• 대한의생명과학회지
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• 제19권2호
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• pp.98-104
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• 2013

Radiation is one of the major therapy for the removal of cancer cells. The results of the radiation therapy depend on the radio-resistance of cancer cells. For the effective treatment in these radio-resistant cancers, the use of chemicals that act on cancer cells is known to enhance the cytotoxic effects of radiation therapy. In this study, I investigated the effect of potassium cyanate (KCN) on the irradiated-colorectal cancer cell line, HCT 116 cells. KCN induces the carbamylation of proteins and can change the biological activity of various human cells. To understand the effect of KCN on the radiosensitivity of HCT 116 cells, I examined alteration of the cell cycle, generation of reactive oxygen species (ROS), cell viability, apoptosis and intracellular signaling proteins in the irradiated cells with/without KCN treatment. Combination treatment caused significant increase in sub $G_0/G_1$ and ROS generation in HCT 116 cells. KCN inhibited the proliferation and cell viability in irradiated HCT 116 cells. KCN-induced apoptosis of irradiated cells was processed via the activation of caspase 3 and caspase 9. Apoptosis-associated signal proteins, including Bax and Bcl-2 were regulated by irradiation with KCN treatment. Taken together, these results may indicate that KCN enhances the radiosensitivity of radio-resistant cell and then has a synergistic effect on radiation therapy in colorectal cancer.

• 대한의생명과학회지
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• 제17권3호
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• pp.177-184
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• 2011

Potassium cyanate (KOCN) is an inorganic compound and induces the carbamylation of proteins with cytotoxic effects on human cells. Although there is a potential cytotoxic molecule, the role of KOCN on the apoptosis of cancer cell is not well understood. The present study investigated the effects of KOCN on the human colorectal cancer cell line, HCT 116 cells. To understand the anti-cancer effect of KOCN on HCT 116 cells, we examined alteration of apoptosis, the intracellular $Ca^{2+}$ concentration, the intracellular signaling pathway and generation of reactive oxygen species (ROS) in these cells treated with KOCN. The apoptosis of HCT 116 cells was induced by KOCN in a dose-dependent manner at 24 hours and 48 hours, respectively. The apoptosis was processed via the cleavage of poly ADP-ribose polymerase (PARP) and activation of caspase 3 in HCT 116 cells. KOCN induced the elevation of intracellular $Ca^{2+}$ concentration and changed the expressions of Bcl-2 family proteins. The pro-apoptotic Bax was continuously up-regulated, and the anti-apoptotic Bcl-2 was down-regulated by KOCN. KOCN also induced the hyperpolarization of mitochondria and the generation of ROS in HCT 116 cells. Taken together, these results indicate that KOCN induces the apoptosis of HCT 116 cells by disruption of $Ca^{2+}$ homeostasis and via mitochondrial pathway. This study provides the compound that may be used as a potent agent for the treatment of colorectal cancer.

• 대한의생명과학회지
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• 제20권1호
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• pp.32-38
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• 2014

Potassium cyanate (KOCN) that is known as an inducer of the protein carbamylation is an inorganic compound and is the conjugate based of cyanic acid (HOCN). Based on these studies, we confirmed that KOCN induces the apoptosis of the human colorectal cancer cell line, HCT 116 cells, by various mitochondrial pathways. To investigate other mechanisms of KOCN-mediated apoptosis, in the present study, we examined KOCN-induced cytokines production in HCT 116 cells and identified the intracellular signaling pathway in these processes. We first demonstrated that KOCN considerably increased the cell apoptosis via intracellular $Ca^{2+}$ signaling, mitochondrial dysfunction and ROS production. And then we examined TNF-${\alpha}$ and IL-$1{\beta}$ levels mediated by KOCN in HCT 116 cells. Although IL-$1{\beta}$ was not involved in KOCN-mediated HCT 116 cell apoptosis, the release of TNF-${\alpha}$ was mediated by KOCN in HCT 116 cells via NF-${\kappa}B$ activation. Apoptosis was also enhanced by incubation with supernatants from HCT 116 cells after KOCN treatment and this effect was partially reduced by BAY 11-7085 pre-treated supernatant. Taken together, our results indicate that KOCN-induced apoptosis in HCT 116 cells is dependent on the releases of TNF-${\alpha}$ and the increased factors and that the mechanism involves the activation of NF-${\kappa}B$.

