• Archives of Pharmacal Research
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• 제23권1호
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• pp.59-65
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• 2000

Cancer development and the efficiency of chemotherapy relies on the patients calcium-related pathological status such as hyper- or hypocalcemica. In the present study, we investigated the effect of extracellular cations such as calcium and magnesium on the therapeutic efficacy of antitumor drugs. The analytic parameters used were cellular drug uptake/excretion and the chemosensitivity of the human breast cancer cell lines, MCF7 and MCF7/ADR. Both calcium and magnesium ions decreased the membrane permeability of cancer cells, which was determined bycell size analysis. These divalent ions also lowered the drug uptake and the cytoplasmic levels of rhodamine 123 and adriamycin, suggesting that they might interfere with the diffusion of these drugs by modifying the physical properties of the cytoplasmic membrane. The acute cytotoxicity of adriamycin after a short period of incubation correlated with changes in its cytoplasmic level. Our results indicate that these extracellular cations might play an important role in the therapeutic activities of anticancer drugs in cancer patients. These results also provide insight a new aspect of chemotherapy, because they suggest that the therapeutic dose of anti-cancer drugs should be modified in cancer-bearing patients presenting with abnormal blood calcium levels.

• 한국식품영양과학회지
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• 제36권4호
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• pp.424-430
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• 2007

인동초를 이용하여 표고균사체를 접종, 배양하여 얻어진 인동초균사체 추출액의 간암세포, 유방암세포, 자궁경부암세포 그리고 고형암의 증식에 미치는 영향을 조사하였다. 3가지 암세포의 형태변화 및 증식 억제에 미치는 영향에서 간암세포와 유방암세포에서 암세포에 대한 특이적 형태변화가 관찰되었고, 특히 간암세포에서 인동초균사체 추출물이 인동초추출물보다 효과적인 것으로 나타났다. 인동초균사체를 간암세포에 3mg/mL로 처리했을 때 $85.60{\pm}4.66%$의 암세포 증식억제율을 나타내어 인동초를 처리한 것보다 암세포 증식 억제율이 61.10% 높았다. 유방암세포에서는 인동초 및 인동초균사체를 처리한 것 모두 높은 암세포 증식억제율을 보였으며, 두 군간의 차이는 미미한 것으로 나타났다. 자궁경부암세포에서는 인동초 및 인동초균사체를 처리한 것 모두 암세포 증식억제율이 미미한 것으로 나타났다. 고형암 억제효과에서는 대조군에 비해 인동초균사체 추출물에서 고형암이 61% 억제되었으며, 인동초균사체가 인동초추출물보다 고형암 억제효과가 30% 더 높은 것으로 나타났다. 히스타민 유리 억제효과를 측정한 결과 compound 48/80처리군에 비해 인동초추출물은 9.07%, 인동초균사체 추출물은 43.05%의 히스타민 분비 억제효과가 있는 것으로 나타났다.

• 생명과학회지
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• 제22권9호
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• pp.1145-1151
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• 2012

아스피린과 아스피린의 deacetylated form인 sodium salicylate (NaSal)은 대장암, 폐암 및 유방암을 비롯한 다양한 암의 항암제 활성을 나타내는 것으로 잘 알려져 있다. A549 폐암 세포주에 저농도의 NaSal과 genistein을 함께 복합 처리시 상승작용에 의해 세포사멸을 증가시켜서 NaSal에 의한 암억제 효과를 증대시킴을 이미 밝힌바 있다. 본 연구에서는 A549가 아닌 다른 암세포주와 in vitro solid tumor model인 multicellular spheroids (MTS)을 이용하여 NaSal과 genistein 복합처리 효과를 조사하였다. NaSal/genistein 복합 처리시 A549 세포주와 마찬가지로 HCT116 세포주에서도 세포사멸이 유도되었지만, MCF-7 세포주에서는 유도되지 않았다. 흥미롭게도, MCF-7 세포주는 MTS로 배양되는 동안 NaSal/genistein 복합 처리에 의해 세포 죽음을 나타내었다. 세포 죽음의 형태는 MCF-7 MTS의 발달 단계에 따라 세포사멸 또는 세포괴사로 나타났다. MCF-7 MTS에서의 세포사멸은 불완전한 양상을 보였다. 즉 염색체가 응축되고 쪼개지지만, 핵막은 여전히 관찰되었다. 이상의 연구 결과 NaSal/genistein 복합처리는 MCF-7 MTS 배양 system에서 불완전한 세포사멸과 세포괴사를 일으킴을 알 수 있었다.

