소목 추출물의 구강암 및 골육종 세포주에 대한 항암작용에 관한 연구

이종수,김여갑,김정희 大韓口腔外科學會 2003 大韓口腔外科學會誌 Vol.27 No.4

귀비탕(歸脾湯)이 비소세포 폐암세포(NCI-H520) 이식 마우스에서 항암 및 면역 활성에 미치는 영향

손지영,최해윤,김종대,Son, Ji-Young,Choi, Hae-Yun,Kim, Jong-Dae 대한한방내과학회 2012 大韓韓方內科學會誌 Vol.33 No.4

Objectives : This study was to observe anticancer and related immunomodulatory effects of Kwibi-tang extracts (KBTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Methods : Three different dosages of KBTe, 50, 100 and 200 mg/kg were orally administered once a day for 42 days from 11 days after tumor cell inoculation. Six groups, each of 8 mice per group were used in the present study. Changes in body weight, tumor volume and weight, lymphatic organs (spleen and popliteal lymph node), serum interferon (IFN)-${\gamma}$ levels, splenocytes NK cell activity and peritoneal macrophage activities, splenic tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-10 contents were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. The results were compared with a potent cytotoxic anticancer agent, 5-FU (5-Fluorouracil) 30 mg/kg, intraperitoneal treatment (3-day intervals for 42 days, the optimal effective treatment regimes already confirmed). Results & Conclusions : This study suggest that over 50 mg/kg of KBTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory effects. Although relatively lower anticancer effects were observed in KBTe 200 mg/kg treated mice as compared with 5-FU 30 mg/kg treated mice, no meaningful favorable immunomodulatory effects were observed after 5-FU treatment in the present study.

소목 추출물의 구강암 및 골육종 세포주에 대한 항암작용에 관한 연구

이종수,김여갑,김정희,Lee, Jong-Su,Kim, Yeo-Gab,Kim, Jeong-Hee 대한구강악안면외과학회 2001 대한구강악안면외과학회지 Vol.27 No.4

Anticancer effect of methanol extract of Caesalpinia sappan L. on oral carcinoma (KB) and osteosarcoma (HOS) cells were investigated in this study. In order to elucidate the anticancer mechanism of Caesalpinia sappan L, we analyzed telomerase inhibitory effect of the methanol extract of Caesalpinia sappan L. In addition we prepared 5 fraction samples according to its polarity differences and analyzed anticancer effects on oral carcinoma and osteosarcoma cells. Following results are obtained in this study. 1. 50% cell proliferation inhibitory value ($IC_{50}$) of the methanol extract of Caesalpinia sappan L. against oral carcinoma (KB) cells and osteosarcoma (HOS) cells were $9.0{\mu}g/ml$ and $10.9{\mu}g/ml$, respectively. 2. The methanol extract of Caesalpinia sappan L. showed inhibitory effect of telomerase which is required for cancer cell immortality. Therefore, it seems that the anticancer effect of methanol extract of Caesalpinia sappan is at least partially due to telomerase inhibitory effect. 3. Five fraction samples were prepared according to its polarity and 88.7% of ingredient of total methanol extract was transferred to ethylacetate fraction. Thin layer chromatography analysis showed that dichloromethane fraction contained ingredient with relatively high polarity and ethylacetate fraction contained similar ingredient found in total methanol extract. 4. Anticancer effect was observed in n-hexane, dichloromethane, and ethylacetate fractions. The highest anticancer effect was found in dichloromethane fraction which had $IC_{50}$ value of 4.4 and $>4.0{\mu}g/ml$ against oral carcinoma (KB) cells and osteosarcoma (HOS) cells, respectively.

