Dataset Information

BC-N102 suppress breast cancer tumorigenesis by interfering with cell cycle regulatory proteins and hormonal signaling, and induction of time-course arrest of cell cycle at G1/G0 phase.

ABSTRACT: Mechanisms of breast cancer progression and invasion, often involve alteration of hormonal signaling, and upregulation and/or activation of signal transduction pathways that input to cell cycle regulation. Herein, we describe a rationally designed first-in-class novel small molecule inhibitor for targeting oncogenic and hormonal signaling in ER-positive breast cancer. BC-N102 treatment exhibits dose-dependent cytotoxic effects against ER+ breast cancer cell lines. BC-N102 exhibited time course- and dose-dependent cell cycle arrest via downregulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-Akt, CDK2, and CDK4 while increasing p38 mitogen-activated protein kinase (MAPK), and mineralocorticoid receptor (MR) signaling in breast cancer cell line. In addition, we found that BC-N102 suppressed breast cancer tumorigenesis in vivo and prolonged the survival of animals. Our results suggest that the proper application of BC-N102 may be a beneficial chemotherapeutic strategy for ER+ breast cancer patients.

SUBMITTER: Lawal B

PROVIDER: S-EPMC8375223 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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BC-N102 suppress breast cancer tumorigenesis by interfering with cell cycle regulatory proteins and hormonal signaling, and induction of time-course arrest of cell cycle at G1/G0 phase.

Lawal Bashir B Kuo Yu-Cheng YC Wu Alexander T H ATH Huang Hsu-Shan HS

International journal of biological sciences 20210725 12

Mechanisms of breast cancer progression and invasion, often involve alteration of hormonal signaling, and upregulation and/or activation of signal transduction pathways that input to cell cycle regulation<b>.</b> Herein, we describe a rationally designed first-in-class novel small molecule inhibitor for targeting oncogenic and hormonal signaling in ER-positive breast cancer. BC-N102 treatment exhibits dose-dependent cytotoxic effects against ER+ breast cancer cell lines. BC-N102 exhibited time c ...[more]

PMID: 34421361

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Project description:UnlabelledMany viruses replicate most efficiently in specific phases of the cell cycle, establishing or exploiting favorable conditions for viral replication, although little is known about the relationship between caliciviruses and the cell cycle. Microarray and Western blot analysis of murine norovirus 1 (MNV-1)-infected cells showed changes in cyclin transcript and protein levels indicative of a G1 phase arrest. Cell cycle analysis confirmed that MNV-1 infection caused a prolonging of the G1 phase and an accumulation of cells in the G0/G1 phase. The accumulation in G0/G1 phase was caused by a reduction in cell cycle progression through the G1/S restriction point, with MNV-1-infected cells released from a G1 arrest showing reduced cell cycle progression compared to mock-infected cells. MNV-1 replication was compared in populations of cells synchronized into specific cell cycle phases and in asynchronously growing cells. Cells actively progressing through the G1 phase had a 2-fold or higher increase in virus progeny and capsid protein expression over cells in other phases of the cell cycle or in unsynchronized populations. These findings suggest that MNV-1 infection leads to prolonging of the G1 phase and a reduction in S phase entry in host cells, establishing favorable conditions for viral protein production and viral replication. There is limited information on the interactions between noroviruses and the cell cycle, and this observation of increased replication in the G1 phase may be representative of other members of the Caliciviridae.ImportanceNoroviruses have proven recalcitrant to growth in cell culture, limiting our understanding of the interaction between these viruses and the infected cell. In this study, we used the cell-culturable MNV-1 to show that infection of murine macrophages affects the G1/S cell cycle phase transition, leading to an arrest in cell cycle progression and an accumulation of cells in the G0/G1 phase. Furthermore, we show that MNV replication is enhanced in the G1 phase compared to other stages of the cell cycle. Manipulating the cell cycle or adapting to cell cycle responses of the host cell is a mechanism to enhance virus replication. To the best of our knowledge, this is the first report of a norovirus interacting with the host cell cycle and exploiting the favorable conditions of the G0/G1 phase for RNA virus replication.

Project description:BackgroundMultiple myeloma (MM) is a B-lymphocyte-derived malignancy. It ranks as the second most common hematological malignancy, with relatively high morbidity and mortality. However, the molecular mechanisms of MM occurrence and development remain elusive. This study found that long non-coding RNA AL928768.3 (lncRNA AL) was abnormally expressed in MM samples. However, the effect and molecular mechanism of lncRNA AL on the occurrence and development of MM remains unclear.MethodsBone marrow fluids of MM patients (n=54) and volunteers (n=13) were collected and CD138+ cells were isolated. The expression level of lncRNA AL in MM cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of lncRNA AL and the clinicopathological features of patients was analyzed. Lentiviral vectors targeting lncRNA AL knockdown were constructed and transfected into cells. After transfection, the effects of lncRNA AL knockdown on MM cell proliferation and the cell cycle were detected by the CCK-8 assay, clone formation assay, and flow cytometry. The effect of lncRNA AL knockdown on MM cell cycle-related proteins was detected by Western blot. In addition, tumorigenicity experiments were performed in nude mice to detect the effect of lncRNA AL knockdown on MM cell proliferation in vivo.ResultsLncRNA AL was highly expressed in MM patient samples and cell lines, and was significantly correlated with the disease stage of patients. Knockdown of lncRNA AL significantly inhibited the proliferation and colony formation of MM cells and induced cell cycle arrest in G0/G1 phase. Western blot analysis showed that knockdown of lncRNA AL significantly inhibited the expression of CDK2 and cyclin D1 and promoted the expression of cyclin suppressor p21. Knockdown of lncRNA AL significantly inhibited the proliferation of MM cells in nude mice.ConclusionsLncRNA AL was highly expressed in MM patients. Knockdown of this gene significantly inhibited the proliferative ability of MM cells and induced cell cycle arrest in G0/G1 phase. Therefore, lncRNA AL may be a novel biological target molecule for the early diagnosis, treatment, and prognostic evaluation of MM patients.

Dataset Information

BC-N102 suppress breast cancer tumorigenesis by interfering with cell cycle regulatory proteins and hormonal signaling, and induction of time-course arrest of cell cycle at G1/G0 phase.

Publications

BC-N102 suppress breast cancer tumorigenesis by interfering with cell cycle regulatory proteins and hormonal signaling, and induction of time-course arrest of cell cycle at G1/G0 phase.

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