Selective CDK4/6 inhibition of novel 1,2,3-triazole tethered acridinedione derivatives induces G1/S cell cycle transition arrest via Rb phosphorylation blockade in breast cancer models

Bioorg Chem. 2021 Nov;116:105377. doi: 10.1016/j.bioorg.2021.105377. Epub 2021 Sep 17.ABSTRACTCDK4 &CDK6 are essential regulators of initial cell cycle phases and are always considered an exciting choice for anti-cancer therapy. In the present study, we presented the structure-based rational design &synthesis of a new class of 1,2,3-triazole tethered acridinedione derivatives (6a-l) as selective CDK4/6 inhibitors. Title molecules were prepared as a result of the rate-determining reaction between substituted derivatives of 1-Phenyl-1H-1,2,3-triazole-4-carbaldehydes and substituted dimedones, and the molecules were structurally characterized by IR, 1H,13C NMR, and MS spectral data. All molecules were screened for in-vitro cytotoxic potential against a group of human breast tumor cell lines of distinct origin with differential Rb expression status. Out of entire series of conjugated hexahydro acridinediones, 6g showed potent cytotoxic effect against MCF-7, BT-474, and SK-BR3 cell lines with IC50values 0.173 ± 0.037, 0.117 ± 0.025, and 0.136 ± 0.027 μM, respectively. Further, CDK inhibition assays revealed that the compounds 6g and 6h selectively inhibit CDK4/6 over other CDK-parter complexes of the family against the selected cell line group except for MDA-MB468 cells. Furthermore, apoptotic evaluation and cell cycle analysis determined that compound 6g successfully triggered apoptosis in all examined cell lines except MDA-MB468 through blocking G...
Source: Bioorganic Chemistry - Category: Chemistry Authors: Source Type: research

Related Links:

Although breast cancer has been previously considered “cold” tumors, numerous studies are currently conducted to explore the great potentials of immunotherapies in improving breast cancer patient outcomes. In addition to the focus on stimulating adaptive immunity for antitumor responses, growing evidence showed the importance of triggering host innate immunity to eradicate established tumors and/or control tumor metastasis of breast cancer. In this review, we first briefly introduce the breast tumor immune microenvironment. We also discuss innate immune targets and pathways and mechanisms of their synergy with ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
CONCLUSION: The above-combined results revealed the anticancer effect of CVLME, which may be due to the selective induction of ROS in breast carcinoma.
Source: Indian Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research
-liang Ye Folate-aminocaproic acid-doxorubicin (FA-AMA-hyd-DOX) was firstly synthesized by our group. It was indicated that FA-AMA-hyd-DOX was pH-responsive, and had strong cytotoxicity on a folate receptor overexpressing cell line (KB cells) in vitro. The aim of our study was to further explore the potential use of FA-AMA-hyd-DOX as a new therapeutic drug for breast cancer. The cellular uptake and the antiproliferative activity of the FA-AMA-hyd-DOX in MDA-MB-231 cells were measured. Compared with DOX, FA-AMA-hyd-DOX exhibited higher targeting ability and cytotoxicity to FR-positive tumor cells. Subsequently, the tiss...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
This study aims to investigate the long-term risk of a SPM attributable to the radiation therapy in patients with the initial lung cancer.METHODS: Patients initially diagnosed with lung cancer between January 1975 and November 2011 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. SPM was defined as the occurrence of a second cancer at least five years after the diagnosis of the initial lung cancer. Age- and propensity score matching (PSM)-adjusted competing risk analyses were performed to compare the risk of SPM.RESULTS: Of 47,911 patients, 9,162 (19.1%) underwent radiotherapy for the i...
Source: Journal of Thoracic Disease - Category: Respiratory Medicine Authors: Source Type: research
ACS Applied Materials&InterfacesDOI: 10.1021/acsami.1c18053
Source: ACS Applied Materials and Interfaces - Category: Materials Science Authors: Source Type: research
ACS Applied Materials&InterfacesDOI: 10.1021/acsami.1c16366
Source: ACS Applied Materials and Interfaces - Category: Materials Science Authors: Source Type: research
CONCLUSIONS: These findings provide new insight into the mechanism underlying the inhibitory effects of TAD1822-7 via ERβ-mediated pathways in breast cancer cells.PMID:34792729 | DOI:10.1007/s11033-021-06950-5
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Source Type: research
Obstet Gynecol. 2021 Dec 1;138(6):950-960. doi: 10.1097/AOG.0000000000004601.ABSTRACTWith an estimated 3.8 million breast cancer survivors in the United States, obstetrician-gynecologists often are on the front lines of addressing survivorship issues, including the hypoestrogenic-related adverse effects of cancer therapies or early menopause in survivors (1). Although systemic and vaginal estrogen are used widely for symptomatic relief of genitourinary syndrome of menopause in the general population, among individuals with a history of hormone-sensitive cancer, there is uncertainty about the safety of hormone-based therapy...
Source: Obstetrics and Gynecology - Category: OBGYN Source Type: research
CONCLUSIONS: These findings provide new insight into the mechanism underlying the inhibitory effects of TAD1822-7 via ERβ-mediated pathways in breast cancer cells.PMID:34792729 | DOI:10.1007/s11033-021-06950-5
Source: Mol Biol Cell - Category: Molecular Biology Authors: Source Type: research
Obstet Gynecol. 2021 Dec 1;138(6):950-960. doi: 10.1097/AOG.0000000000004601.ABSTRACTWith an estimated 3.8 million breast cancer survivors in the United States, obstetrician-gynecologists often are on the front lines of addressing survivorship issues, including the hypoestrogenic-related adverse effects of cancer therapies or early menopause in survivors (1). Although systemic and vaginal estrogen are used widely for symptomatic relief of genitourinary syndrome of menopause in the general population, among individuals with a history of hormone-sensitive cancer, there is uncertainty about the safety of hormone-based therapy...
Source: Obstetrics and Gynecology - Category: OBGYN Source Type: research
More News: Breast Cancer | Cancer | Cancer & Oncology | Cancer Therapy | Chemistry | Study