플라보노이드의 항암 효능과 면역중재성 항암 작용 및 기작

이제형,이용규 한국식품영양과학회 2019 한국식품영양과학회지 Vol.48 No.8

The side effects resulting from chemotherapy for cancer treatment are mostly related to immunosuppression or reduced immunity. To prevent such side effects, many studies have started focusing on natural dietary substances that have immunomodulatory effects. Flavonoids have been a particular focus of such research because they are known, for over 20 years, to have outstanding antioxidant and anti-inflammatory effects. New molecular targets of anticancer activities continue to be discovered and a comprehensive overview of various anticancer immunity studies is soon expected, and so this current study reviews the recent study results on flavonoids (quercetin, hesperidin, epigallocatechin, genistein, luteolin, kaempferol, apigenin), their anticancer activities, their anticancer immunity, their anti-inflammatory cancer suppression activity, and the mechanism of these actions. In particular, immunomodulatory flavonoids activate effector cells like macrophages, NK cells, and neutrophil granulocytes, and these cells then infiltrate themselves into tumor to slay these malignant cancer cells. Immunomodulatory flavonoids also suppress the formation and growth of tumor by suppressing TR cells, activating TC and TH cells, increasing IFN-γ, and decreasing PD-L1, IL-1 and TLR. Fortunately, there were some recent clinical reports on flavonoids preventing cancer recurrence. However, the number of reports is not enough to support flavonoids’ clinical effects and adoption as a standard treatment, because their bioavailability is low. Despite the low bioavailability, flavonoids are highly effective and safe, and each flavonoid has different molecular targets in a cell. That is why more in-depth studies are needed to find the results of combined treatment of various flavonoids or flavonoids treatment combined with other pharmaceutical substances. 암 치료 시 화학요법제로 인한 부작용의 대부분은 면역 억제 또는 면역력 저하와 관련되어 있다. 이러한 부작용을 방지하기 위하여 면역중재성 식이 천연물에 많은 관심이 집중되고 있다. 플라보노이드는 2000년도 이전부터 항산화 작용과 항염증 작용이 뛰어난 물질로 알려져 오면서 이 물질의 항암 효능에 관하여 여러 연구들이 이루어졌다. 항암 작용의 연구를 위한 여러 분자 타깃이 새로이 발견되고 면역중재성 항암 작용에 대한 포괄적인 분석이 요구됨에 따라서 본 연구는 최근에 보고된 결과를 중심으로 플라보노이드(퀘르세틴, 헤스페리딘, 에피갈로카테친, 제니스타인, 루테올린, 켐페롤, 아피게닌)의 항암 효능, 면역중재성 항암 작용, 항염증성 종양 억제 작용과 그의 작용 기전을 확인하였다. 특히 면역중재성 플라보노이드는 종양에 대항하기 위하여 마크로파지, NK 세포, 호중구와 같은 효과 세포(effector cell)를 활성화시켜 이를 종양에 침투시키고 대항할 뿐 아니라, TR 세포 억제, TC와 TH 세포 활성화, IFN-γ 증가, PD-L1 감소, IL-1 감소 및 TLR 감소를 통하여 종양 생성 및 증식을 억제하는 것으로 보고되고 있다. 이러한 플라보노이드의 탁월한 효능과 함께 최근에는 암의 재발을 억제한다는 임상적 사례도 보고되고 있지만, 임상적 효능과 적용에 관한 사례는 부족하다. 이는 플라보노이드의 생체이용률이 약하기 때문으로 알려졌는데, 이러한 문제점들을 극복하기 위하여 플라보노이드 구조의 활성기 보존 및 임상적 적용에 대한 여러 연구도 진행되고 있다. 플라보노이드는 생체이용률은 낮지만, 효능과 안전성이 뛰어나며 각각의 플라보노이드는 세포 내의 작용점이 다르다는 장점을 고려할 때 여러 플라보노이드와의 병용 또는 다른 치료 약물과의 병용으로 나타나는 반응 또는 상승 효능에 대해 많은 연구 결과가 요구된다.

마우스 T 세포 림프종 EL4 세포에 대한 metformin 단독 및 2-deoxy-D-glucose와 병용의 항암효과

Si-Yeon Kim,주홍구 대한수의학회 2023 大韓獸醫學會誌 Vol.63 No.3

Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.

