• 대한의생명과학회지
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• 제15권2호
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• pp.105-112
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• 2009

The screening of the anti-cancer activity of the chemical library provided 2-thio-4-aminopyrimidine as the initial hit. The confirmation of structure and biological effect of hit was performed by synthesis and biological evaluation. The optimization of hit was performed by derivatization of substituents while keeping the core structure. The evaluation of growth inhibitory activity was carried out using SRB assay against 6 human cancer cell lines and human fibroblast. The growth inhibitory activity of compounds showed substituent dependency and more than 5 compounds showed complete growth inhibition of cancer cell lines at 10 ${\mu}M$ concentration. Chemical library screening followed by synthetic modification provided possibility that 2-thio-4-aminopyrimidine can be used as a new scaffold for the development of anti-cancer agent.

• Journal of Microbiology and Biotechnology
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• 제16권12호
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• pp.1904-1911
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• 2006

The cell-free extracts of 250 yeasts were screened for their in vitro anti-angiogenic activity, to develop a new cancer metastasis inhibitor. Saccharomyces cerevisiae K-7 was selected as the producer of the anti-angiogenic agent, because it had the highest anti-angiogenic activity. The anti-angiogenic agent was produced maximally from hydrolysates of Saccharomyces cerevisiae K-7, when the yeast was cultured in yeast extract-peptone-dextrose medium at 30$^{\circ}C$ for 24 h, and cell-free extracts were than digested with pepsin for 4 h at 37$^{\circ}C$. The anti-angiogenic agent was further purified by ultrafiltration, Sephadex G-25 gel permeation chromatography and reverse-phase HPLC, and the anti-angiogenic activity of the final purified preparation was 72.7% at 10 $\mu$M/egg. The purified anti-angiogenic agent was found to originate from the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) molecule of Saccharomyces cerevisiae K-7, and its peptide sequence was Val-Ser-Trp-Tyr-Asp-Asn-Glu-Tyr-Gly-Tyr-Ser-Thr-Arg-Val-Val-Asp. In the MTT assay, the shape of the HT-l 080 cell was clearly changed to a circular type at 0.2 mM purified anti-angiogenic agent. This result indicated that the growth of the HT-I080 cell was significantly inhibited at 0.2 mM of the purified anti-angiogenic agent. The MMP activity of the treated HT-l080 cells was not affected, evidenced by the gelatin zymography, indicating that the anti-angiogenic mechanism of the purified anti-angiogenic agent is not mediated through MMP activity.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5855-5860
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• 2013

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- and time-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index (CI)<1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicity to normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment.

• BMB Reports
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• 제52권5호
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• pp.342-347
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• 2019

Methylation is a primary epigenetic mechanism regulating gene expression. 5-aza-2'-deoxycytidine is an FDA-approved drug prescribed for treatment of cancer by inhibiting DNA-Methyl-Transferase 1 (DNMT1). Results of this study suggest that prolonged treatment with 5-aza-2'-deoxycytidine could induce centrosome abnormalities in cancer cells and that CEP131, a centrosome protein, is regulated by DNMT1. Interestingly, cancer cell growth was attenuated in vitro and in vivo by inhibiting the expression of Cep131. Finally, Cep131-deficient cells were more sensitive to treatment with DNMT1 inhibitors. These findings suggest that Cep131 is a potential novel anti-cancer target. Agents that can inhibit this protein may be useful alone or in combination with DNMT1 inhibitors to treat cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6991-6996
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• 2015

In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.

• BMB Reports
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• 제56권7호
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• pp.410-415
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• 2023

Breast cancer has become the most common cancer among women worldwide. Among breast cancers, metastatic breast cancer is associated with the highest mortality rate. Twist1, one of the epithelial-mesenchymal transition-regulating transcription factors, is known to promote the intravasation of breast cancer cells into metastatic sites. Therefore, targeting Twist1 to develop anti-cancer drugs might be a valuable strategy. In this study, LY-290181 dose-dependently inhibited migration, invasion, and multicellular tumor spheroid invasion in breast cancer cell lines. These anti-cancer effects of LY-290181 were mediated through the down-regulation of Twist1 protein levels. LY-290181 inhibited extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways. Therefore, our findings suggest that LY-290181 may serve as a basis for future research and development of an anti-cancer agent targeting metastatic cancers.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.113-117
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• 2005

