• Journal of Applied Biological Chemistry
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• v.63 no.1
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• pp.103-110
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• 2020

Objective: The objective of our study was to investigate anti-cancer effects of Danggui Liuhuang Decoction extract bioconverted by protease liquid coenzyme of Aspergillus kawachii (DLD-BE), compared to a non-bioconverted DLD extract (DLD-E) and determine the underlying mechanisms. Methods: DLD-E and DLD-BE were evaluated for their ability to modulate these signaling pathways and suppress the proliferation of human colorectal cancer (CRC) cells, HCT-116, LoVo, and HT-29. The anti-cancer effects of DLD-E and DLD-BE were measured by using proliferation and migration assays, cell cycle analysis, Western blots, and real-time PCR. Results: In this study, treatment with DLD-E and DLD-BE at concentrations of 25-100 ㎍/mL inhibited proliferation and migration in human CRC cells. DLD-BE induced apoptotic cell death and decreased COX-2 expression in HT-29 cells. The mechanisms of action included modulation of the AKT and extracellular-signal-regulated kinase signaling cascades along with inhibition of COX-2 expression. The results demonstrate novel anti-cancer mechanisms of DLD-BE against the growth of human CRC cells. Thus, we propose that DLD-BE can be developed as a more potent supplement to inhibit colorectal tumor growth and intestinal inflammation than DLD-E.

• Journal of Applied Biological Chemistry
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• v.59 no.1
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• pp.31-36
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• 2016

Chlorine dioxide has been used for a disinfectant by exhibiting antimicrobial activity and is also potent to kill insect pests infesting stored grains. This study aimed to extend the usefulness of chlorine dioxide with respect to anticancer and antiviral activities. Cytotoxicity of chlorine dioxide was assessed against five different human cancer cell lines. Chlorine dioxide exhibited significant cytotoxicity against two breast cancer cell lines (MCF-7, MDA-MB-231) and three colorectal cancer cell lines (LoVo, HCT-116, SW-480). This cytotoxicity appeared to be associated with the capacity of chlorine dioxide to induce the production of reactive oxygen species (ROS). Compared to control insect cell lines, the cancer cell lines possessed much higher levels of ROS. On the other hand, a treatment of an antioxidant, vitamin E, significantly reduced the cytotoxicity, suggesting that the cytotoxicity was induced by high levels of ROS production. Chlorine dioxide exhibited antiviral activity against different viruses. A baculovirus, Autographa californica nuclear polyhedrosis virus (AcNPV), is a dsDNA insect virus and lost its viral activity to form polyhedral viral particles in response to chlorine dioxide. The antiviral activity against AcNPV was dependent on the incubation time with chlorine dioxide. Tobacco mosaic virus is a ssRNA plant virus and was reduced in its population after exposure to chlorine dioxide along with significant decrease of viral symptoms. These results indicate that chlorine dioxide possesses anticancer and antiviral activities probably due to its inducing activity of ROS production.

• Korean Journal of Plant Resources
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• v.29 no.3
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• pp.297-304
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• 2016

The seed of safflower (Carthamus tinctorius L) has been reported to suppress human cancer cell proliferation. However, the mechanisms by which safflower seed inhibits cancer cell proliferation have remained nuclear. In this study, the inhibitory effect of the safflower seed (SS) on the proliferation of human colorectal cancer cells and the potential mechanism of action were examined. SS inhibited markedly the proliferation of human colorectal cancer cells (HCT116, SW480, LoVo and HT-29). In addition, SS suppressed the proliferation of human breast cancer cells (MDA-MB-231 and MCF-7). SS treatment decreased cyclin D1 protein level in human colorectal cancer cells and breast cancer cells. But, SS-mediated downregulated mRNA level of cyclin D1 was not observed. Inhibition of proteasomal degradation by MG132 attenuated cyclin D1 downregulation by SS and the half-life of cyclin D1 was decreased in SS-treated cells. In addition, SS increased cyclin D1 phosphorylation at threonine-286 and a point mutation of threonine-286 to alanine attenuated SS-mediated cyclin D1 degradation. Inhibition of ERK1/2 by PD98059 suppressed cyclin D1 phosphorylation and downregulation of cyclin D1 by SS. In conclusion, SS has anti-proliferative activity by inducing cyclin D1 proteasomal degradation through ERK1/2-dependent threonine-286 phosphorylation of cyclin D1. These findings suggest that possibly its extract could be used for treating colorectal cancer.

