L. chuanxiong essential oil fraction and its main components, Z-ligustilide and butylidene phthalide, inhibited the production of nitric oxide significantly in lipopolysaccharide (LPS)-treated RAW 264.7 cells. LPS-induced interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-$\alpha$) production was also decreased in a dose-dependent manner. In addition, western blot analysis revealed that the L. chuanxiong essential oil fraction and also its main components, Z-ligustilide, and butylidene phthalide reduced the expression levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS).

• Proceedings of the Plant Resources Society of Korea Conference
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• 1999.10a
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• pp.58-64
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• 1999

As indicated by Chinese letters "사혁" (sha-ji) is the ripe fruit of Seabuckthron (Hippophae rhamnoides Linneus) Family Flaeagnaceae is one of ancient natural medicine used by the Tibetan and Mongolian nationallites with ancient methods to treat desease, It is an effectiv Traditional Tibetan medicine. Bud only now are they beginning to be understood in the world of modern medicine. Hippophae was written in the book of Traditional Tibetan Medicine - "Somalaza" (8th century), "Sibuyidian" (1840) and "Jingzhubencao" (Qing Dynasty). The "Sibuyidien" was trnslated in to the Russian and published at 1903 in the Russian. Then the Russian bigan to study on Hippophae and they have achieved great successes. The Chinese scientists began to study on the chemical constituent and medical action with modern technique at 1952. With more than 40 years painstaking eport they have conceived and used a wide variety of experimental screening systems, achieved successes. Finally the)1 with one's own tests has keen verified that the crude drug being various kind of bioactive substance could Inhibits tumor, increase immunity, wipe out free radical, prevent disease of cardiovascular system, have anti-radiation, anti-inflammeutory effects. At 1977 the Hippophae rhamnoides was written in Chinase Pharmacopoeia.e rhamnoides was written in Chinase Pharmacopoeia.

• Plant Resources
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• v.3 no.1
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• pp.93-97
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• 2000

As indicated by Chinese letters “沙赫” (sha-ji) is the ripe fruit of Seabuckthron(Hippophae rhamnoides Linneus) family Flaeagnaceae is one of ancient natural medicine used by the Tibetan and Mongolian nationallites with ancient methods to treat desease. It is an effectiv Traditional Tibetan medicine. Bud only now are they beginning to be understood in the world of modern medicine. Hippophae was written in the book of Traditional Tibetan Medicine - “Somalaza” (8th century), “Sibuyidian” (1840) and “Jingzhubencao” (Qing Dynasty). The “Sibuyidien” was trnslated in to the Russian and published at 1903 in the Russian. Then the Russian bigan to study on Hippophae and they have achieved great successes. The Chinese scientists began to study on the chemical constituent and medical action with modern technique at 1952. With more than 40 years painstaking eport they have conceived and used a wide variety of experimental screening systems, achieved successes. Finally they with one's own tests has keen verified that the crude drug being various kind of bioactive substance could inhibits tumor, increase immunity, wipe out free radical, prevent disease of cardiovascular system, have anti-radiation, anti-inflammeutory effects. At 1977 the Hippophae rhamnoides was written in Chinase Pharmacopoeia.