ArticleJournal of Cancer2011
Effects of an Indolocarbazole-Derived CDK4 Inhibitor on Breast Cancer Cells.
Article in Journal of Cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Updating mRNA variants of the human RSK4 gene and their expression in different stressed situations.Heliyon · 2024Article
- Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy.Scientific reports · 2021Article
- Article
- Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells.Scientific reports · 2018Article
- Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor β1 induction.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Article
- The other side of the coin: the tumor-suppressive aspect of oncogenes and the oncogenic aspect of tumor-suppressive genes, such as those along the CCND-CDK4/6-RB axis.Cell cycle (Georgetown, Tex.) · 2014Review
- Cyclin-dependent kinase 4 may be expressed as multiple proteins and have functions that are independent of binding to CCND and RB and occur at the S and G 2/M phases of the cell cycle.Cell cycle (Georgetown, Tex.) · 2013Article
- Basic anatomy and tumor biology of the RPS6KA6 gene that encodes the p90 ribosomal S6 kinase-4.Oncogene · 2013Article
- CyclinD1 protein plays different roles in modulating chemoresponses in MCF7 and MDA-MB231 cells.Journal of carcinogenesis · 2012Article
- Revealing the anti-tumor effect of artificial miRNA p-27-5p on human breast carcinoma cell line T-47D.International journal of molecular sciences · 2012Article
- Cyclin D1 inhibits whereas c-Myc enhances the cytotoxicity of cisplatin in mouse pancreatic cancer cells via regulation of several members of the NF-κB and Bcl-2 families.Journal of carcinogenesis · 2011Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
introductionCyclin D1 (D1) binds to cyclin-dependent kinases (CDK) 4 or 6 to form a holoenzyme that phosphorylates the Rb protein to promote cell cycle progression from G1 to S phase. Therefore, targeting CDK4/6 may be a good strategy for chemotherapy of cancer. We performed a proof-of-principle study to determine the effect of Naphtho [2, 1-α] pyrrolo [3, 4-c] carbazole-5, 7 (6H, 12H)-dione (NPCD), a novel CDK4 inhibitor, on breast cancer cell lines.
methodsNPCD was synthesized and purified to over 99% purity verified by HPLC. MCF7, MB231, MCF15, T47D and GI101Ap human breast cancer cells were analyzed for the efficacy of NPCD with MTT and clonogenic assays, with FACS and staining for ethidium bromide and acridine orange for cell death and cell cycle profile. Western blot, reverse transcription and PCR were used for studies of gene expression, and co-immunoprecipitation for protein-complex formation.
resultsMTT assay showed that NPCD caused growth arrest and apoptosis of MCF7, MDA-MB231, T47D, MCF15 and GI101Ap cells with an IC50 ranging between 3 to 8 µM given as a single dose. The growth arrest persisted for many days after cessation of the treatment, as shown in a clonogenic assay. NPCD could induce or reduce the D1 and CDK4 protein levels, depending on the cell line, but this effect was not correlated with its efficacy. Phosphorylation of D1 at Thr286 was decreased but it unexpectedly did not correlate with the change in D1 level in the cell lines studied. Phosphorylation of the Rb protein was decreased as expected whereas the p27kip1 protein level was decreased unexpectedly. Protein levels of p21cip1, CDK2 and cyclin E were also decreased in some, but not all, of the cell lines, whereas the mRNA levels of D1, CDK4, cyclin E, CDK2, p27kip1 and p21cip1 were increased in different cell lines.
conclusionsNPCD can cause long-lasting growth arrest and cell death of breast cancer cell lines at an IC50 of 3-8 µM. Decreased phosphorylation of Rb by D1-CDK4/6 and decreased p27kip1 protein level may be part of the underlying mechanism.
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