• 한국방사선학회논문지
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• 제13권1호
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• pp.125-132
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• 2019

Potassium cyanate는 무기화합물로 단백질의 번역 후 과정에서 카바밀화(carbamylation)을 유도할 수 있고 이러한 카바밀화 반응은 다양한 질병 및 조건에서 세포의 사멸과 관련이 있다. 이전 연구결과에서 KCN은 사람 대장암 세포주인 HCT 116세포의 방사선 감수성을 향상시키는 것을 확인하였지만 그 기전을 명확히 규명하기에는 많이 부족한 실정이다. 본 연구에서는 방사선에 다소 저항성을 가지는 대장암 세포에서 KCN이 방사선 감수성을 향상시키고 세포사멸 시키는 기전을 확인하기 위해 2 mM의 KCN 처리 후 저 선량의 광자선을 조사하여 세포주기, 세포 생존율, 세포 사멸 관련 단백질(caspase-1, PARP) 발현량, $TNF-{\alpha}$ 분비 및 $TNF-{\alpha}$ 관련 전사인자($NF-{\kappa}B$)의 연관성을 확인하였다. 그 결과 KCN 처리 후 광자선을 조사한 세포에서 caspase-3 및 PARP의 활성이 증가하고 이는 세포주기의 정지와 세포사멸을 유도하였다. 또한 이 과정에서 DNA 전사인자인 $NF-{\kappa}B$에 의해 세포 외로 $TNF-{\alpha}$를 지속적으로 분비하여 세포사멸에 관여함을 확인하였다. 이러한 결과들을 토대로 KCN이 radiosensitizer로서 작용할 수 있는 가능성이 있다고 사료된다.

• 한국식품과학회지
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• 제25권5호
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• pp.565-570
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• 1993

가공 과정 중 갈변에 관여하는 돼지감자의 peroxidase가 ammonium sulfate, DEAE-cellulose column, Sephacryl S-200 column chromatography에 의하여 36.65배로 정제되었다. 이 효소는 p-phenylenediamine을 기질로 사용하였을 때 pH5.0가 활성 최적 pH이었으며 pH $5.0{\sim}6.0$의 범위에서 비교적 안정하였다. 열 불활성화 곡선은 1차 곡선에서 벗어났고 60, 70, $80^{\circ}C$에서의 D값은 각각 86, 45, 33초이었으며 활성화에너지는 4,111 J/mole이었다. 이 효소의 기질특이성은 amine류 중에서 p-phenylenediamine과 가장 친화력이 좋았고 potassium cyanate, sodium diethyldithiocarbamate, L-ascorbic acid, sodium hydrosulfite, L-cysteine에 의해 활성이 완전히 억제되었으며 $Ca^{2+},\;Cu^{2+}$에 의해서는 활성이 촉진되었다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.73-73
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• 1997

A series of 4-phenyl-1-(indoline-5-sulfonyl)-2-imidazolone derivatives has been synthesized starting from 2-bromoacetophenone. Reaction of 2-aminoacetophenone obtained from 2-bromoacetophenon by Delepin synthesis and potassium cyanate affords 1,3-dihydro-4-phenyl-2-imidazolone. This key intermediate was treated with sodium hydride and N-trifluoroacetyl-indoline-5-sulfonylchloride, and trifluoroacetyl group was deprotected to give 4-Phenyl-1-(indoline-5-sulfonyl)-2-imidazolone. Various substituents were introduced on the nitrogen of indoline. Antitumor activity of this series of compound was evaluated by MTT method. Nearly all of the compounds showed broad-spectrum activity.

• 대한의생명과학회지
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• 제20권2호
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• pp.96-102
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• 2014

Staphylococcal enterotoxin B (SEB) is bacterial toxin that induces the activation of immune cells. Because the inhibition of pro-inflammatory effect of SEB can resolve the inflammation, I determined the influence of functional or structural change of SEB on immune cells. The post translational modification of protein occurs through carbamylation. Carbamylation can change the structure of proteins and can modify the biological activity of protein. In the present study, I investigated the effect of carbamylated SEB (CSEB) on the inflammatory response mediated by LPS in HL-60 cells. To determine the anti-inflammatory effect of CSEB, I produced carbamylated SEB using potassium cyanate (KCN) and then examined whether CSEB involved in cytokine releases and apoptosis of LPS-stimulated HL-60 cells. Although CSEB had not any effect on the LPS-stimulated HL-60 cells, the protein levels of IL-8, TNF-${\alpha}$ and IL-$1{\beta}$ were significantly decreased by CSEB without cytotoxicity. CSEB also blocked Akt and NF-${\kappa}B$ activation. These results indicate that the suppressive effect of CSEB in LPS-stimulated cytokine releases is occurred by inhibition of Akt and NF-${\kappa}B$ activity. Through further studies, CSEB may be used as anti-inflammatory molecule that makes the immune system more efficient.