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Potential anti-gastric cancer properties of modified Lichong decoction based on metabolomics, network pharmacology, and pharmacological verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Lichong decoction, a classic Chinese herbal formula, has been used to treat gynaecological diseases and abdo … oxO3a, decreased the gene expression of FoxO3a, decreased the gene and protein expression of Bcl-2, Cyclin B1 and CDK1, and increased the expression of Bim and Bax in subcutaneously xenografted tumours of nude mice. MLCD had little effect on the levels of ALT, AST, Cr, and BUN, as well as the body weight and indices of the liver, kidney, and spleen in cance …

Tiliacora racemosa leaves induce oxidative stress mediated DNA damage leading to G2/M phase arrest and apoptosis in cervical cancer cells SiHa.

ETHNOPHARMACOLOGICAL RELEVANCE: The Menispermaceae plant Tiliacora racemosa is immensely popular in Indian traditional Ayurvedic medicine as … ion and Parp-1 activation leading to ATM-Chk2-p53 pathway arresting the cells at G2/M-phase through cyclin B1 inhibition. The mitochondrial membrane potential was also disturbed leading to caspase-3 dependent apoptotic induction by both extrinsic and intrinsic pathway. Immunoblots show TRM also inhibited PI3K/Akt and NFκB pathway. NAC pre-treatment rescued …

Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells.

BACKGROUND: HTLV-I is associated with the development of an aggressive form of lymphocytic leukemia known as adult T-cell leukemia/lymphoma (ATLL). A major obstacle for effective treatment of ATLL resides in the genetic diversity of tumor cells and their ability to acquire resistance to chemotherapy regimens. As a result, most patients relapse and current therapeutic approaches still have limited long-term survival benefits. Hence, the development of novel approaches is greatly needed. METHODS: In this study, we found that a small molecule inhibitor of poly (ADP-ribose) polymerase (PARP), PJ-

Root extract of Hemsleya amabilis Diels suppresses renal cell carcinoma cell growth through inducing apoptosis and G2/M phase arrest via PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hemsleya amabilis Diels, belongs to cucurbitaceae, was traditional Chinese medicine (TCM). It is widely used to treat various diseases. However, these diseases may contribute to the development of RCC. AIM OF THE STUDY: investigated the anticancer activities of root extract of Hemsleya amabilis Diels (HRE), and elucidated the underlying molecular mechanism in vivo and in vitro. MATERIALS AND METHODS: Dried Hemsleya amabilis Diels roots were extracted by ethyl acetate and used to treat RCC4, OS-RC-2 and ACHN cells. UHPLC-MS was used to analyze the chemical comp

FBXO43 variants in patients with female infertility characterized by early embryonic arrest.

STUDY QUESTION: Can any new genetic factors responsible for early embryonic arrest in infertile patients be identified, together with the me … ozygous variants reduced the protein level of FBXO43 and reduced the level of its downstream target Cyclin B1 in HEK293T cells. In addition, the variants reduced the ability of exogenous human FBXO43 to rescue the parthenogenetic activation phenotype in Fbxo43 knockdown mouse oocytes. LIMITATIONS, REASONS FOR CAUTION: Owing to the lack of in vivo data from …

Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer.

The HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1) is approved for the treatment of metastatic, HER2-positive breast cancer after prior trastuzumab and taxane therapy, and has also demonstrated efficacy in the adjuvant setting in incomplete responders to neoadjuvant therapy. Despite its objective activity, intrinsic and acquired resistance to T-DM1 remains a major clinical challenge. T-DM1 mediates its activity in a number of ways, encompassing HER2 signalling blockade, Fc-mediated immune response and payload-mediated microtubule poisoning. Resistance mechanisms relating t

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… Despite a defective mitotic spindle, reduced induction of cyclin B1/CDK1 results in an inability to halt cell-cycle progression, consequently leading to mitotic exit and cytokinesis, and thus avoidance of mitotic catastrophe. … B1 expression, but in resistant clones of the same cell lines, no increase in cyclin B1 expression or CDK1 activity was observed, with minimal G 2 /M phase arrest and attenuation of mitotic catastrophe and apoptosis. 27 , 30 Knockdown of CDC20 to promote cyclin B1 expression increased the sensitivity …

A novel dual HDAC and HSP90 inhibitor, MPT0G449, downregulates oncogenic pathways in human acute leukemia in vitro and in vivo.

