• Korean Journal of Acupuncture
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• v.29 no.2
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• pp.271-289
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• 2012

Objectives : Ganoderma lucidum(Ganoderma or lingzhi, 靈芝) is a well-known oriental medical mushroom containing many bioactive compounds. The possible mechanisms involved in its effects on cancer cells remain to be elucidated. In the present study, the anti-proliferative and apoptotic activities of the G. lucidum ethanol extract(GEE), in AGS human gastric cancer cells were investigated. Methods : It was found that exposure of AGS cells to GEE resulted in the growth inhibition in a dose and time dependent manner as measured by trypan blue count and MTT assay. The anti-proliferative effect of GEE treatment in AGS cells was associated with morphological changes and formation of apoptotic bodies, and the flow cytometry analysis confirmed that GEE treatment increased the populations of apoptotic-sub G1 phase. Growth inhibition and apoptosis of AGS cells by GEE were connected with a concentration and time-dependent up-regulation of tumour necrosis factor-related apoptosis-inducing ligand(TRAIL) expression. Results : The levels of XIAP and survivin expression, members of IAP family proteins, were gradually down-regulated by GEE treatment. However other members of IAP family proteins such as cIAP-1 and cIAP-2 remained unchanged in GEE-treated AGS cells. GEE treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9 and a concomitant degradation of poly(ADP-ribose) polymerase(PARP) protein, a caspase-3 substrate protein. Additionally, GEE-induced apoptosis was associated with the inhibition of Akt activation in a concentration and time-dependent manner, and pre-treatment with LY294002, a phosphoinositide 3-kinase(PI3K)/Akt inhibitor, significantly increased GEE-induced growth inhibition and apoptosis. Conclusions : Therefore, G. lucidum has a strong potential as a therapeutic agent for preventing cancers such as gastric cancer cells.

• Archives of Pharmacal Research
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• v.27 no.4
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• pp.429-435
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• 2004

Ginseng has an anti-cancer effect in several cancer models. This study was to characterize active constituents of ginseng and their effects on proliferation of prostate cancer cell lines, LNCaP and PC3. Cell proliferation was measured by $[^3H]$thymidine incorporation, the intracellular calcium concentration by a dual-wavelength spectrophotometer system, effects on mite-gen-activated protein (MAP) kinases by Western blotting, and cell attachment and morphologic changes were observed under a microscope. Among 11 ginsenosides tested, ginsenosides $Rg_3\;and\;Rh_2$ inhibited the proliferation of prostate cancer cells. $EC_{50}s\;of\;Rg_3\;and\;Rh_2$ on PC3 cells were $8.4{\mu}M\;and\;5.5{\mu}M$, respectively, and $14.1{\mu}M\;and\;4.4{\mu}M$ on LNCaP cells, respectively. Both ginsenosides induced cell detachment and modulated three modules of MAP kinases activities differently in LNCaP and PC3 cells. These results suggest that ginsenosides $Rg_3\;and\;Rh_2$-induced cell detachment and inhibition of the proliferation of prostate cancer cells may be associated with modulation of three modules of MAP kinases.

• The Journal of Internal Korean Medicine
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• v.43 no.4
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• pp.529-541
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• 2022

Objectives: Acanthopanax senticosus is a tree used in traditional medicine for various diseases. In this study, we investigated the anti-cancer effects of a water extract of Acanthopanax senticocus fruit (ASF) on 2 human breast cancer cell lines (MCF-7 and MDA-MB-231). Methods: The MTT assay was used to assess cell proliferation. The expression of apoptosis-related genes was assessed by quantitative real-time PCR. Results: ASF treatment caused a dose-dependent inhibition of cell growth in both estrogen-independent MDA-MB-231 and estrogen-dependent MCF-7 breast cancer cells. ASF decreased mRNA expression of the apoptotic suppressor gene Bcl-xL, and increased mRNA expression of proapoptotic genes. ASF increased the mRNA expression of p21 and RIP-1 in both cell types. ASF decreased the mRNA expression of survivin in the MCF-7 cell line. Conclusions: ASF exhibits anti-cancer activity involving apoptotic cell death.