• Journal of Dairy Science and Biotechnology
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• v.26 no.1
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• pp.5-10
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• 2008

This study was conducted to isolate protein components from culture supernatant of Lactobacillus casei. and measure anti-cancer activity. The protein components were isolated A and B on Ultrafiltration membrane(3, 10, 30, 100 KDa). And the protein components A and B were isolated fractions(number $3{\sim}9$) on FPLC. Experimental studies were progressed through the cell cytotoxicity and anti-cancer activities. Cell cytotoxicity test using human kidney normal cell(293) showed cytotoxicity of below 20% by the protein components A and B($100{\mu}g/mL$). The anti-cancer activity was increased up to 70% by the protein components A and B($100{\mu}g/mL$) in AGS(stomach cancer), A549(lung cancer), MCF-7 (breast cancer), SK-OV-3(ovary cancer) and LoVo(colon cancer). Cell cytotoxicity test was showed cytotoxicity of about 50% by the fractions(number 3, 8, 9) isolated FPLC. The others have not the cytotoxicity about the human normal cell. The anti-cancer activity was increased up to 70% by the fraction number 7 in cancer cell line. Therefore the components isolated from culture supernatant of Lactobacillus casei were showed anti-cancer activity.

• Journal of Korean Traditional Oncology
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• v.20 no.2
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• pp.5-11
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• 2015

Objective : The objective of this study was to investigate the anti-tumor activity of the complexed herbal formula, Haeamdan (HAD). Methods : Seven Cancer cell lines, LoVo, MCF-7, AGS, Sarcoma 180, HL-60, NCI-H69, LL/2, were prepared and the cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-2,5-dephenyl tetrazolium bromide (MTT) assay. HAD was applied with various concentrations from 0.1 to 1.0 mg/ml to figure out the appropriate dosage. ICR male mice were intraperitoneally implanted with Sarcoma 180 and divided into 8 species for each group. Control group was treated with normal saline, positive control group was treated with cyclophosphamide 8mg/kg, and experimental group was treated with HAD 1g/kg. Results : Among seven cancer cell lines, HAD exhibited strong cytotoxic activities to followed four cancer cell lines, that is, Sarcoma 180, HL-60, NCI-H69, and LL/2. These cytotoxic activity was expressed under 0.50 mg/ml of IC50 under 0.1~1mg/ml of OBW. When Sarcoma 180 cancer cell was implanted in ICR male mice and treated with the HAD, HAD prolonged the median overall survival for 3.6 days, from 17.5 to 21.1 days. Conclusion : HAD showed strong cytotoxicity to the cancer cells, Sarcoma 180, HL-60, NCI-H69, on in vitro study and it showed anti-tumor activity in vivo with the peritoneal cancer mice by prolonging the median survival for 3.6 days. Further researches would be expected to support the anti-tumor efficacy of HAD.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.402-409
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• 2016

It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.

• Journal of Korean Traditional Oncology
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• v.20 no.2
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• pp.13-21
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• 2015

Objective : The objective of this study was to investigate the experimental efficacy of anti-tumor activity of the complexed herbal formula, Onbaekwon (OBW), which was derived from the literature of Traditional Korean Medicine, Dongeuibogam. Methods : Nine Cancer cell lines, LoVo, MCF-7, HepG2, AGS, A549, NCI-H69, HL-60, Sarcoma 180, LL/2, were prepared and the cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-2,5-dephenyl tetrazolium bromide (MTT) assay. Four of them, NCI-H69, HL-60, Sarcoma 180, and LL/2, showed strong cytotoxic activities and they were additionally undergone flow cytometry to find out their effects on apoptosis. ICR male mice were implanted with Sarcoma 180 intraperitoneally and divided into 8 species for each group. Control group was treated with normal saline, positive control group was treated with cyclophosphamide 8mg/kg, and experimental group was treated with OBW 1 g/kg. Results : Among 9 cancer cell lines, NCI-H69, HL-60, Sarcoma 180, and LL/2, expressed less than 0.10 mg/ml of $IC_{50}$ under 0.1~1mg/ml of OBW. NCI-H69, HL-60, Sarcoma 180, and LL/2, showed dose-dependent efficacy of apoptosis. When Sarcoma 180 cancer cell was implanted in ICR male mice and treated with the OBW, they prolonged the median overall survival for 0.8 days, from 17.5 to 18.3. Conclusion : OBW showed strong cytotoxicity to some cancer cells, which are NCI-H69, HL-60, Sarcoma 180, and LL/2, and its apoptotic activity was dose-dependent. OBW prolonged the median survival of mice implanted with Sarcoma 180. Further researches would be expected to support the efficacy of OBW.