Acute leukemia is a highly heterogeneous disease; therefore, combination therapy is commonly used for patient treatment. Drug-drug interaction is a major concern of combined therapy; hence, dual/multi-target inhibitors have become a dominant approach for cancer drug development. HDACs and HSP90 are involved in the activation of various oncogenic signaling pathways, including PI3K/AKT/mTOR, JAK/STAT, and RAF/MEK/ERK, which are also highly enriched in acute leukemia gene expression profiles. Therefore, we suggest that dual HDAC and HSP90 inhibitors could represent a novel therapeutic approach fo

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… Cdk1/cdc2 (Try15) is an inhibitory protein that cannot interact with cyclin B1 to promote cell progression from G 2 to M phase 40 . … C The whole-cell lysate was collected for mitotic regulatory proteins, cdk1/cdc2, cyclin B1, PLK, MPM-2, and aurora A, detection by western blotting. …

CS-6-induced p62 accumulation exacerbates DNA damage in colorectal cancer.

BACKGROUND: Gamabufotalin (CS-6), a bufadienolide derived from Chansu, has been reported to exhibit anti-tumor effects in various cancers, including glioblastoma, nonsmall cell lung cancer, and breast cancer. However,its role in colorectal cancer (CRC) remains unexplored. OBJECTIVE: Our study aimed to evaluate the inhibition of CS-6 to CRC cells by cell viability assay, colony formation assay, comet assay, and cell cycle analysis firstly. And its molecular mechanism was studied by immunofluorescence (IF) assay, western blot (WB) assay, siRNA transfection, protein-protein interaction (PPI) net

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… The results indicated that CS-6 treatment led to a reduction in the expression levels of cyclin B1 and CDK1 relative to the control treatment in SW620 and DLD1 cells. … CDK1-cyclin-B1-induced kindlin degradation drives focal adhesion disassembly at mitotic entry . Nat. Cell Biol. 24 , 723 – 736 . 10.1038/s41556-022-00886-z 35469017 PMC9106588 Ciechomska I. A. ( 2018 ). …

Antimitotic drugs in the treatment of cancer.

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell res

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… Since an increase in resistance due to hypoxia in the presence of paclitaxel is reversed by increased cyclin B1 levels, hypoxia reduces the antimitotic activity of paclitaxel by downregulation of cyclin B1 [ 100 ]. … Control of mitosis by changes in the subcellular location of cyclin-B1–Cdk1 and Cdc25C. Curr Opin Cell Biol. 2000;12:658–665. doi: 10.1016/S0955-0674(00)00149-6. 31. Musacchio A, Salmon ED. The spindle-assembly checkpoint in space and time. …

Identification of the sAPRIL binding peptide and its growth inhibition effects in the colorectal cancer cells.

BackgroundA proliferation-inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) super family. It binds to its specific receptors and is involved in multiple processes during tumorigenesis and tumor cells proliferation. High levels of APRIL expression are closely correlated to the growth, metastasis, and 5-FU drug resistance of colorectal cancer. The aim of this study was to identify a specific APRIL binding peptide (BP) able to block APRIL activity that could be used as a potential treatment for colorectal cancer.MethodsA phage display library was used to identify peptides tha

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… The antibodies used were against APRIL, cyclin D1, cyclin A, cyclin E, cyclin B1, CDK4, CDK6, p53, p27, and p16 (1:1000, Abcam, USA) and rabbit anti-GAPDH (1:2000, ZSGB-BIO, China). … The protein size of Cyclin D1 is 34 kDa, Cyclin A 49 kDa, Cyclin E 50 kDa, Cyclin B1 55 kDa, CDK4 34 kDa, CDK6 37 kDa, p53 53 kDa, p27 27 kDa, p16 40 kDa, and GAPDH 36 kDa. …

Acute Kidney Injury Associated with Anticancer Therapies: Small Molecules and Targeted Therapies.

