MyMedR

Displaying all 4 publications

Abstract:

Sort:

Black soybean extract inhibits rat mammary carcinogenesis through BRCA1 and TNF-α expression: In silico and in vivo study

Pratama DAO, Fernanda A, Raissa R, Permata FS, Nordin ML

Open Vet J, 2024 Oct;14(10):2678-2686.
PMID: 39545186 DOI: 10.5455/OVJ.2024.v14.i10.17

BACKGROUND: Mammary gland carcinoma is a malignant type of cancer that occurs in mammae tissue. Dimethylbenzene (α) anthracene (DMBA) is a carcinogenic agent that causes mammary cancer by damaging cellular DNA. Flavonoids found in the black soybean (Glycine max L. Merr) exhibit anti-carcinogenic effects.
AIM: This study evaluated the anticarcinogenic effects of black soybean extract.
METHODS: The activity of flavonoid compounds in black soybean was determined in silico. Five groups of rats, four in each group, were established, consisting of a negative control, a positive control, and three treatment groups. Treatment included black soybean extract administration (i.e., T1 = 200, T2 = 400, and T3 = 800 mg of black soybean extract/kg body weight for 10 days). The observed parameters included the immunohistochemical analysis of Breast Cancer 1(BRCA1) and TNF-α.
RESULTS: Based on an in silico study, compounds from black soybeans are non-toxic. Functional annotation analysis revealed that most of the target proteins have a role in biological processes associated with cancer development. An in vivo analysis using an animal mammae cancer model indicated that black soybean extracts inhibited mammae cancer progression by attenuating TNF-α and BRCA1 expression.
CONCLUSION: The most effective dosage of black soybean extract was 200 mg/kg body weight. An increase in BRCA1 and TNF-α expression may be related to the effects of catechin, daidzein, genistein, and glycitein, which are present in black soybeans.

Matched MeSH terms: BRCA1 Protein/metabolism
Retarding breast tumor growth with nanoparticle-facilitated intravenous delivery of BRCA1 and BRCA2 tumor suppressor genes

Ibnat N, Chowdhury EH

Sci Rep, 2023 Jan 11;13(1):536.
PMID: 36631481 DOI: 10.1038/s41598-022-25511-9

Gene augmentation therapy entails replacement of the abnormal tumor suppressor genes in cancer cells. In this study, we performed gene augmentation for BRCA1/2 tumor suppressors in order to retard tumor development in breast cancer mouse model. We formulated inorganic carbonate apatite (CA) nanoparticles (NPs) to carry and deliver the purified BRCA1/2 gene- bearing plasmid DNA both in vitro and in vivo. The outcome of BRCA1/2 plasmid-loaded NPs delivery on cellular viability of three breast cancer cell lines such as MCF-7, MDA-MB-231 and 4T1 were evaluated by MTT assay. The result in MCF-7 cell line exhibited that transfection of BRCA 1/2 plasmids with CA NPs significantly reduced cancer cell growth in comparison to control group. Moreover, we noticed a likely pattern of cellular cytotoxicity in 4T1 murine cancer cell line. Following transfection with BRCA1 plasmid-loaded NPs, and Western blot analysis, a notable reduction in the phospho-MAPK protein of MAPK signaling pathway was detected, revealing reduced growth signal. Furthermore, in vivo study in 4T1 induced breast cancer mouse model showed that the tumor growth rate and final volume were decreased significantly in the mouse group treated intravenously with BRCA1 + NPs and BRCA2 + NPs formulations. Our results established that BRCA1/2 plasmids incorporated into CA NPs mitigated breast tumor growth, signifying their application in the therapy for breast cancer.

Matched MeSH terms: BRCA1 Protein/metabolism
KSR1 regulates BRCA1 degradation and inhibits breast cancer growth

Stebbing J, Zhang H, Xu Y, Lit LC, Green AR, Grothey A, et al.

Oncogene, 2015 Apr 16;34(16):2103-14.
PMID: 24909178 DOI: 10.1038/onc.2014.129

Kinase suppressor of Ras-1 (KSR1) facilitates signal transduction in Ras-dependent cancers, including pancreatic and lung carcinomas but its role in breast cancer has not been well studied. Here, we demonstrate for the first time it functions as a tumor suppressor in breast cancer in contrast to data in other tumors. Breast cancer patients (n>1000) with high KSR1 showed better disease-free and overall survival, results also supported by Oncomine analyses, microarray data (n=2878) and genomic data from paired tumor and cell-free DNA samples revealing loss of heterozygosity. KSR1 expression is associated with high breast cancer 1, early onset (BRCA1), high BRCA1-associated ring domain 1 (BARD1) and checkpoint kinase 1 (Chk1) levels. Phospho-profiling of major components of the canonical Ras-RAF-mitogen-activated protein kinases pathway showed no significant changes after KSR1 overexpression or silencing. Moreover, KSR1 stably transfected cells formed fewer and smaller size colonies compared to the parental ones, while in vivo mouse model also demonstrated that the growth of xenograft tumors overexpressing KSR1 was inhibited. The tumor suppressive action of KSR1 is BRCA1 dependent shown by 3D-matrigel and soft agar assays. KSR1 stabilizes BRCA1 protein levels by reducing BRCA1 ubiquitination through increasing BARD1 abundance. These data link these proteins in a continuum with clinical relevance and position KSR1 in the major oncoprotein pathways in breast tumorigenesis.

Matched MeSH terms: BRCA1 Protein/metabolism*
Fulltext A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition

Gill MR, Harun SN, Halder S, Boghozian RA, Ramadan K, Ahmad H, et al.

Sci Rep, 2016 08 25;6:31973.
PMID: 27558808 DOI: 10.1038/srep31973

Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)2(PIP)](2+) (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (γ-H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)](2+) before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing.

Matched MeSH terms: BRCA1 Protein/metabolism