• 셀메드
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• 제10권4호
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• pp.27.1-27.6
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• 2020

Cancer is one of the leading cause of mortality in India as well as worldwide. The management of cancer by conventional therapy has shown life threatening adverse effects. The researchers are now exploring the natural way of treatment. Unani system of medicine have rich literature for cancer and many compound formulations have been described in this system. Unani system of medicine is based on holistic approach and treat human being as a unit with natural herbs, mineral and animal origin drugs. An important compound Unani formulation (CUF) from the literature has been chosen to explore the Unani claim of its anticancer activity. The phytochemical constituents were assessed using standard phytochemical screening method. Antioxidant property of this formulation was assessed by DPPH assay. The DPPH free radical scavenging assay was carried out by colorimetric method and ascorbic acid was taken as a positive control. Three different extracts of CUF on different concentrations were used to screening on human breast cancer (BCC) MCF-7 cell line. For the estimation of in-vitro cytotoxic potency of the investigated extracts was assessed on MTT assay by using trypan blue method and paclitaxel was used as the standard. Hydro-ethanolic (HE) extract showed highest free radical scavenging activity among all extracts. DPPH Assay showed substantial antioxidant activity of these extracts in hydro-ethanol extract at 1㎍ concentration of CUF. The CUF showed antioxidant and anticancer activity. The claim made by Unani physician has been proved.

• Journal of Ginseng Research
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• 제43권4호
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• pp.625-634
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• 2019

Background: Ginsenoside Rg3, a derivative of steroidal saponins abundant in ginseng, has a range of effects on cancer cells, including anti-cell proliferation and anti-inflammation activity. Here, we investigate two long noncoding RNAs (lncRNAs), STXBP5-AS1 and RFX3-AS1, which are hypomethylated and hypermethylated in the promoter region by Rg3 in MCF-7 cancer cells. Methods: The lncRNAs epigenetically regulated by Rg3 were mined using methylation array analysis. The effect of the lncRNAs on the apoptosis and proliferation of MCF-7 cells was monitored in the presence of Rg3 or Korean Red Ginseng (KRG) extract after deregulating the lncRNAs. The expression of the lncRNAs and their target genes was examined using qPCR and Western blot analysis. The association between the expression of the target genes and the survival rate of breast cancer patients was analyzed using the Kaplan-Meier Plotter platform. Results: STXBP5-AS1 and RFX3-AS1 exhibited anti- and pro-proliferation effects, respectively, in the cancer cells, and the effects of Rg3 and KRG extract on apoptosis and cell proliferation were weakened after deregulating the lncRNAs. Of the genes located close to STXBP5-AS1 and RFX3-AS1 on the chromosome, STXBP5, GRM1, RFX3, and SLC1A1 were regulated by the lncRNAs on the RNA and protein level. Breast cancer patients that exhibited a higher expression of the target genes of the lncRNAs had a higher metastasis-free survival rate. Conclusion: The current study is the first to identify lncRNAs that are regulated by the presence of Rg3 and KRG extract and that subsequently contribute to inhibiting the proliferation of cancer cells.

• BMB Reports
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• 제29권4호
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• pp.314-320
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• 1996

