• Biomolecules & Therapeutics
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• 제31권5호
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• pp.526-535
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• 2023

Breast cancer is the most common cancer and a frequent cause of cancer-related deaths among women wordlwide. As therapeutic strategies for breast cancer have limitations, novel chemotherapeutic reagents and treatment strategies are needed. In this study, we investigated the anti-cancer effect of synthetic homoisoflavane derivatives of cremastranone on breast cancer cells. Homoisoflavane derivatives, SH-17059 and SH-19021, reduced cell proliferation through G2/M cell cycle arrest and induced caspase-independent cell death. These compounds increased heme oxygenase-1 (HO-1) and 5-aminolevulinic acid synthase 1 (ALAS1), suggesting downregulation of heme. They also induced reactive oxygen species (ROS) generation and lipid peroxidation. Furthermore, they reduced expression of glutathione peroxidase 4 (GPX4). Therefore, we suggest that the SH-17059 and SH-19021 induced the caspase-independent cell death through the accumulation of iron from heme degradation, and the ferroptosis might be one of the potential candidates for caspase-independent cell death.

• 한국임상수의학회지
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• 제21권3호
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• pp.253-258
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• 2004

DNA double-strand break (DSB) is a serious treat for the cells including mutations, chromosome rearrangements, and even cell death if not repaired or misrepaired. Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) bound to double strand DNA breaks are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and the interaction is essential for DNA-dependent protein kinase (DNA-PK) activity. The Ku80 mutants were designed to bind Ku70 but not DNA end binding activity and the peptides were treated in breast cancer cells for co-therapy strategy to see whether the targeted inhibition of DNA-dependent protein kinase (DNA-PK) activity sensitized breast cancer cells to ionizing irradiation or chemotherapy drug to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. We designed domains of Ku80 mutants, 26 residues of amino acids (HN-26) as a control peptide or 38 (HNI-38) residues of amino acids which contain domains of the membrane-translocation hydrophobic signal sequence and the nuclear localization sequence, but HNI-38 has additional twelve residues of peptide inhibitor region. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, resulting in inactivation of DNA-PK complex activity in breast cancer cells (MDA-465 and MDA-468). Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to irradiation or chemotherapy drugs. The growth of breast cancer cells was also inhibited. These results demonstrate the possibility of synthetic peptide to apply breast cancer therapy to induce apoptosis of cancer cells.

• 대한의생명과학회지
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• 제24권1호
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• pp.9-14
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• 2018

Ki-67 has been widely performed and become an important biomarker in worldwide clinics, but the standard cut off value of Ki-67 index in breast cancer is still controversy. The objective study was to understand the Ki-67 in breast cancer subtypes and to investigate relative risk of breast cancer subtypes according to Ki-67 cut off value in Korean breast cancer. Immunohistochemical staining (IHC) for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 index was examined from 123 breast cancer patients. Ki-67 index was significantly overexpressed in PR, ER, and HER2 hormone negative groups. Ki-67 index in Triple negative and HER2 subtypes was shown significantly higher than that in Luminal A and Luminal B subtype. Then, we compared the relative risk of each subtype according to 14% and 20% Ki-67 cut off value, which were applied in most clinics. Especially, 20% Ki-67 cut off value in HER2 and Triple negative subtypes was shown 8.41 fold and 2.83 fold higher relative risk than this in Luminal A subtype. Moreover, Ki-67 index in HER2 2+ or 3+ status showed significantly overexpressed than this in HER2 1+ status. At the 20% Ki-67 cut off value, HER2 1+ or 2+ status and 3+ status showed significant difference. Therefore, the 20% Ki-67 cut off value will be useful as a precise prognostic management and helpful for interpreting diverse outcomes of other subtypes in breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3391-3396
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• 2014

Background: Vitamin D has been suggested as one of the critical factors for female reproductive health with protective activities against different cancers but there are conflicting facts regarding its role on breast cancer without any clear data on premenopausal cases. This study aimed to evaluate the role of vitamin D from dietary sources and sunlight exposure on the incidence of premenopausal breast cancer. Materials and Methods: We conducted a case control study on 60 newly diagnosed premenopausal breast cancer patients and 116 normal women who lived in Sabzevar and surrounding villages in Razavi, Khorasan, a rural and conservative area of Iran. Results: The mean concentrations of 25-OH vitamin D in cases and controls were $15.2{\pm}8.15$ vs $15.5{\pm}7/45ng/ml$, both well below normal values elsewhere. In fact 50% of analyzed individuals showed very severe or severe vitamin D deficiency and the rest (25%) were detected in suboptimal levels. Although the lack of vitamin D and calcium supplementation increased slightly the risk of premenopausal breast cancer (p=0.009, OR=1.115, CI 95%=1.049-1.187), higher prevalence of weekly egg consumption (86.66% vs 96.55%, p=0.023, OR=0.232, CI 95% 0.065-0.806) showed a slight protective role. The last but the most important risk factor was lack of sunlight exposure because the breast cancer patients had total body coverage from sun (p=0.007, OR=10.131, CI 98% 0.314-78.102). Conclusion: This study pointed out the role of vitamin D and other possible risk factors on the development and growth of breast tumors in this special geographical region. Although this study has revealed the interactions between hormonal and environmental factors in this province of Iran, understanding the deficiency pattern and its contribution to other lifestyle factors elsewhere is also necessary.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5307-5312
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• 2012

