• 동의생리병리학회지
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• 제19권6호
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• pp.1552-1556
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• 2005

Silymarin has been known to exert anti-tumoral activity in Korea. However, its molecular mechanism of action is not understood. In this study, we found that silymarin induced apoptosis in androgen-independent prostate cancer DU145 cells as confirmed by DNA fragmentation. Our data demonstrated that silymarin-induced apoptotic cell death was accompanied by activation of caspase-3 and subsequent cleavages of its substrates, poly(ADP-ribose) polymerase (PARP) in a time- and concentration-dependent manner. Also, silymarin-induced apoptotic mechanism of DU145 cells involved the induction of Par-4 protein expression. Taken together, these results suggest that silymarin induces the activation of caspase-3, degradation of PARP, increase of Par-4 expression, and eventually leads to apoptotic cell death.

• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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• pp.5031-5035
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• 2016

Docetaxel, recognized as a stabilizing microtubule agent, is frequently administrated as a first line treatment for prostate cancers. Due to high side effects of monotherapy, however, combinations with novel adjuvants have emerged as an alternative strategy in cancer therapy protocols. Here, we investigated the combined effects of stattic and docetaxel on the DU145 prostate cancer cell line. Cytotoxicity was evaluated by MTT assay. To understand molecular mechanisms of stattic action, apoptotic related genes including Bcl-2, Mcl-1, Survivin and Bax were evaluated by real-time RT-PCR. Alteration in the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 genes and Bax/Bcl-2 ratio were investigated via the $2^{{\Delta}{\Delta}CT}$ method. The $IC_{50}$ values for docetaxel and stattic were $3.7{\pm}0.9nM$ and $4.6{\pm}0.8{\mu}M$, respectively. Evaluation of key gene expression levels revealed a noticeable decrease in antiapoptotic Bcl-2 and Mcl-1 along with an increase in pro-apoptotic Bax mRNA levels (p<0.05). Our results suggest that combination of a STAT3 inhibitor with doctaxel can be considered as a potent strategy for induction of apoptosis via increasing Bax mRNA expression.

• Radiation Oncology Journal
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• 제27권4호
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• pp.218-227
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• 2009

목 적: 전립샘암 세포주 DU 145에서 엑스선과 중성자선에 의한 HIF-$1\alpha$와 아포프토시스 발현의 차이를 비교함으로써 엑스선과 중성자선의 방사선생물학적 차이의 기전을 알아보고자 한다. 대상 및 방법: 누드 마우스에 DU 145 전립샘암 세포주를 주입한 후 2 Gy 엑스선, 10 Gy 엑스선, 0.6 Gy 중성자선, 3.3 Gy 중성자선을 각각 조사했다. 엑스선을 조사한 군과 중성자선을 조사한 군에서 HIF-$1\alpha$, Bcl-2, Bax, 아포프토시스 발현 정도를 면역조직화학 염색과 western blotting을 이용하여 비교하였다. 아포토시스의 정도는 terminal deoxynucleotidyl biotin-dUTP nick end labeling (TUNEL) 염색을 이용하여 비교하였다. 결 과: 방사선 조사 1일째, X선을 조사한 군과 비교했을 때, 중성자선을 조사한 군에서 HIF-$1\alpha$와 Bcl-2의 발현은 감소하였고, Bax와 아포프토시스 세포의 수는 증가하였다. Bcl-2/Bax 비는 중성자선을 조사한 군에서 의미 있게 감소하였다. 이러한 HIF-$1\alpha$, Bcl-2, Bax, Bcl-2/Bax 비, 아포프토시스 발현의 차이는 방사선 조사 5일째에도 동일하게 유지되어 나타났다. 또한, HIF-$1\alpha$ 발현은 방사선 조사 5일째 Bcl-2 (p=0.031), Bax (p=0.037), TUNEL (p=0.016) 발현과 연관성을 보였다. 결 론: 중성자선 조사한 경우 엑스선에 비해 HIF-$1\alpha$와 Bcl-2 발현, Bcl-2/Bax 비가 감소하고, Bax 발현은 증가하였다. 중성자선 치료의 광자선과 다른 방사선생물학적인 반응은 HIF-$1\alpha$와 그로 인한 아포프토시스 관련 단백질 발현의 차이와 연관성이 있을 것으로 생각한다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.101-101
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• 1997

