Mechanisms of resistance to cyclin-dependent kinase 4/6 inhibitors

Molecular Biology Reports, Journal Year: 2021, Volume and Issue: 48(1), P. 915 - 925

Published: Jan. 1, 2021

Language: Английский

---

Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells

Cancers, Journal Year: 2021, Volume and Issue: 13(22), P. 5741 - 5741

Published: Nov. 16, 2021

Cannabinoid receptors, which are widely distributed in the body, have been considered as possible pharmacological targets for management of several tumors. type 2 receptors (CB2Rs) belong to G protein-coupled receptor family and mainly expressed hematopoietic immune cells, such B-cells, T-cells, macrophages; thus, CB2R activation might be useful treating cancers affecting plasma multiple myeloma (MM). Previous studies shown that stimulation may anti-proliferative effects; therefore, purpose present study was explore antitumor effect beta-caryophyllene (BCP), a agonist, an vitro model MM. Dexamethasone-resistant (MM.1R) sensitive (MM.1S) human cell lines were used this study. Cells treated with different concentrations BCP 24 h, group cells pre-incubated AM630, specific antagonist. treatment reduced proliferation through stimulation; notably, considerably increased pro-apoptotic protein Bax decreased anti-apoptotic molecule Bcl-2. Furthermore, increase caspase 3 levels detected following incubation, thus demonstrating its apoptosis activation. In addition, regulated AKT, Wnt1, beta-catenin expression, showing decrease cancer by modulating Wnt/β-catenin signaling. These effects counteracted AM630 co-incubation, confirming BCP's mechanism action is related modulation. A β-catenin impaired cycle especially promoted cyclin D1 CDK 4/6 reduction. Taken together, these data revealed significant effective anti-cancer MM activating apoptosis, molecular pathways, downregulating cycle.

Language: Английский

---

Prognostic Potential of Cyclin D1 Expression in Colorectal Cancer

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(2), P. 572 - 572

Published: Jan. 10, 2023

Cyclin D1 is mainly known as an oncogenic driver in cancers, and the dysregulated cyclin D1/cyclin-dependent kinase (CDK) 4/6 axis considered attractive target for cancer therapy. Recent studies have reported that tumors respond to therapeutic interventions targeting altered expression via application of CDK4/6 inhibitor. However, prognostic contributions colorectal (CRC) remain controversial. Herein, we assessed associations between clinicopathological factors, including patients' overall survival (OS) recurrence-free (RFS), 495 surgically resected primary CRCs. We also examined previous High expressions (cyclin D1High) was observed 389 CRC cases (78.6%). D1High consistently predicted better patient OS RFS Based on multivariate analysis, young age patients remained independent prognosticators higher rate, whereas D1High, females, chemotherapy, absence nodal metastasis, lower T-category RFS. commonly overexpressed CRCs, its can be used a favorable indicator with CRCs; this may important predicting responses subsequent inhibitors.

Language: Английский

---

Mellitin peptide quantification in seasonally collected crude bee venom and its anticancer effects on myelogenous K562 human leukaemia cell line

BMC Complementary Medicine and Therapies, Journal Year: 2023, Volume and Issue: 23(1)

Published: April 25, 2023

Abstract Background Apitherapy is an emerging field in cancer research, particularly developing communities. The potency of Melittin (MEL), a major constituent bee venom accounted for the cytotoxic capacity against cells. It postulated that genotype bees and time collection influences its specific activity certain types cancer. Method Hereby, Jordanian crude (JCBV) was collected during different seasons year, specifically spring, summer autumn investigated vitro antitumour effects. Venom springtime comprised highest quantity MEL comparison to some other time. Springtime-collected JCBV extract were tested on immortal myelogenous leukaemia cell line, namely K562 leukemic Treated cells examined modality via flow cytometry analysis death mediating gene expressions. Results showed IC 50 3.7 ± 0.37 μg/ml 1.84 0.75 μg/ml, respectively. In positive control, MEL-treated exhibited late apoptotic with moderate cellular arrest at G0/G1 increase number G2/M phase. Expression NF-κB/MAPK14 axis inhibited JCBV-treated cells, as well expression c-MYC CDK4. Moreover, marked upregulation ABL1, JUN TNF observed. conclusion, springtime-collected content while both pure apoptotic, necrotic, cycle efficiency Conclusion Integration chemotherapy needs more investigation should be carefully translated into clinical use. During such translation, correlation genotype, concentration CBV profiled.

Language: Английский

---

Deciphering the Immunomodulatory Role of Cyclin-Dependent Kinase 4/6 Inhibitors in the Tumor Microenvironment

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2236 - 2236

Published: Jan. 23, 2023

Cancer is characterized by persistent cell proliferation driven aberrant cycle regulation and stimulation of cyclin-dependent kinases (CDKs). A very intriguing potential approach for the development antitumor medicines suppression CDKs that lead to induction apoptosis arrest. The shift from G0/G1 phase S phase, which active transcription synthesis, depends on cyclin D-CDK4/6 complex. precise balance between anticancer activity general toxicity demonstrated CDK inhibitors, can specifically block CDK4/6 control reducing G1 transition. inhibitors have recently been reported exhibit significant growth inhibition via modulating tumour microenvironment in cancerous cells. One new understanding these serve important functions interaction among cells host immune system addition being cytostatic. Herein, we discuss biological significance cancer therapeutics, as well their impact T other Furthermore, explore integration preclinical findings pharmaceuticals' ability enhance immunity.

Language: Английский

---