Introduction: Breast cancer cells and tumor stroma produce different cytokines and soluble factors. Cytokines, while playing crucial roles in immune responses to tumors, also favour tumor growth and progression. IL-7 and G-CSF are two cytokines that may exert influences on the pathophysiology of breast cancer. Materials and Methods: Sera were collected from 136 females with breast cancer before receiving chemotherapy or radiotherapy. The control group comprised of 60 healthy age-matched females without any acute or chronic diseases with no family history of breast cancer. Serum levels of IL-7 and G-CSF were measured by commercial enzyme linked immunosorbent assay. Results: While there was no significant difference in the level of G-CSF between patients ($92.81{\pm}594.54$ pg/ml) and controls (0.00 pg/ml), G-CSF level in sera of patients with advanced stages of breast cancer was elevated compared to early stages (p=0.0001). Moreover, the highest level of G-CSF was seen in patients with N3 phase tumors (p=0.0001). IL-7 was slightly but not significantly higher in the control group ($0.04{\pm}0.11$ pg/ml) in comparison with patients ($0.02{\pm}0.10$ pg/ml). Interestingly, a significant increase in the level of IL-7 in patients with skin involvement was observed (p=0.001). Conclusion: Our results showed an elevation of G-CSF in sera of patients with advanced stages of tumor, while IL-7 elevation correlated with skin involvement of breast cancer. IL-7 can be produced by keratinocytes in skin tissue and may be involved in the pathologic establishment of metastatic tumor cells in skin.

• 동아시아식생활학회지
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• 제15권4호
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• pp.397-404
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• 2005

The propose of this study was to investigate taurine intake in formula-fed and breast-fed infants and to estimate the level of taurine of blood and urine in order to determine the requirement of taurine intake in infants. These results will be useful to suggest the guideline of requirement of taurine intake and may contribute toward the proper use of breast milk substitutes. Experimental groups were breast-fed infants (n=10) and formula-fed infants (n=10) of 20 normal delivery infants in general hospital. This study was longitudinal study from birth up to 16weeks (0 week, 4 weeks, 8 weeks, 12 weeks, 16 weeks). The items of test were anthropometry(weight, height, head circumference, chest circumference), intake of taurine, taurine level of blood and urine in breast-fed and formula-fed infants. There were no significant differences between breast-fed and formula-fed infants in weight, height, head and chest circumference. There is a need for future studies of exclusive infants with larger samples to determine which growth pattern should be considered as the norm. Taurine concentration of plasma and urine did not differ between breast-fed and formula-fed infants. Taurine intake recommendations for infants is about 30mg/day from this study. This data will be useful for production of human-like formula milk and suggestion of an index of selection of a consumer in taurine.

• Biomolecules & Therapeutics
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• 제20권3호
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• pp.313-319
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• 2012

In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.

• 한국미생물·생명공학회지
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• 제21권6호
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• pp.594-599
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• 1993

In the course of screening for microbial metabolites employing human cancer cell line, we identified a mycelial extract of Streptomyces sp. 1365, which are effective on growth inhibition and morphological change of MCF-7, human breasr cancer cell line. By repeased column chromatography and recrystallization process, yellow needle crystals were obtained as an active compound and identified as resistomycin by spectral analysis.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.142-142
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• 2002

Many studies have identified the phosphatidylinositol 3-kinase (PI3K) as a key regulator for various cellular functions including cell survival, growth and motility. We have previously shown that H-ras, but not N-ras, induces invasiveness and motility in human breast epithelial cells (MCF10A), while both H-ras and N-ras induce transformed phenotype.(omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.109.2-110
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• 2003

Estrogen is the most important endocrine hormone that has reproduction and physiological process in a number of tissues. However, an excess of estrogen can promotes the growth of hormone-dependent breast cancer. Thus the regulation of estrogen level is important a prevention of estrogen-related cancer. It has been reported that some of flavonoids could inhibit estrogen-dependent cancer. And these compounds are expected as chemopreventive agents on estrogen related disease. (omitted)