• BMB Reports
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• v.53 no.10
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• pp.533-538
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• 2020

Notch signaling has been identified as a critical pathway in gastric cancer (GC) progression and metastasis, and inhibition of Delta-like ligand 4 (DLL4), a Notch ligand, is suggested as a potent therapeutic approach for GC. Expression of both DLL4 and vascular endothelial growth factor receptor 2 (VEGFR2) was similar in the malignant tissues of GC patients. We focused on vascular endothelial growth factor (VEGF), a known angiogenesis regulator and activator of DLL4. Here, we used ABL001, a DLL4/VEGF bispecific therapeutic antibody, and investigated its therapeutic effect in GC. Treatment with human DLL4 therapeutic antibody (anti-hDLL4) or ABL001 slightly reduced GC cell growth in monolayer culture; however, they significantly inhibited cell growth in 3D-culture, suggesting a reduction in the cancer stem cell population. Treatment with anti-hDLL4 or ABL001 also decreased GC cell migration and invasion. Moreover, the combined treatment of irinotecan with anti-hDLL4 or ABL001 showed synergistic antitumor activity. Both combination treatments further reduced cell growth in 3D-culture as well as cell invasion. Interestingly, the combination treatment of ABL001 with irinotecan synergistically reduced the GC burden in both xenograft and orthotopic mouse models. Collectively, DLL4 inhibition significantly decreased cell motility and stem-like phenotype and the combination treatment of DLL4/VEGF bispecific therapeutic antibody with irinotecan synergistically reduced the GC burden in mouse models. Our data suggest that ABL001 potentially represents a potent agent in GC therapy. Further biochemical and pre-clinical studies are needed for its application in the clinic.

• The Journal of Internal Korean Medicine
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• v.29 no.1
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• pp.130-148
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• 2008

Objective : This study was designed to investigate the effect of the water extract of Gamisamgibopae-tang(GMSGBPT), an oriental herbal formulation, on the growth of NCI-H460 and A549 human non-small-cell lung cancer cell lines. Methods : Cytotoxicity and cell morphology were evaluated by MTT assay and inverted microscope, respectively. Apoptosis was detected using agarose gel electrophoresis and flow cytometer. The expression levels of mRNAs and proteins of target genes were determined by RT-PCR and western blot analyses, respectively Result and Conclusion : We found that exposure of A549 cells to GMSGBPT resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay, but GMSGBPTdid not affect the growth of NCI-H460 cells. The anti-proliferative effect of GMSGBPT treatment in A549 cells was associated with morphological changes, formation of apoptotic bodies and DNA fragmentation, and flow cytometry analysis confirmed that GMSGBPT treatment increased the populations of apoptotic-sub G1 phase. Growth inhibition and apoptotic cell death by GMSGBPT were connected with a up-regulation of cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) mRNA and protein in a tumor suppressor p53-independent fashion. However GMSGBPT treatment did not affect other growth regulation-related genes such as early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1), inducible nitric oxide synthase (iNOS), cyclooxygenases (COXs), telomere-regulatory factors in A549 orNCI-H460 cells. Taken together, these findings partially provide novel insights into the possible molecular mechanism of the anti-cancer activity of GMSGBPT.

• Radiation Oncology Journal
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• v.33 no.4
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• pp.328-336
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• 2015

Purpose: Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. Materials and Methods: Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). Results: This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. Conclusion: These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.