As part of a drug discovery program to develope more effective platinum-based anticancer drugs, a series of platinum complexes trans -diaminocyclohexane platinum bi sdiphenylphosphino -ethane (KHPC-002) cis-diaminocyclohexane platinum bisdiphenylphosphino-ethane (KHPC-006) has been evaluated in vitro against 4 human carcinoma cell lines with those of cisplatin using a tetrazolium-based colorimetric assay (MTT assay). The cell lines were two human bladder carcinoma cell lines, HT-1197 and HT-1376, human colon carcinoma cell line, HCT-116, and prostate cancer cell line DU-145.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.111-111
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• 1997

As part of a drug discovery program to develope more effective platinum-based anticancer drugs, a series of platinum complexes trans-diaminocyclohexane platinum bi sdiphenylphosphino - ethane ( KHPC- 002) cis-diaminocyclohexane platinum bi sdiphenylphosphino - ethane ( KHPC- 006) has been evaluated in vitro against 4 human carcinoma cell lines with those of cisplatin using a tetrazolium-based colorimetric assay (MTT assay). The cell lines were two human bladder carcinoma cell lines, HT-1197 and HT-1376, human colon carcinoma cell line, HCT-116, and prostate cancer cell line DU-145. in vitro cytotoxic potential of each platinum complex was expressed as the cytotoxicity index (Cl, %).

• 약학회지
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• 제43권3호
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• pp.369-377
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• 1999

A new series of highly water soluble platinum(II) complexes {Pt(II)[1,3-bis(phenylthio) propane](trans- -1,2-diaminocyclohexane) (PC-1) and Pt(II)[1,3-bis-(phenythio)propane] cis-1,2-diaminocyclohexane(PC-2)} were synthesized, and characterized by their elemental analysis and by various spectroscopic techniques[infrared(IR), 13C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II) complexes was tested against P-388 and L-1210 mouse lymphocytic leukemia cell lines, PC-14 / P, PC-14/ADM and PC-14 / CDDP human pulmonary adenocarcinima, DU-145 human prostate carcinoma, HT-1376 human bladder carcinoma, ZR-75-1 human breast carcinoma, MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2.5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 showed active against L-1210, P-388 leukemia, human lung, stomach, prostate, bladder and breast cancer cell lines, and the antitumor activity of these compounds were comparable or superior to those of PC-2 and displatin. The nephrotoxicities of PC-1 and PC-2 were found quite less than that of cisplatin using MTT and [3H] thymidine uptake in rabbit proximal tubule cells and human kidney cortical cells. Based on these results, this novel platinum (II) complex compound (PC-1) represents a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.403-411
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• 2009

Thiacremonone, the main component isolated from heated garlic (Allium sativum L.), is interested for using as a cancer preventive or therapeutic agent since garlic has been known to be useful plant in the treatment of cancers. Nuclear factor kappaB (NF-${\kappa}B$) is constitutively activated in the prostate cancer and activation of NF-${\kappa}B$ is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of paclitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-${\kappa}B$ in cancer cells and marcrophages. In the present study, we investigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-${\kappa}B$. We found that the combination treatment of thiacremonone (50 ${\mu}g$/ml) with docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis accompanied with the significant inhibition of NF-${\kappa}B$ activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-${\kappa}B$ target gene expression of Bax, caspase-3 and caspase-9 was much more significantly enhanced, but the expression of Bcl-2 was also much more significantly inhibited by the combination treatment. These results indicate that thiacremonone inhibits NF-${\kappa}B$, and enhances the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.