Molecular targeted therapy has revolutionized cancer treatment by significantly improving patient survival compared with standard conventional chemotherapies. The use of these drugs targets specific molecules or targets, which block growth and spread of cancer cells. Many of these therapies have been approved for use with remarkable success in breast, blood, colorectal, lung, and ovarian cancers. The advantage over conventional chemotherapy is its ability to deliver drugs effectively with high specificity while being less toxic. Although known as "targeted," many of these agents lack specifici

Mechanisms of resistance to antibody-drug conjugates in cancer therapy: molecular basis and therapeutic strategies.

Antibody-drug conjugates (ADCs) have emerged as a transformative class in oncology, integrating the target specificity of monoclonal antibodies with the potent cytotoxicity of small-molecule payloads. By harnessing tumor-specific antigen recognition, ADCs enable the selective delivery of chemotherapeutic agents, thereby enhancing therapeutic efficacy while reducing systemic toxicity. Their clinical success across both hematologic malignancies and solid tumors underscores their potential to redefine targeted cancer therapy. However, the clinical durability of ADCs is increasingly undermined by

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… Cyclin B1, a key regulator of the G2/M transition of the cell cycle (G 2 -M) phase transition, accumulates in T-DM1-sensitive cells but not in resistant counterparts. … Suppression of cyclin B1 upregulation can partially restore T-DM1 sensitivity, suggesting that cyclin B1 expression levels may serve as a potential biomarker of T-DM1 efficacy [ 57 ] . In addition, dysregulation of apoptotic pathways can modulate cellular responsiveness to cytotoxic agents. …

Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review.

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells' sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene rever

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… U-2OS cells were arrested in G1 and S phases, and the expression levels of CDK1 , Cyclin-B1, and P27 genes decreased, the expression of Bcl-2 and Bcl-w anti-apoptotic genes decreased, and the expression of pro-apoptotic Bad and Caspase-3 genes was significantly upregulated. … By detecting the expression of intracellular proteins, the expression of Cyclin B1 and Cdc2, which regulate the cell cycle at the G2–M boundary, was downregulated. …

Platycodon grandiflorum, as a medicinal and food homologous plant: a comprehensive review of anti-tumor components, mechanisms, modern applications, and preventive healthcare.

Platycodon grandiflorum (Jacq.) A. D C. (P. grandiflorum), as a medicinal and edible plant, is widely distributed in China. In terms of Chinese medical theories, Traditional Chinese Medicine (TCM) believes that the root of P. grandiflorum has the functions of relieving sore throat, eliminating phlegm, and draining pus, and is widely used in lung diseases and respiratory system disorders. Modern pharmacological studies have shown that Platycodon grandiflorum saponin, flavonoids, polysaccharides, and phenolic acids are the main active components of P. grandiflorum, which have significant antitus

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… Cyclin B1 is a crucial constituent of the cyclin family, which can activate specific cyclin dependent kinases (CDKs) required for cell cycle progression ( 55 ). Activated Cyclin B1 can promote cells from the G2 phase to the M phase, and initiate mitotic progression ( 56 ). … In the study, Lee et al. ( 57 ) found that apigenin can trigger G2/M cell cycle arrest, inhibit the expression of Cyclin B1, Cdc2, and Cdc25c, thereby inhibiting the proliferation of HCT116 colon cancer cells. …

The Proliferative and Apoptotic Landscape of Basal-like Breast Cancer.

Basal-like breast cancer (BLBC) is an aggressive molecular subtype that represents up to 15% of breast cancers. It occurs in younger patients, and typically shows rapid development of locoregional and distant metastasis, resulting in a relatively high mortality rate. Its defining features are that it is positive for basal cytokeratins and, epidermal growth factor receptor and/or c-Kit. Problematically, it is typically negative for the estrogen receptor and human epidermal growth factor receptor 2 (HER2), which means that it is unsuitable for either hormone therapy or targeted HER2 therapy. As

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… The pan-CDK inhibitor, dinaciclib, inhibits the cell cycle, promoting activity of CDK9 to reduce cyclin B1 expression and cause G 2 /M arrest [ 98 ], and it is synthetically lethal in MYC-amplified BLBC, causing both proliferative arrest and apoptosis [ 99 ]. … Inhibition of cyclin dependent kinase 9 by dinaciclib suppresses cyclin B1 expression and tumor growth in triple negative breast cancer. Oncotarget. 2016;7:56864–56875. doi: 10.18632/oncotarget.10870. 99. …

RSK inhibitor BI-D1870 inhibits acute myeloid leukemia cell proliferation by targeting mitotic exit.