• Journal of Microbiology and Biotechnology
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• v.29 no.8
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• pp.1212-1220
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• 2019

The study of metabolomics in natural products using the diverse analytical instruments including GC-MS, LC-MS, and NMR is useful for the exploration of physiological and biological effects and the investigation of drug discovery and health functional foods. Cordyceps militaris has been very attractive to natural medicine as a traditional Chinese medicine, due to its various bioactive properties including anti-cancer and anti-oxidant effects. In this study, we analyzed the metabolite profile in 50% ethanol extracts of C. militaris fruit bodies from three development periods (growth period, matured period, and aging period) using $^1H-NMR$, and identified 44 metabolites, which are classified as 16 amino acids, 10 organic acids, 5 carbohydrates, 3 nucleotide derivatives, and 10 other compounds. Among the three development periods of the C. militaris fruit body, the aging period showed significantly higher levels of metabolites including cordycepin, mannitol (cordycepic acid), and ${\beta}-glucan$. Interestingly, these bioactive metabolites are positively correlated with antitumor growth effect; the extract of the aging period showed significant inhibition of HepG2 hepatic cancer cell proliferation. These results showed that the aging period during the development of C. militaris fruit bodies was more highly enriched with bioactive metabolites that are associated with cancer cell growth inhibition.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2939-2946
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• 2015

Many of the anti-cancer agents currently used have an origin in natural sources including plants. Aloe vera is one such plant being studied extensively for its diverse health benefits, including cancer prevention. In this study, the cytotoxic potential of Aloe vera crude extract (ACE) alone or in combination with cisplatin in human breast (MCF-7) and cervical (HeLa) cancer cells was studied by cell viability assay, nuclear morphological examination and cell cycle analysis. Effects were correlated with modulation of expression of genes involved in cell cycle regulation, apoptosis and drug metabolism by RT-PCR. Exposure of cells to ACE resulted in considerable loss of cell viability in a dose- and time-dependent fashion, which was found to be mediated by through the apoptotic pathway as evidenced by changes in the nuclear morphology and the distribution of cells in the different phases of the cell cycle. Interestingly, ACE did not have any significant cytotoxicity towards normal cells, thus placing it in the category of safe chemopreventive agent. Further, the effects were correlated with the downregulation of cyclin D1, CYP 1A1, CYP 1A2 and increased expression of bax and p21 in MCF-7 and HeLa cells. In addition, low dose combination of ACE and cisplatin showed a combination index less than 1, indicating synergistic growth inhibition compared to the agents applied individually. In conclusion, these results signify that Aloe vera may be an effective anti-neoplastic agent to inhibit cancer cell growth and increase the therapeutic efficacy of conventional drugs like cispolatin. Thus promoting the development of plant-derived therapeutic agents appears warranted for novel cancer treatment strategies.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.553-560
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• 2004

In the present study, we investigated the anti-proliferative effects of aqueous extract of Wikyung-tang(WKT) on the growth of human lung carcinoma cell line A549. WKT treatment declined the cell viability and proliferation of A549 cells in a concentration-dependent manner. The anti-proliferative effects by WKT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. WKT treatment induced an inhibition and/or degradation of apoptotic target proteins such poly(ADP-ribose) polymerase (PARP) and phospholipase C-γ1 (PLC-γ1). WKT treatment did not affect the levels of other Bcl-2 family gene products, such as Bcl-2, Bax and Bad. Western blot analysis and RT-PCT data revealed that the levels of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 were induced by WKT treatment in A549 cells. Additionally, WKT treatment induced the down-regulation of telomerase reverse transcriptase mRNA (hTERT) expression of A549 cells, however, the levels of other telomere-regulatory gene products were not affected. Taken together, these findings suggest that WKT-induced inhibition of human lung cancer cell proliferation is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products and WKT may have therapeutic potential in human lung cancer.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.185-189
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• 2005

We isolated a coumarin compound, isoimperatorin ($C_{16}H_{14}O_4$ mw: 270) from Angelica koreana through silica gel column chromatography, and characterized it by NMR. Here, for the first time we observed that isoimperatorin (25, 50 and 100 ${\mu}M$) treatment for 24-72h inhibited growth and induced death in human prostate carcinoma DU145 cells. Further, in mechanistic investigation, isoimperatorin-induced cell growth inhibition was associated with a strong increase in G1 arrest in cell cycle progression, which started at 24h of the treatment. These findings suggest a novel anticancer efficacy of isoimperatorin mediated via induction of G1 arrest against hormone refractory human prostate carcinoma DU145 cells.