• 생명과학회지
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• 제22권7호
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• pp.964-969
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• 2012

Genistein은 대두 및 그들의 부산물에 풍부하게 존재하는 isoflavone의 일종으로 정상세포에서는 독성을 나타내지 않는 범위에서 다양한 in vitro 및 in vivo 모델에서 암세포의 증식을 효과적으로 억제할 수 있는 천연물로 알려져 있다. 본 연구에서는 MCF-7 및MDA-MB-231 유방암세포에서 matrix metalloproteinases (MMPs)의 활성 및 발현과 침윤성에 미치는 genistein의 영향을 조사하였다. 본 연구의 결과에 의하면 genistein은 12-O-tetradecanoyl phorbol-13-acetate (TPA) 처리에 의하여 활성화된 MMP-2 및 -9의 활성을 유의적으로 차단하였으며, 이는 전사 및 번역 수준에서 MMP-2 및 -9의 발현 억제와 연관성이 있었다. 또한 matrigel invasion assay를 통하여 genistein은 두 유방암세포의 침윤성을 완벽하게 차단하였음을 관찰하였으며, 이러한 효과는 genistein의 세포독성 효과에 의한 것이 아니었음을 알 수 있었다. 비록 in vivo 동물 실험을 통한 부가적인 연구의 필요성이 있으나, 본 연구의 결과는 genistein이 암의 전이를 억제할 수 있는 효과적인 식이 소재임을 보여주는 것이다.

• 대한한방부인과학회지
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• 제22권2호
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• pp.94-118
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• 2009

Purpose: Gleditsiae spina (GS) has been used to treat patients with several diseases such as carbuncle, swelling and parasites. Recently GS is known to have anticancer activity in abdominal solid tumor, but the effects of GS on breast cancers is not clarified. For these reasons, we investigated effects of Gleditsiae spina (GS) on gene expression of human breast cancer cells. Methods: We investigated the effects of GS on proliferation of breast cancer cell line, MDA-MB-231. In addition, the genetic profile for the effect of GS on breast cancer cells was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 1,434 genes were up-regulated and 2,483 genes down-regulated in the cells treated with GS. Genes induced or suppressed by GS were all mainly concerned with metabolic process, regulation of biological process and protein binding. The network of total protein interactions was measured using cytoscape program, and some key molecules that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer drug for breast cancer, and also suggest that related mechanisms are involved in regulation of intra-cellular metabolism in breast cancer cells.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.473-481
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• 2020

Axl receptor tyrosine kinase has been implicated in cancer progression, invasion, and metastasis in various cancer types. Axl overexpression has been observed in many cancers, and selective inhibitors of Axl, including R428, may be promising therapeutic agents for several human cancers, such as breast, lung, and pancreatic cancers. Here, we examined the cell growth inhibition mediated by R428 and auranofin individually as well as in combination in the human breast cancer cell lines MCF-7 and MDA-MB-231 to identify new advanced combination treatments for human breast cancer. Our data showed that combination therapy with R428 and auranofin markedly inhibited cancer cell proliferation. Isobologram analyses of these cells indicated a clear synergism between R428 and auranofin with a combination index value of 0.73. The combination treatment promoted apoptosis as indicated by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. Cancer cell migration was also significantly inhibited by this combination treatment. Moreover, we found that combination therapy significantly increased the expression level of Bax, a mitochondrial proapoptotic factor, but decreased that of the X-linked inhibitor of apoptosis protein. Furthermore, the suppression of cell viability and induction of Bax expression by the combination treatment were recovered by treatment with N-acetylcysteine. In conclusion, our data demonstrated that combined treatment with R428 and auranofin synergistically induced apoptosis in human breast cancer cells and may thus serve as a novel and valuable approach for cancer therapy.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.90-90
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47D and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 추계국제학술대회
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• pp.180-180
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• 2003

The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER Positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47B and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

• 한국자원식물학회지
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• 제29권3호
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• pp.297-304
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• 2016

The seed of safflower (Carthamus tinctorius L) has been reported to suppress human cancer cell proliferation. However, the mechanisms by which safflower seed inhibits cancer cell proliferation have remained nuclear. In this study, the inhibitory effect of the safflower seed (SS) on the proliferation of human colorectal cancer cells and the potential mechanism of action were examined. SS inhibited markedly the proliferation of human colorectal cancer cells (HCT116, SW480, LoVo and HT-29). In addition, SS suppressed the proliferation of human breast cancer cells (MDA-MB-231 and MCF-7). SS treatment decreased cyclin D1 protein level in human colorectal cancer cells and breast cancer cells. But, SS-mediated downregulated mRNA level of cyclin D1 was not observed. Inhibition of proteasomal degradation by MG132 attenuated cyclin D1 downregulation by SS and the half-life of cyclin D1 was decreased in SS-treated cells. In addition, SS increased cyclin D1 phosphorylation at threonine-286 and a point mutation of threonine-286 to alanine attenuated SS-mediated cyclin D1 degradation. Inhibition of ERK1/2 by PD98059 suppressed cyclin D1 phosphorylation and downregulation of cyclin D1 by SS. In conclusion, SS has anti-proliferative activity by inducing cyclin D1 proteasomal degradation through ERK1/2-dependent threonine-286 phosphorylation of cyclin D1. These findings suggest that possibly its extract could be used for treating colorectal cancer.

