• Archives of Pharmacal Research
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• 제20권6호
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• pp.572-578
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• 1997

To gain further insight into how antiestrogens modulate cell function, the effects of antiestrogen on cell proliferation were studied in human breast cancer cells. We examined the effects of trans-tamoxifen on the proliferation of three human breast cancer cell lines that differed in their estrogen receptor contents. Trans-tamoxifen $(1{\mu}M)$ markedly inhibited the estrogen stimulated proliferation of MCF-7 human breast cancer cells that contained high levels of estrogen receptor $(1.15{\pm}0.03 pmole/mg protein)$ over that of control. In T47D cells that contained low levels of estrogen receptor $(0.23{\pm}0.05 pmole/mg protein)$, trans-tamoxifen $(1{\mu}M)$ showed minimal inhibition of estrogen stimulated cell proliferation over that of control. MDA-MB-231 cells, that contained no detectable levels of estrogen receptors, had their growth unaffected by trans-tamoxifen treatment. These results showed their sensitivity to growth inhibition by antiestrogen conrrelated well with their estrogen receptor content. Also we examined the effect of antiestrogen on cellular progestrone receptor level as well as plasminogen activator activity in MCF-7 cells. Trans-tamoxifen $(1{\mu}M)$ showed maximal inhibition of estrogen stimulated progestrone receptor level as well as plasminogen activator activity in MCF-7 cells that were stimulated by estrogen. It is not clear whether these inhibitions of progestrone receptor and plasminogen activator activity by estrogen are related to the antiestrogen inhibition of cell proliferation of MCF-7 cells. From the results of this study, it is clearly demonstrated that trans-tamoxifen is an antiestrogen in MCF-7 human breast cancer cells. Our data suggest that the biological effectiveness of trans-tamoxifen appear to result from its affinity of interaction with the estrogen receptor.

• Archives of Pharmacal Research
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• 제20권6호
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• pp.579-585
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• 1997

To gain further insight into the mechanism of action of antiestrogens, we examined the interaction of antiestrogen with the estrogen receptor system and with estrogen- noncompetable antiestrogen binding sites. In addition to binding directly to the estrogen receptor, antiestrogens can be found associated with binding sites that are distinct from the estrogen receptor. In contrast to the restriction of estrogen receptors to estrogen target cells, such as those of uterus and mammary glands, antiestrogen binding sites are present in equal amounts in estrogen receptor-positive and -negative human breast cancer cell lines, such as MCF-7, T47D, and MDA-MB-231 that differ markedly in their sensitivity to antiestrogens. In order to gain greater insight into the role of these antiestrogen binding sites in the action of antiestrogens, we have examined the biopotency of different antiestrogens for the antiestrogen binding sites and that is CI628 > tamoxifen > trans-hydroxy tamoxifen > CI628M > H1285 > LY117018. This order of affinities does not parallel the affinity of these compounds for the estrogen receptor nor the potency of these compounds as antiestrogens. Indeed, compounds with high affinity for the estrogen receptor and greatest antiestrogenic potency have low affinities for these antiestrogen binding sites. Antiestrogenic potency correlates best with estrogen receptor affinity and not with affinity for antiestrogen binding sites. In summary, our findings suggested that interaction with the estrogen receptor is most likely the mechanism through which antiestrogens evoke their growth inhibitory effects.

• Journal of Ginseng Research
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• 제47권1호
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• pp.155-158
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• 2023

In the present study, we investigated whether treatment with KRG improve the parameters of immune activity such as the cytotoxicity, populations of CD4⁺ CD8⁺T cell, CD3^-CD172^-CD8⁺ NK cell and CD172⁺ monocyte as well as natural cytotoxicity receptors such as Nkp46, Nkp44, Nkp30. In results, KRG significantly increased these immune activities. These results indicate that KRG has distinct immuneenhancing effects by increasing the roles of T cells and NK cell in porcine.