The effects of non-cytotoxic concentrations of tamoxifen, verapamil, and trifluoperazine on doxorubicin cytotoxicity in five human breast cancer cell lines were studied. A non-cytotoxic concentration of tamoxifen resulted in enhanced doxorubicin cytotoxicity in HTB-123, HTB-26, and MCF-7. In these three cell lines, a combination of tamoxifen with verapamil resulted in even more increased doxorubicin cytotoxicity. Addition of verapamil or trifluoperazine alone did not influence the doxorubicin cytotoxicity significantly. Only in HTB-19 did coincubation with verapamil increase the doxorubicin cytotoxicity. In HTB-123, combination of tamoxifen with trifluoperazine increased the doxorubicin cytotoxicity significantly. In the cell lines where co-incubation with tamoxifen increased doxorubicin sensitivity, high estrogen receptor expression was detected. However, HTB-20, where tamoxifen did not enhance doxorubicin action, was also estrogen receptor positive. None of the cell lines had multidrug resistance related drug efflux and drug retention was not increased by the treatment with tamoxifen and verapamil. Cell cycle traverses were not altered by incubation with tamoxifen, verapamil or combinations thereof. These observatlons suggest mechanism of non-cytotoxic concentrations of tamoxifen and verapamil on doxorubicin cytotoxicity may involve one or more other cellular processes besides those of interference of estrogen binding to its receptor, cell cycle perturbation, or drug efflux blocking.

• 한국식품영양학회지
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• 제22권4호
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• pp.485-491
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• 2009

In order to examine the nutritional value of prickly pear(Opuntia humifusa), contents of ash, protein, fat, minerals and vitamins were determined on freeze-dried stem, fruit, seed and root from plants harvested in autumn. The average moisture contents for stem, fruit, seed and root were 67~87%. Crude ash content determined on dry weight basis was 2~3%. Crude protein existed mostly in seed(2.95%) and root(2.37%). Crude fat was detected mainly in seed(4.49%). Contents of major minerals(mg/100 mg dry weight) was generally higher in stem. Ca in stem(4,142.30) and fruit(2,790.86) were much higher than in seed(43.37). P in stem, seed and fruit were 448.19, 263.20 and 161.59, respectively. Stem also displayed more abundant Mg(1,110.86), Zn(35.62) and Mn(37.07). However, fruit contained higher amounts of Fe(13.38) and Se(0.15). Vitamin A was negligible in all plant parts. Vitamin E contents in fruit and stem were 1.78 mg and 1.22 mg/mg dry weight, respectively. Vitamin C was detected mostly in fruit(445.40) and stem(260.94). Use of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based microtiter assay of cell viability demonstrated an anti-proliferative effect of O. humifusa extract on the MCF-7 estrogen-dependent human breast cancer cell line.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.171-171
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• 2002

Recent industrial society has human widely exposed to PAHs that are comming from the incomplete combustion of organic material as widerspread environmetal contaminants. Biological activities of PAHs are not known although PAHs are considered as carcinogens. PAHs in the mammalian cells affect CYP1A1 gene expression as well as other phase II drug metabolizing enzymes as UDPGT, NMOR etc. The mechanism of action of PAHs has been studied extensively, however it is not clear how PAHs turn on CYP1A1 in human breast cancer. Our labolatory have been studied the effect of PAHs in the human breast cancer cell lind MCF7. In this study, we examined the ZR-75-1 human breast cancer cells as a new system to evaluate bioactivity of PAHs. ZR-75-1 human breast cancer cell line has been estabilished from the breast cnacer patient, has estrogen receptors and progesteron receptors. We have been able to estbilish long term culture system of this cells then used for the study to observe the effect of PAHs. We demonstrate that PAHs induced the transcription of an aryl hydrocarbon-responsive reporter vector containing the CYP1A1 promoter and 7-ethoxyresolufin O-deethylase(EROD) activity of CYP1A1 enzyme in a concentration-dependant manner. RT-PCR analysises indicated that PAHs significantly up-regulate the constitutive level of CYP1A1 mRNA. Apparently, ZR-75-1 cells have Aryl hydrocarbon recetors, therefore it would be good experimental tool to study the cross-talk between PAHs and steroid actions.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2439-2445
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• 2014