Organosulfur compounds have been shown to exert an anti-cancer activity. In an attempt to develop novel chemopreventive and anti-cancer agents for liver cancer, we synthesized allylthiopyridazine derivatives. We have previously shown that allylthiopyridazine derivatives exert inhibitory effects on proliferation, invasion and migration of SK-Hep-1 hepatocarcinoma cells in vitro. The in vivo anti-tumor effect of 3-methvl-6-allylthiopy-ridazine, named as K6, was also reported. In this study, we further investigated the preclinical anti-cancer efficacy of K6 for hepatocarcinoma using nude mice xenografted with Hep-G2 hepatocellular carcinoma cells. K6(20-100 mg/kg, orally administered everyday for 30 days) markedly decreased the tumor volume of Hep-G2 cell-transplanted nude mice as evidenced by ultrasonographic and plethysmogranhic analyses. The inhibitory effect on tumor volume was lower than that exerted by doxorubicin (2 mg/kg), intravenously injected) which was used as a positive control. This study shows that K6 efficiently suppresses xenograft tumor growth, revealing K6 as apotential anti-cancer agent for suppressing in vivo progression of liver cancer. Given that hepatocarcinoma is among the most prevalent and lethal malignancies and there is no effective treatment to date, our study may contribute to the potential drug development for liver cancer.

• International Journal of Oral Biology
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• 제40권2호
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• pp.85-91
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• 2015

Quercetin is a natural flavonoid phytochemical that is extracted from various plants. Having an advantages due to its varied biological properties, such as anti-inflammatory, anti-viral, anti-oxidant, and anti-cancer effects, quercetin is used to treat many diseases. Recently, it has been reported that autophagy inhibition may play a key role in anti-cancer therapy. Therefore, in this study, we investigated the molecular mechanisms and anti-cancer effects of quercetin in human osteosarcoma cells via autophagy inhibition. We ascertained that quercetin inhibited cell proliferation and induced cell death, these process is demonstrated that apoptosis via the mitochondrial pathway and the caspase cascade. Quercetin also induced autophagy which was inhibited by 3-MA, autophagy inhibitor and the blockade of autophagy promoted the quercetin-induced apoptosis, confirming that autophagy is a pro-survival process. Thus, these findings demonstrate that quercetin is an effective anti-cancer agent, and the combination of quercetin and an autophagy inhibitor should enhance the effect of anti-cancer therapy.

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.62-66
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• 2016

Amygdalin, D-mandelonitrile-${\beta}$-D-glucoside-6-${\beta}$-glucoside, belongs to aromatic cyanogenic glycoside group derived from rosaceous plant seed. Mounting evidence has supported the anti-cancer effects of amygdalin. However, whether amygdalin indeed acts as an anti-tumor agent against breast cancer cells is not clear. The present study aimed to investigate the effect of amygdalin on the proliferation of human breast cancer cells. Here, we show that amygdalin exerted cytotoxic activities on estrogen receptors (ER)-positive MCF7 cells, and MDA-MB-231 and Hs578T triple-negative breast cancer (TNBC) cells. Amygdalin induced apoptosis of Hs578T TNBC cells. Amygdalin downregulated B-cell lymphoma 2 (Bcl-2), upregulated Bcl-2-associated X protein (Bax), activated of caspase-3 and cleaved poly ADP-ribose polymerase (PARP). Amygdalin activated a pro-apoptotic signaling molecule p38 mitogen-activated protein kinases (p38 MAPK) in Hs578T cells. Treatment of amygdalin significantly inhibited the adhesion of Hs578T cells, in which integrin ${\alpha}5$ may be involved. Taken together, this study demonstrates that amygdalin induces apoptosis and inhibits adhesion of breast cancer cells. The results suggest a potential application of amygdalin as a chemopreventive agent to prevent or alleviate progression of breast cancer, especially TNBC.

• The Korean Journal of Physiology and Pharmacology
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• 제26권3호
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• pp.157-164
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• 2022

Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs in vivo, mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs in vitro and in vivo. DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.