• KSBB Journal
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• 제32권3호
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• pp.224-232
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• 2017

Resveratrol has been actively investigated as an anticancer drug since it induces cell growth inhibition and apoptosis in many cancer cells. Resveratrol acts through modulation of multiple pathways and genes. In this study, we found resveratrol reduced cell growth and mammosphere formation in MDA-MB-231 triple-negative human breast cancer cells. This suppressive effect of resveratrol is accompanied by a reduction in Bmi-1 gene expression. We also observed that knock-down of Bmi-1 gene by small interfering RNA effectively sensitizes breast cancer cells to resveratrol treatment. Our data demonstrate, for the first time, that resveratrol down-regulates Bmi-1 expression in human breast cancer cells and suggest that specific molecular targeting of Bmi-1 can be combined with a chemotherapeutic strategy to improve the response of breast cancer cells to resveratrol.

• 한국식품영양과학회지
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• 제31권4호
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• pp.691-695
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• 2002

한국산 솔잎을 가압.압착하여 얻은 수액을 증류한 솔잎 수액 증류액의 각종 암세포주에 대한 in uitro 세포독성을 시료액 대비 10배, 20배, 40배 희석군과 대조군에 대해 XTT법으로 실험한 결과, 쥐 백혈병 세포주인 L1210에 대해서는 76~89%, 쥐 육종암세포인 sarcoma 180에 대해서는 61~90%의 세포성장 억제효과를 나타내었다. 또한 인체의 monocyte-like cancer cell인 U937에 대해서는 56~81%, 인체 유방암 세포주인 T47D와 MDA-MB-231에서는 각기 12%, 또 다른 유방암 세포주인 MH7A에서는 64%, 인체 간암 세포주인 SNU-354에 대해서는 72%의 높은 세포 증식 억제효과를 나타내었다. 이로써 본 연구 시료인 솔잎 수액 증류액은 쥐 백혈병 세포주인 L1210, 쥐 육종암세포인 sarcoma 180, 인체 monocyte-like cancer cell인 U937, 인체 유방암 세포주인 MH7A, 인체 간암 세포주인 SNU-354에 대해 강한 세포독성을 갖는 것을 알 수 있었다. 이와 함께 솔잎 수액 증류액의 암세포에 대한 독성효과는 솔잎의 처리과정에 따라 다를 수 있으며, 또한 동일한 솔잎 수액증류액의 농도에서도 암세포주 종류에 따라 세포독성정도가 다름을 알 수 있었다. 따라서 최적 투여 농도와 적용 암세포주를 찾을 경우 새로운 항암제로 개발될 수 있음을 제시하였다.

• Journal of Ginseng Research
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• 제43권4호
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• pp.692-698
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• 2019

Background: Breast cancer is a severe disease and the second leading cause of cancer death in women worldwide. To surmount this, various diagnosis and treatment options for breast cancer have been developed. One of the most effective strategies for cancer treatment is to induce apoptosis using naturally occurring compounds. Compound K (CK) is a ginseng saponin metabolite generated by human intestinal bacteria. CK has been studied for its cardioprotective, antiinflammatory, and liver-protective effects; however, the role of CK in breast cancer is not fully understood. Methods: To investigate the anticancer effects of CK in SKBR3 and MDA-MB-231 cells, cell viability assays and flow cytometry analysis were used. In addition, the direct targets of CK anticancer activity were identified using immunoblotting analysis and overexpression experiments. Invasion, migration, and clonogenic assays were carried out to determine the effects of CK on cancer metastasis. Results: CK-induced cell apoptosis in SKBR3 cells as determined through 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assays, propidium iodide (PI) and annexin V staining, and morphological changes. CK increased the cleaved forms of caspase-7, caspase-8, and caspase-9, whereas the expression of Bcl-2 was reduced by CK. In assays probing the cell survival pathway, CK activated only AKT1 and not AKT2. Moreover, CK inhibited breast cancer cell invasion, migration, and colony formation. Through regulation of AKT1 activity, CK exerts anticancer effects by inducing apoptosis. Conclusion: Our results suggest that CK could be used as a therapeutic compound for breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6869-6874
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• 2013

Background: Vascular endothelial growth factor and matrix metalloproteinases are two important factors for angiogenesis associated with breast cancer growth and progression. The present study was aimed to examine the effects of tamoxifen and tranilast drugs singly or in combination on proliferation of breast cancer cells and also to evaluate VEGF and MMP-9 expression and VEGF secretion levels. Materials and Methods: Human breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with tamoxifen and/or tranilast alone or in combination and percentage cell survival and proliferative activity were evaluated using LDH leakage and MTT assays. mRNA expression and protein levels were examined by real-time RT-PCR and ELISA assay, respectively. Results: LDH and MTT assays showed that the combined treatment of tamoxifen and tranilast resulted in a significant decrease in cell viability and cell proliferation compared with tamoxifen or tranilast treatment alone, with significant decrease in VEGF mRNA and protein levels. We also found that tamoxifen as a single agent rarely increased MMP-9 expression. A decrease in MMP-9 expression was seen after treatment with tranilast alone and in the combined treatment MMP-9 mRNA level was decreased. Conclusions: This combination treatment can able to inhibit growth, proliferation and angiogenesis of breast cancer cells.