• 한국식품영양과학회지
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• 제41권12호
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• pp.1701-1707
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• 2012

3,3'-Diindolylmethane(DIM)은 십자화과 채소에 포함되어 있는 indole-3-carbinol(I3C)이 동물의 산성 위액에서 중합되어 생성된 물질이다. 지금까지 DIM은 유방암, 전립선암 그리고 대장암 세포주에서 항암효과가 있다고 알려져 있으며 그 기작에 대한 연구도 다양하게 진행되고 있다. 그러나 정상세포에서 암화과정 중 암의 촉진과 진행과정의 주요한 항암 표적인 항염증에 대한 연구는 보고된 바 없다. 따라서 본 연구에서는 유방상피세포인 MCF-10A 세포에 12-O-tetradecanoylphorbol-13-acetate(TPA)로 염증반응을 유도한 후 DIM이 염증작용에 미치는 영향을 조사하였다. 그 결과 MCF-10A 세포에서 TPA에 의해 유도된 COX-2 단백질 및 mRNA 발현이 DIM 처리에 의해 현저히 감소하였다. 또한 TPA에 의해 유도된 $I{\kappa}B-{\alpha}$의 분해, p65의 핵으로의 이동, $NF-{\kappa}B$ DNA binding activity 역시 DIM의 처리에 의해 감소하였다. 이는 DIM이 인간의 유방상피세포인 MCF-10A 세포에서 TPA에 의해 유도된 $NF-{\kappa}B$ 신호전달체계의 활성을 억제함으로써 COX-2의 발현을 억제하여 염증반응을 조절함을 나타낸다. 그러므로 이러한 결과들은 DIM을 염증성 질환 예방제 또는 치료제로 개발할 수 있는 가능성을 시사한다.

• 대한세포병리학회지
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• 제18권2호
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• pp.157-160
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• 2007

Granular cell tumor (GCT) of the breast is a rare clinical entity, and is believed to be of schwannian origin and to follow a benign clinical course. A 50-year-old woman presented with a slowly growing mass in the right breast. Fine needle aspiration cytology revealed a cellular smear containing isolated or clustered cells showing round to oval nuclei with abundant oncocytic granular cytoplasm. Nuclei showed a fine granular chromatin pattern and occasional small single nucleoli. Cell boundaries were poorly defined, and naked nuclei were frequently found, Histologically, the tumor showed features of typical GCT, and immunohistochemical staining findings strongly supported the diagnosis. The present study demonstrates that GCT of the breast can mimic malignant lesions of breast both clinically and radiologically. The recognition of its cytologic features and suspicion of this lesion would undoubtedly aid the correct diagnosis of mammary GCT.

• Journal of Yeungnam Medical Science
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• 제35권1호
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• pp.99-103
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• 2018

Mammary Paget's disease (MPD) is usually accompanied by underlying breast malignancy; however, a few cases have been reported as only skin lesions without any evidence of malignancy of the breast on imaging tests and microscopic examination of surgical specimen. Here, we describe a 47-year-old woman who visited our hospital who had an eczematous lesion on right nipple and areola for over 10 years. The lesion was diagnosed as Paget's disease by punch biopsy; however, imaging studies demonstrated no breast malignancy or lymph node metastasis. The patient underwent surgery of on the nipple and areola including underlying breast tissue. No underlying malignancy was found upon microscopic examination, except for Paget's disease. Immunohistochemical stains revealed that the tumor cells were positive for cytokeratin 7, and negativity for p63, cytokeratin 5/6, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. We report a case of MPD without underlying malignancy. To the best of our knowledge, this is the third case reported in Korea.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2765-2770
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• 2012

Background: There is a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. Here we investigated the antiproliferative properties of Melissa officinalis (MO) from Turkey on breast cancer. Methods: MO extracts were studied for cytotoxicity against breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). In vitro apoptosis studies were performed by annexin V staining and flow cytometry analyses. Immunohistochemistry for Ki-67 and caspase 7 in the tumoral tissue sections of DMBA-induced mammary tumors in rats was also performed, along with TUNEL assays to detect apoptotic cells. In vivo anticancer activity testing was carried out with reference to inhibition of growth of DMBA induced mammary tumors in rats. Results: MO showed cytotoxicity against three cancer cell lines, inducing increase in Annexin-positive cells. Expression of caspase-7 protein and TUNEL positive cells were much higher in rats treated by MO, compared with the untreated control group, while expression of Ki-67 was decreased. Furthermore, in vivo studies showed that mean tumor volume inhibition ratio in MO treated group was 40% compared with the untreated rats. Conclusion: These results indicated that MO extrcts have antitumoral potential against breast cancer.