The 90 kDa Ribosomal S6 Kinase (RSK) drives cell proliferation and survival in cancers, although its oncogenic mechanism has not been well characterized. Phosphorylated level of RSK (T573) was increased in acute myeloid leukemia (AML) patients and associated with poor survival. To examine the role of RSK in AML, we analyzed apoptosis and the cell cycle profile following treatment with BI-D1870, a potent inhibitor of RSK. BI-D1870 treatment increased the G2/M population and induced apoptosis in AML cell lines and patient AML cells. Characterization of mitotic phases showed that the metaphase/an

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… The cellular level of Cyclin B1 increases at the time of cell exit from S, peaking at mitosis, and decreasing at the onset of anaphase (Supplementary Figure 3) [ 29 – 31 ]. Treatment with BI-D1870 significantly increased cell populations at G2 and M phases (%, control vs. … The following antibodies were used in western blot analyses: anti-Cyclin B1 (H433), anti- CDC2 [ 54 ], anti-β-Tubulin (H-235, Santa Cruz Biotechnology, Santa Cruz, CA, USA); ant-MAD2 [ 48 ], anti-phosphoserine/threonine (22A, BD Biosciences); anti-β-Actin (M2, Sigma); anti-cyclin A2 (BF683), anti-cleaved …

Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma.

Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation factor 2α (EIF2α) is a key player in canonical translation initiation and integrates diverse stress signals; when phosphorylated, it curbs global protein synthesis. This study evaluates EIF2α expression and phosphorylation in HNSCC. A small-molecule inhibitor of EIF2α dephosphorylation, salubrinal, was tested in vitro, followed by viability assays, flow cytome

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… G 2 /M arrest can be attributed to the depletion of cyclin B1 [ 61 ], which was not confirmed in this study. Instead, EIF2α phosphorylation downregulated the synthesis of cyclins D1 and A. Cyclin D1 is an unstable protein; its abundance directly depends on translation rate [ 62 ]. …

Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies.

Antibody-drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies' targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored

Non-Curcuminoids from Turmeric and Their Potential in Cancer Therapy and Anticancer Drug Delivery Formulations.

Over the past decades curcuminoids have been extensively studied for their biological activities such as antiulcer, antifibrotic, antiviral, antibacterial, antiprotozoal, antimutagenic, antifertility, antidiabetic, anticoagulant, antivenom, antioxidant, antihypotensive, antihypocholesteremic, and anticancer activities. With the perception of limited toxicity and cost, these compounds forms an integral part of cancer research and is well established as a potential anticancer agent. However, only few studies have focused on the other bioactive molecules of turmeric, known as non-curcuminoids, wh

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… Bin et al. explained that germacrone has proved to be beneficial as antitumor agent on human hepatoma cell lines (HepG2 and Bel 7402), by activating CDK1, inducing P21 and reducing the protein expression of cyclin B1. … This amplification was associated with cell apoptosis, G2/M phase cell cycle arrest and caused reduction in the cyclin B1 and its activating partner CDK1, which induced p21, along with the upregulation of p53 and ROS. …

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools.

Chronic kidney disease (CKD) is an increasing health burden (affecting approximately 13.4% of the population). Currently, no curative treatment options are available and treatment is focused on limiting the disease progression. The accumulation of senescent cells has been implicated in the development of kidney fibrosis by limiting tissue rejuvenation and through the secretion of pro-fibrotic and pro-inflammatory mediators termed as the senescence-associated secretory phenotype. The clearance of senescent cells in aging models results in improved kidney function, which shows promise for the op