Cryptotanshinone (CPT), is a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miotiorrhiza bunge. Numerous researchers have found that it could work as a potent antitumor agent to inhibit tumor growth in vitro, buith there has been much less emphasis on its in vivo role against breast tumors. Using a mouse tumor model of MCF7 cells, we showed that CPT strongly inhibited MCF7 cell growth in vivo with polarization of immune reactions toward Th1-type responses, stimulation of naive CD4+ T cell proliferation, and also increased IFN-${\gamma}$ and perforin production of CD4+ T cells in response to tumor-activated splenocytes. Furthermore, data revealed that the cytotoxic activity of CD4+ T cells induced by CPT was markedly abrogated by concanamycin A(CMA), a perforin inhibitor, but not IFN-${\gamma}$ Ab. On the other hand, after depletion of CD4+ T cells or blocked perforin with CMA in a tumor-bearing model, CPT could not effectively suppress tumor growth, but this phenomenon could be reversed by injecting naive CD4+ T cells. Thus, our results suggested that CPT mainly inhibited breast tumor growth through inducing cytotoxic CD4+ T cells to secrete perforin. We further found that CPT enhanced perforin production of CD4+ T cells by up-regulating JAK2 and STAT4 phosphorylation. These findings suggest a novel potential therapeutic role for CPT in tumor therapy, and demonstrate that CPT performs its antitumor functions through cytotoxic CD4+ T cells.

• 생명과학회지
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• 제13권3호
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• pp.314-323
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• 2003

지금까지 estrogen 호르몬이 유방암의 발생과 진전에 관여한다는 사실을 뒷받침 할 수 있는 여러 가지 증거가 제시되어 왔지만, 암화에 관여하고 있는 estrogen의 분자생물학적 작용기전에 대해서는 아직 명확히 알려져 있지 않다. 유방암 세포의 발암현상은 다양한 핵 수용체들과 이들 각각의 신호전달경로들 사이의 기능적 상호교류 (Functional Cross-talk)에 의해 조절되는 것으로 추측되고 있다. 그러므로, 유방암세포의 성장과 증식에 관여하는 신호전달경로중에서 estrogen의 작용을 조절할 수 있는 핵 수용체를 밝혀내고, 이러한 수용체와 estrogen receptor사이에 어떠한 기능적 상호교류가 일어나는지를 규명하는 것은 암화와 관련된 estrogen의 분자생물학적 작용기전을 이해하는 데 중요한 진전을 가져올 수 있다. 따라서 본 연구의 목적은 유방암세포 내에서 estrogen의 작용이 xenobiotic nuclear receptor에 의해 조절되는지를 규명하기 위하여, 두 종류의 유방암세포인 estrogen receptor가 발현되는 MCF-7 세포와 ER의 발현이 일어나지 않는 MDA-MB-231세포를 배양하여, 에스트로겐에 의해 전사가 촉진되는 보고유전자의 발현이 CAR, SXR, 그리고 PPAR${\gamma}$에 의해서 어떻게 영향을 받는지를 조사하고 그 결과를 간암세포에서의 반응과 비교 분석하였다. 최근에 보고된 연구결과와 일치하게, xenobiotic nuclear receptor가 간세포에서 일어나는 에스트로겐 수용체의 신호전달경로에 영향을 줄 수 있음을 확인하였다. PPAR${\gamma}$를 제외한 핵 수용체 CAR와 SXR은 ER의 전사활성 효과를 현저하게 또는 어느 정도 각각 감소시켰다. Hep G2세포에서와는 달리 유방암세포에서는 조사된 세가지의 xenobiotic 핵 수용체가 ER의 전사활성에 그다지 영향을 미치지 않거나 유방암세포의 종류와 각각의 수용체에 따라서 다소 촉진하는 경향을 나타내었다. MCF-7 세포에서는 CAR와 PPAR${\gamma}$을 제외한 SXR이 ER의 transactivation 효과를 약간 촉진한 반면 MDA-MB-231세포는 SXR을 제외한 CAR와 PPAR${\gamma}$에 의해 ER의 transactivation 효과가 약간 증가되는 경향을 보였다. 이러한 결과는 유방암세포에서는 CAR, SXR, PPAR${\gamma}$과 같은 xenobiotic nuclear receptor에 의한 ER transactivation 효과가 간암세포와는 다르게 나타나며, 유방암의 종류에 따라서 endogenous CAR, SXR, PPAR${\gamma}$수용체가 다르게 발현됨으로써 이들에 대한 반응이 서로 상이한 특징을 나타낼 수 있을 것으로 사료된다. 따라서 estrogen receptor에 의해 매개되는 estrogn의 전사활성조절기전이 표적세포에 따라 다른 경로를 포함 할 수 있음을 시사한다.