• Natural Product Sciences
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• 제23권1호
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• pp.21-28
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• 2017

In our program to search for new AMP-activated protein kinase (AMPK) activators from plants that exert potential anticancer property, we found that an EtOAc extract of Myristica fragrans (nutmeg) activated AMPK enzyme in human breast cancer MCF-7 cells. Two major diarylbutane-type lignans, macelignan and meso-dihydroguaiaretic acid (MDGA), were isolated as active principles from this extract. Treatment of breast cancer cells with two compounds induced cellular apoptosis, evidenced by cleavage of poly-(ADP-ribose) polymerase (PARP) and Ser 15 phosphorylation of p53. Moreover, macelignan and MDGA significantly inhibited the colony formation of MCF-7 breast cancer cells on soft agar. Intraperitoneal injection of macelignan and MDGA (20 mg/kg) suppressed the tumor growth of 4T1 mammary cancer cells. These results indicate that the chemopreventive effects of two major diarylbutane-type lignans from Myristica fragrans (nutmeg) may be associated with induction of apoptosis presumably through AMPK activation.

• Radiation Oncology Journal
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• 제34권3호
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• pp.223-229
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• 2016

Purpose: This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and $HIF-1{\alpha}$ positivity in tumor cells were decreased when treated with captopril. Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.

• 한국환경성돌연변이발암원학회지
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• 제19권1호
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• pp.56-62
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• 1999

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) has been considered to be as one of major antioxidants present in grapes responsible for beneficial effects of red wine consumption on coronary heart disease. This triphenolic stilbene has been suggested as a potential cancer chemopreventive agent based on its striking inhiitory effects on diverse cellular events associated with tumor initiation, promotion, and progression. The compound has strong antioxidative and anti-inflammatory activities which amy contribute to its chemopreventive/chemoprotective properties. In the present work, we have found that resveratrol reduces viability and DNA synthesis capability of cultured human promyelocytic leukemia (HL-60) cells. Likewise, the viability of human breast cancer cell line, MCF-7 was reduced by resveratrol treatment. The growth inhibitory and antiproliferative properties of resveratrol appear to be associated with its induction of apoptotic cell death as determined by morphological and ultrastructural changes, agarose gel electrphoretic analysis of internucleosomal DNA fragmentation, and in situ terminal end-labeling of fragmented DNA (TUNEL). This compound also inhibited the phorbol ester-induced expression of cyclooxygenase-2 (COX-2) protein in immortalized human mammary epithelial MCF-10A cells. These results suggest that resveratrol has the promising cancer therapeutic/chemopreventive potential.

• Natural Product Sciences
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• 제27권1호
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• pp.49-53
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• 2021

Balanophora laxiflora Hemsl. (Balanophoraceae) is a traditional medicinal plant with a diverse array of biological activities. In our exploration of new bioactive constituents from B. laxiflora, we isolated five compounds, including a new lignan, balanophorone (5), and four known phenolic compounds (1-4). The chemical structures of these compounds were determined by extensive spectroscopic analyses, including 1D and 2D NMR, HR-ESI-MS, and CD. In addition, we evaluated the effects of each of the isolates (1-5) on the messenger RNA expression levels of tumor necrosis factor (TNF)-α and cyclooxygenase (COX)-2 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cells. Compound 2 showed significant inhibition of LPS-induced COX-2 and TNF-α expression in RAW 264.7 macrophages, while compound 4 showed moderate cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cells, with IC50 values of 18.3 and 30.7 µM, respectively. No significant effects on the viability of normal mammary epithelial cells were observed.

• IMMUNE NETWORK
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• 제20권4호
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• pp.33.1-33.19
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• 2020

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both T_H1 and T_H2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces T_H2 and T_H17 responses but reduces T_H1 and T_reg responses regardless of adjuvant type, whereas CFA but not alum increased follicular T_H response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

• BMB Reports
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• 제49권12호
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• pp.651-652
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• 2016

EphA2 has been implicated in amplifying ErbB2 tumorigenic signaling. One protein that interacts with EphA2 is the Anks1a PTB adaptor. However, the precise role of Anks1a in EphA2-mediated tumorigenesis is unclear. We demonstrated that Anks1a localizes to the ER upon phosphorylation and that the Ankyrin repeats and PTB of Anks1a bind to EphA2 and Sec23, respectively. Thus, Anks1a facilitates the selective packaging of EphA2 into COPII vesicles. Additionally, Anks1a knockout mice, a phenocopy of EphA2 knockout mice, exhibited markedly reduced ErbB2-induced breast tumorigenesis. Strikingly, ErbB2 did not localize to the cell surface following Anks1a knockdown in primary mammary tumor cells over-expressing ErbB2. Importantly, EphA2 was critical for stabilizing ErbB2 through complex formation, but its interaction with Anks1a also facilitated ErbB2 loading into COPII carriers. These findings suggest a novel role for Anks1a in the molecular pathogenesis of breast tumors and possibly other human diseases.