인삼양영탕(人蔘養榮湯)이 비소세포 폐암세포(NCI-H520) 이식 마우스에서 항암 및 면역 활성에 미치는 영향

송광규,곽민아,김종대,Song, Kwang-Kyu,Kwak, Min-A,Kim, Jong-Dae 대한한의학방제학회 2013 大韓韓醫學方劑學會誌 Vol.21 No.1

Objectives : The object of this study was to observe anticancer and related immunomodulatory effects of Insamyangyoung-tang extracts (ISYYTe) on non-small cell lung carcinoma (squamous epithelial carcinoma), NCI-H520, xenograft Balb/c nu-nu nude mice. Methods : Three different dosages of ISYYTe, 50, 100 and 200 mg/kg were orally administered once a day for 42 days from 11 days after tumor cell inoculation. Six groups, which are intact control, tumor bearing control, 5-fluorouracil (FU) 30 mg/kg, ISYYTe 50 mg/kg, ISYYTe 100 mg/kg, ISYYTe 200 mg/kg, each of 8 mice per group were used in the present study. Changes on the body weight, tumor volume and weight, lymphatic organ (spleen and popliteal lymph node), serum interferon (IFN)-${\gamma}$ levels, splenocytes NK cell activity and peritoneal macrophage activities, splenic tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-10 contents were observed with tumor mass and lymphatic organ histopathology to detect anticancer and immunomodulatory effects. Results : As results of ISYYTe 50, 100 and 200 mg/kg treatment, decreases in the tumor volumes and weights were detected. At histopathological observations, decreases of tumor cell volumes in tumor masses were dose-dependently decreased mediated by increases of apoptosis among tumor cells by treatment of all three different dosages of ISYYTe. As results of tumor cell inoculation, marked decreases of spleen and popliteal lymph node weights, serum IFN-${\gamma}$, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents and splenocytes were observed with histopathological atrophic changes of spleen and popliteal lymph nodes. Conclusions : Over 50 mg/kg of ISYYTe showed favorable anticancer effects on the NCI-H520 cell xenograft with immunomodulatory effects. Although relatively lower anticancer effects were observed in ISYYTe 200 mg/kg treated mice as compared with 5-FU 30 mg/kg treated mice, there are no meaningful favorable immunomodulatory effects were observed after 5-FU treatment in the present study.

백혈병 세포주에 대한(±)-ar-Turmerone, 자근 및 황금추출물에 의한 항암제의 세포독성 증강효과

이윤영,유관희,김삼용,안병준 忠南大學校 癌共同硏究所 1991 癌共同硏究所 硏究誌 Vol.1991 No.-

백혈병 세포중 대한(±)-ar-Turmerone, 자근 및 황금추출물에 의한 항암제의 세포독성 증강효과

이윤영,유관희,김삼용,안병준 충남대학교 암연구소 1991 癌共同硏究所 硏究誌 Vol.1 No.1

Using the colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT)assay, we evaluated the chemosensitivity of 8 anticancer drugs{vincristine(VCR), vinblastine (VBL), adriamycin(ADR), cisplatin(CPDD), etoposide(VP-16), cytosine arabinoside(ara-C), bleomycin (Bleo) and cyclophosphamide(CYC)} and the cytotoxicity-enhancing effects of (±)-ar-turmerone and the extracts of the crude drugs {Lithospermum erythrorhizon(LE) and Scutellaria baicalensis (SB)} on the above mentioned anticancer drugs against HL-60 and KG-1 cells among 8 anticancer drugs, VCR, VBL, ADR, and CPDD inhibited the growth of both cell lines by more than 50%, while VP-16, ara-C, Bleo, and CYC were less effective. (±)-ar-Turmerone had significant inhibitory effects against both cell lines, showing the ID_(50) values of 11.730 μg/ml and 0.292 μg/ml for HL-60 and KG-1 cells, respectively. But the extracts of LE and SB roots showed no significant cytotoxic effects. According to ID_(50) values, the cytotoxicities of VCR, VBL and ADR against HL-60 were enhanced two, eight and three times by mixing (±)-ar-turmerone, five, seven and three times by adding the extract of LE root, and twenty, six and three times by mixing the extract of SB root, respectively. The cytotoxicities of the above mentioned drugs against KG-1 cell were enhanced two, seven and three times by mixing (±)-ar-turmerone, two, three and three times by combining wilth the extract of LB root, and two, five and two times by adding the extract of SB root, respectively. The cytotoxicity-potentiating effects of (±)-ar-turmerone and the extracts of LE and SB roots against HL-60 cell were greater than KG-1 cell.