• Mycobiology
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• 제47권2호
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• pp.207-216
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• 2019

Talaromyces marneffei is the only dimorphic species in its genus and causes a fatal systemic mycosis named talaromycosis. Our previous study indicated that knockdown of AcuD gene (encodes isocitrate lyase of glyoxylate bypass) of T. marneffei by RNA interference approach attenuated the virulence of T. marneffei, while the virulence of the AcuD knockout strains was not studied. In this study, T. marneffei-zebrafish infection model was successfully established through hindbrain microinjection with different amounts of T. marneffei yeast cells. After co-incubated at $28^{\circ}C$, the increasing T. marneffei inoculum doses result in greater larval mortality; and hyphae generation might be one virulence factor involved in T. marneffei-zebrafish infection. Moreover, the results demonstrated that the virulence of the ${\Delta}AcuD$ was significantly attenuated in this Zebrafish infection model.

• 한국임상수의학회지
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• 제30권6호
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• pp.482-485
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• 2013

6년령의 개가 오른쪽 턱 밑의 종괴와 고체온증으로 전북대학교 수의과대학 동물병원에 내원하였다. 정확한 위치와 크기를 측정하기 위해 CT 촬영을 진행하였으며 3D 재구성을 실시하였다. CT 촬영 후 수술적으로 제거하였으며 제거 후 조직검사를 실시한 결과 거대세포 갑상샘 암종으로 확인되었다. 또한 본 환자의 혈액 중 조절 T 세포의 비율을 보기 위해 흐름세포측정기를 이용하여 실험한 결과 38.28%로 정상인 개(8마리 정상 비글견에서 조사한 결과 $7.66{\pm}1.65%$ (P<0.01))에서 보다 높게 나왔다. 보호자가 항암치료는 원하지 않아서 실시하지 못하였으며 수술 7일 후 다시 재발하였으며 혈액검사 결과 심한 백혈구 증가증 및 비재생성 빈혈이 나타났다. 또한 폐전이 부위로 의심되는 부위가 악화되었으며 결국 심한 빈혈과 호흡곤란으로 폐사하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1241-1245
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• 2015

Background: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, $G47{\Delta}$, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of $G47{\Delta}$. Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with $G47{\Delta}$ at different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either $G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results: $G47{\Delta}$ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to $G47{\Delta}$, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to $G47{\Delta}$; $G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV $G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro. $G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, $G47{\Delta}$ may hold great promise for thyroid cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.785-791
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• 2014

Crude extracts or phytochemicals obtained from some plants have potential anti-cancer properties. Teucrium persicum is an Iranian endemic plant belonging to the Lamiaceae family which has traditionally been used to relieve abdominal pains. However, the anti-cancer properties of this species of the Teucrium genus have not been investigated previously. In this study, we have used a highly invasive prostate cancer cell line, PC-3, which is an appropriate cell system to study anti-tumor properties of plants. A methanolic extract obtained from T persicum potently inhibited viability of PC-3 cells. The viability of SW480 colon and T47D breast cancer cells was also significantly decreased in the presence of the T persicum extract. Flow cytometry suggested that the reduction of cell viability was due to induction of apoptosis. In addition, the results of wound healing and gelatin zymography experiments supported anti-cell invasion activity of T persicum. Interestingly, sublethal concentrations of T persicum extract induced an epithelial-like morphology in a subpopulation of cells with an increase in E-Cadherin and ${\beta}$-Catenin protein levels at the cell membrane. These results strongly suggest that T persicum is a plant with very potent anti-tumor activity.

• 대한임상검사과학회지
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• 제47권4호
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• pp.298-305
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• 2015