• Nutrition Research and Practice
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• 제5권3호
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• pp.185-191
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• 2011

In Korea, chestnut production is increasing each year, but consumption is far below production. We investigated the effect of chestnut extracts on antioxidant activity and anticancer effects. Ethanol extracts of raw chestnut (RCE) or chestnut powder (CPE) had dose-dependent superoxide scavenging activity. Viable numbers of MDA-MD-231 human breast cancer cells, DU145 human prostate cancer cells, and AGS human gastric cancer cells decreased by 18, 31, and 69%, respectively, following treatment with $200{\mu}g/mL$ CPE for 24 hr. CPE at various concentrations ($0-200{\mu}g/mL$) markedly decreased AGS cell viability and increased apoptotic cell death dose and time dependently. CPE increased the levels of cleaved caspase-8, -7, -3, and poly (ADP-ribose) polymerase in a dose-dependent manner but not cleaved caspase-9. CPR exerted no effects on Bcl-2 and Bax levels. The level of X-linked inhibitor of apoptosis protein decreased within a narrow range following CPE treatment. The levels of Trail, DR4, and Fas-L increased dose-dependently in CPE-treated AGS cells. These results show that CPE decreases growth and induces apoptosis in AGS gastric cancer cells and that activation of the death receptor pathway contributes to CPE-induced apoptosis in AGS cells. In conclusion, CPE had more of an effect on gastric cancer cells than breast or prostate cancer cells, suggesting that chestnuts would have a positive effect against gastric cancer.

• Nutrition Research and Practice
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• 제8권3호
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• pp.257-266
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• 2014

BACKGROUND/OBJECTIVE: Licorice has been shown to possess cancer chemopreventive effects. However, glycyrrhizin, a major component in licorice, was found to interfere with steroid metabolism and cause edema and hypertension. The roasting process of licorice modifies the chemical composition and converts glycyrrhizin to glycyrrhetinic acid. The purpose of this study was to examine the anti-carcinogenic effects of the ethanol extract of roasted licorice (EERL) and to identify the active compound in EERL. MATERIALS/METHODS: Ethanol and aqueous extracts of roasted and un-roasted licorice were prepared. The active fraction was separated from the methylene chloride (MC)-soluble fraction of EERL and the structure of the purified compound was determined by nuclear magnetic resonance spectroscopy. The anti-carcinogenic effects of licorice extracts and licochalcone A was evaluated using a MTT assay, Western blot, flow cytometry, and two-stage skin carcinogenesis model. RESULTS: EERL was determined to be more potent and efficacious than the ethanol extract of un-roasted licorice in inhibiting the growth of DU145 and MLL prostate cancer cells, as well as HT-29 colon cancer cells. The aqueous extracts of un-roasted and roasted licorice showed minimal effects on cell growth. EERL potently inhibited growth of MCF-7 and MDA-MB-231 breast, B16-F10 melanoma, and A375 and A2058 skin cancer cells, whereas EERL slightly stimulated the growth of normal IEC-6 intestinal epithelial cells and CCD118SK fibroblasts. The MC-soluble fraction was more efficacious than EERL in inhibiting DU145 cell growth. Licochalcone A was isolated from the MC fraction and identified as the active compound of EERL. Both EERL and licochalcone A induced apoptosis of DU145 cells. EERL potently inhibited chemically-induced skin papilloma formation in mice. CONCLUSIONS: Non-polar compounds in EERL exert potent anti-carcinogenic effects, and that roasted rather than un-roasted licorice should be favored as a cancer preventive agent, whether being used as an additive to food or medicine preparations.

• Preventive Nutrition and Food Science
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• 제11권4호
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• pp.278-284
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• 2006

The beneficial effects of digested onion extracts have been assessed by antimutagenic and anticancer activities by Ames test and SRB test. The total phenolic acids and flavonoids in onion extracts were determined. Red and yellow onions contain more phenolic acids and flavonoids than those in the white onion. Digested, extracts showed antimutagenic activity and anticancer activity, and it appears that the antimutagenic activity of digested extracts of onion against mutagens and anticancer activities were related to their phenols and flavonoids contents. Moreover, the extracts inhibited the proliferation of four human tumorigenic cell lines such as HT-29 (colon), MCF-7 (breast), DU-145 (prostate) and HepG2 (liver), in a dose-dependent manner. Phenolic acids and flavonoids caused oxidative damage to the cancer cell lines and induced apoptosis. Generally, red onion extracts showed effective antimutagenic and anticancer activity, and the digested red onion extracts elicited stronger antimutagenic activity than those of the onion extracts without digestion.