백혈병 세포주에 대한(±)-ar-Turmerone, 자근 및 황금추출물에 의한 항암제의 세포독성 증강효과

이윤영,유관희,김삼용,안병준 충남대학교 약학대학 의약품개발연구소 1991 藥學論文集 Vol.7 No.-

Using the colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay, we evaluated the chemosensitivity of 8 anticancer drugs{vincristine(VCR), vinblastine(VBL), adriamycin(ADR), cisplatin(CPDD), etoposide(VP-16), cytosine arabinoside(ara-C), bleomycin(Bleo) and cyclophosphamide(CYC)} and the cytotoxicity-enhancing effects of (±)-ar-turmerone and the extracts of the crude drugs {Lithospermum erythrorhizon(LE) and Scutellaria baicalensis (SB)} on the above mentioned anticancer drugs against HL-60 and KG-1 cells among 8 anticancer drugs, VCR, VBL, ADR, and CPDD inhibited the growth of both cell lines by more than 50%, while VP-16, ara-C, Bleo, and CYC were less effective. (±)-ar-Turmerone had significant inhibitory effects against both cell lines, showing the ID_50 values of 11.730 ㎍/㎖ and 0.292 ㎍/㎖ for HL-60 and KG-1 cells. respectively. But the extracts of LE and SB roots showed no significant cytotoxic effects. According to ID_50 values, the cytotoxicities of VCR, VBL and ADR against HL-60 were enhanced two, eight and three times by mixing (±)-ar-turmerone, five, seven and three times by adding the extract of LE root, and twenty, six and three times by mixing the extract of SB root, respectively. The cytotoxicities of the above mentioned drugs against KG-1 cell were enhanced two, seven and three times by mixing (±)-ar-turmerone, two, three and three times by combining with the extract of LB root, and two, five and two times by adding the extract of SB root, respectively. The cytotoxicity-potentiating effects of (±)-ar-turmerone and the extracts of LE and SB roots againg HL-60 cell were greater than KG-1 cell.

백혈병 세포주에 대한 (±)-ar-Turmerone, 자근 및 황금추출물에 의한 항암제의 세포독성 증강효과

이윤영,유관희,김삼용,안병준 충남대학교부설 생명공학연구소 1992 생물공학연구지 Vol.2 No.-

Using the colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide](MTT)assay, we evaluated the chemosensitivity of 8 anticancer drugs{vincristine(VCR), vinblastine(VBL), adriamycin(ADR), cisplatin(CPDD), etoposide(VP-16), cytosine arabinoside(ara-C), bleomycin(Bleo) and cyclophosphamide(CYC)} and the cytotoxicity-enhancing effects of (±)-ar-turmerone and the extracts of the crude drugs {Lithospermum erythrorhizon(LE) and Scutellaria baicalensis(SB)}on the above mentioned anticancer drugs against HL-60 and KG-1 cells among 8 anticancer drugs, VCR, VBL, ADR, and CPDD inhibited the growth of both cell lines by more than 50% while VP-16, ara-C, Bleo, and CYC were less effective. (±)-ar-Turmerone had significant inhibitory effects against both cell lines, showing the ID_50 values of 11.730 ㎍/㎖ and 0.292 ㎍/㎖ for HL-60 and KG-1 cells. respectively. But the extracts of LE and SB roots showed no significant cytotoxic effects. According to ID_50 values, the cytotoxicities of VCR, VBL and ADR against HL-60 were enhanced two, eight and three times by mixing (±)-ar-turmerone, five, seven and three times by adding the extract of LE root, and twenty, six and three times by mixing the extract of SB root, respectively. The cytotoxicities of the above mentioned drugs against KG-1 cell were enhanced two, seven and three times by mixing (±)-ar-turmerone, two, three and three times by conbining wilth the extract of LB root, and two, five and two times by adding the extract of SB root, respectively. The cytotoxicity-potentiating effects of (±)-ar-turmerone and the extracts of LE and SB roots against HL-60 cell were greater than KG-1 cell.