최근 종양을 극복하고자 하는 새로운 접근 방법가운데 하나로, 종양세포내에 발현되는 줄기세포 전사인자들(Oct4, Sox2, KLF4 and Lin28)을 억제하여 종양을 치료하는 연구들이 증가하고 있다. 본 실험은 미분화 전사인자를 표적(조절)하는 microRNA-126을 이용하여 난소종양세포들(6종: HSC832(t)c, Ovcar3, Skov3, PA-1, TOV21G and Tov112D)들 생존과 성장에 어떠한 생물학적 변화를 유도하는지 연구하였다. Scramble과 microRNA-126를 난소종양세포들에 처리 후 세포모양 관찰결과 Skov3를 제외한 난소 종양세포들에서 형태학적 모양 변성과 부유현상을 관찰하였다. CCK-8을 이용한 세포분열능 분석에서 Skov3를 제외한 난소 종양세포들의 분열능력이 점차적으로 감소되는 것을 확인하였다. 특히 Tov112D, Tov21G and PA-1에서 각 시간대별로 뚜렷한 세포분열 능력 감소를 확인할 수 있었다. RT-PCR결과 미분화 전사인자들(Sox2, Lin28)의 발현감소를 확인할 수 있었다. 이러한 결과들은 microRNA-126이 다양한 난소 종양세포들을 표적하여 세포분열능과 사멸을 유도할 수 있는 가역적 환경(유전자 발현조절)을 제공함과 동시에 임상 치료에 대한 분자생물학적 단서를 제공할 수 있을 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6949-6953
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• 2013

Background: Nowadays, the encapsulation of cytotoxic chemotherapeutic agents is attracting interest as a method for drug delivery. We hypothesized that the efficiency of helenalin might be maximized by encapsulation in ${\beta}$-cyclodextrin nanoparticles. Helenalin, with a hydrophobic structure obtained from flowers of Arnica chamissonis and Arnica Montana, has anti-cancer and anti-inflammatory activity but low water solubility and bioavailability. ${\beta}$-Cyclodextrin (${\beta}$-CD) is a cyclic oligosaccharide comprising seven D-glucopyranoside units, linked through 1,4-glycosidic bonds. Materials and Methods: To test our hypothesis, we prepared ${\beta}$-cyclodextrin-helenalin complexes to determine their inhibitory effects on telomerase gene expression by real-time polymerase chain reaction (q-PCR) and cytotoxic effects by colorimetric cell viability (MTT) assay. Results: MTT assay showed that not only ${\beta}$-cyclodextrin has no cytotoxic effect on its own but also it demonstrated that ${\beta}$-cyclodextrin-helenalin complexes inhibited the growth of the T47D breast cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of ${\beta}$-cyclodextrin-helenalin complexes increased. Conclusions: ${\beta}$-Cyclodextrin-helenalin complexes exerted cytotoxic effects on T47D cells through down-regulation of telomerase expression and by enhancing Helenalin uptake by cells. Therefore, ${\beta}$-cyclodextrin could be superior carrier for this kind of hydrophobic agent.

• 대한화장품학회지
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• 제47권2호
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• pp.99-105
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• 2021

본 연구는 울릉도 돌외(Gynostemma pentaphyllum) 잎으로부터 캘러스 유도 및 추출한 후, 피부장벽 기능과 관련된 항염증, 항알러지, 각질세포외막 형성, S. aureus에 의한 각질형성세포 손상 완화 효능을 확인하고자 수행되었다. 돌외 캘러스 추출물의 피부에 대한 항염증 효능을 확인하기 위해, PAR-2 agonist로 활성화된 primary epidermal keratinocyte (HEKa)에서 염증성 사이토카인들의 발현을 확인한 결과, 돌외 캘러스 추출물은 IL-8, IL-25, TSLP 발현을 저해하는 효능이 있는 것을 확인하였다. RBL-2H3 세포를 이용한 β-hexosaminidase assay 시험을 통해 항알러지 효능을 확인한 결과, β-hexosaminidase 방출을 억제하는 효과를 보였다. 또한, 돌외 캘러스 추출물은 HaCaT 세포에서 각질세포외막(cornified envelope) 형성 효과가 있음을 확인하였고, HaCaT 세포와 S. aureus 공배양 실험을 통해 S. aureus에 의한 각질형성세포 생존율 감소를 완화하는 효능이 있음을 확인하였다. 본 연구 결과를 종합해보면, 울릉도 돌외 캘러스 추출물은 항염, 항알러지, S. aureus에 의한 각질세포 손상 완화 효능에 유효한 소재의 가능성을 확인하였고, 피부장벽 개선을 위한 화장품 소재로서 활용 가치가 있을 것으로 판단된다.