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The role of proteasomes in tumorigenesis.

Protein homeostasis is the basis of normal life activities, and the proteasome family plays an extremely important function in this process. The proteasome 20S is a concentric circle structure with two α rings and two β rings overlapped. The proteasome 20S can perform both ATP-dependent and non-ATP-dependent ubiquitination proteasome degradation by binding to various subunits (such as 19S, 11S, and 200 PA), which is performed by its active subunit β1, β2, and β5. The proteasome can degrade misfolded, excess proteins to maintain homeostasis. At the same time, it can be utilized by tumors to deg

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… As a result, inhibiting action by the proteasome leads to up-regulation of these proteins, which may lead to apoptosis in tumoral cells in vitro . 110 , 111 , 112 Given that the cyclin-D1-CDK4 complex is required for the G1-S phase and cyclin B1-CDK1 complex is required for mitosis, 113 , 114 , 115 proteasome …

New targets for the treatment of follicular lymphoma.

The last two decades have witnessed striking advances in our understanding of the biological factors underlying the development of Follicular lymphoma (FL). Development of newer treatment approaches have improved the outlook for many individuals with these disorders; however, with these advances come new questions. Given the long-term survival of patients with FL, drugs with favourable side-effect profile and minimal long-term risks are desired. FL is incurable with current treatment modalities. It often runs an indolent course with multiple relapses and progressively shorter intervals of remi

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… TQ was also found to arrest G2/M phase of cell cycle which was associated with an increase in p53 expression and down-regulation of cyclin B1 protein in spindle carcinoma cells. … TQ induced apoptosis was mediated via p53 which can regulate G2/M transition through either induction of p21 or 14-3-3sigma, a protein that normally sequesters cyclin B1-CDC2 complexes in the cytoplasm [ 112 - 115 ]. …

Tumour Cell Size Control and Its Impact on Tumour Cell Function.

Cell size is an important component of cell morphological characteristics. It reflects the characteristics of the cell type, nutritional status, growth stage and physiological function. The cell size of cells of the same type tends to be homogeneous and stable. However, in tumour cells, mutations in cell cycle genes and cytoskeletal genes and overexpression of the corresponding signalling pathways often lead to large variations in tumour cell size. Tumour cells regulate cell size and growth and proliferation through multiple signalling pathways, such as PI3K/Akt/mTOR, Myc and Hippo pathways, w

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… Lu , et al., “ Hyperactivation of p53 Contributes to Mitotic Catastrophe in Podocytes Through Regulation of the Wee1/CDK1/Cyclin B1 Axis ,” Renal Failure 46 , no. 2 ( 2024 ): 2365408 . 38874119 10.1080/0886022X.2024.2365408 PMC11182053 59 D. Hiraoka , E. Hosoda , K. Chiba , and T. …

Using Prognosis-Related Gene Expression Signature and Connectivity Map for Personalized Drug Repositioning in Multiple Myeloma.

BACKGROUND Multiple myeloma (MM) is the second most common hematologic cancer with poor prognosis. Novel therapeutic strategies are needed to decrease the high mortality rate. The aim of this study was to identify prospective agents for MM. MATERIAL AND METHODS A microarray dataset was mined, which contains the transcriptome profiles of 588 MM patients. Univariate Cox analysis was performed to analyze the relationships between genes and clinical outcome. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were determined. Protective and risky genes were uploaded to Connec

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… This SQ29548 facilitated cell G2/M phase delay in MM cells in addition to decreasing cyclin B1/CDK1 mRNA and protein expression [ 17 ]. Moreover, P276-00 and dinaciclib (SCH727965) are also small molecule inhibitors of CDK1 [ 18 , 19 ]. …

Patient-Derived Organoids Can Guide Personalized-Therapies for Patients with Advanced Breast Cancer.

Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstr

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… Western blotting analysis demonstrated that gemcitabine more efficiently reduced activated transcription factor (p‐STAT3), increased mitotic checkpoint protein (cyclin B1 and cyclin A), and increased pro‐apoptotic protein (cleaved caspase‐3) expression in the sensitive organoid lines (Figure 3E ). … With paclitaxel treatment, downregulation of cyclin A and upregulation of cyclin B1, p‐BCL, and cleaved caspase‐3 was observed in the sensitive organoid lines (Figure 3F ). …

Marine-Derived Compounds: A New Horizon in Cancer, Renal, and Metabolic Disease Therapeutics.

Marine-derived compounds represent a rich source of structurally diverse molecules with therapeutic potential for cancer, renal disorders, metabolic-associated fatty liver disease (MAFLD), and atherosclerosis. This review systematically evaluates recent advances, highlighting compounds such as Microcolin H, Benzosceptrin C, S14, HN-001, Equisetin, glycosides (e.g., cucumarioside A2-2), ilimaquinone, and Aplidin (plitidepsin). Key mechanisms include autophagy modulation, immune checkpoint inhibition, anti-inflammatory effects, and mitochondrial homeostasis. Novel findings reveal glycosides' dua

Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase.

Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy. We determ

Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications.

Post-translational modifications (PTMs) play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality. PTMs involve the covalent attachment of distinct chemical groups, such as succinyl, crotonyl, and lactyl, at specific protein sites, which alter protein structure, function, stability, and activity, ultimately influencing biological processes. Recently, metabolically derived short-chain acylation modifications (with acyl groups containing fewer than six carbon atoms) have been progressively identified, such as butyrylation, succinylation, crotonylation

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… autotaxin Bcl‐2 associated X β‐hydroxybutyrate dehydrogenase 1 beclin 1 polycomb complex protein BMI‐1 bromodomain PHD finger transcription factor bromodomain‐containing protein 9 brahma‐related gene 1 protein BUB1 mitotic checkpoint serine/threonine kinase B cap structure CREB‐binding protein cyclin … Similarly, in lung cancer, the aldoketoreductase family 1 B10 (AKR1B10) heightens histone H4K12 lactylation through the Warburg effect, stimulates the transcription of cyclin B1 ( CCNB1 ), accelerates DNA replication and the cell cycle, and fosters acquired resistance to pemetrexed in lung cancer brain …

Изучение точных методов лечения иммунизированных подстрекательских заболеваний: использование бесконечного потенциала доставки нуклеиновой кислоты.

Неизлечимые подстрекательские заболевания (ИМИД) создают неизмеримое бремя для отдельных лиц и общества. В то время как традиционное использование иммунодепрессантов и лекарственных средств для борьбы с заболеваниями обеспечивает частичную помощь и контроль, их неизбежные побочные эффекты и ограниченная эффективность ставят под сомнение возможность найти лекарство. Перспективные лекарства от нуклеиновой кислоты продемонстрировали способность оказывать точное воздействие на молекулярном уровне, при этом различные классы нуклеиновых кислот выполняют регулирующие функции с помощью различных механ

A Perspective on Withania somnifera Modulating Antitumor Immunity in Targeting Prostate Cancer.

Medicinal plants serve as a lead source of bioactive compounds and have been an integral part of day-to-day life in treating various disease conditions since ancient times. Withaferin A (WFA), a bioactive ingredient of Withania somnifera, has been used for health and medicinal purposes for its adaptogenic, anti-inflammatory, and anticancer properties long before the published literature came into existence. Nearly 25% of pharmaceutical drugs are derived from medicinal plants, classified as dietary supplements. The bioactive compounds in these supplements may serve as chemotherapeutic substance

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… WFA prevents Cdk1/cyclin B1 complex formation, a critical step of cell cycle progression in gastric cancer, by dephosphorylating Cdk1 at Thr161 and p21 upregulation in glioblastome [ 16 ]. …

Combinational Antitumor Strategies Based on the Active Ingredients of Toad Skin and Toad Venom.

A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic

The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.

Ubiquitination, a highly adaptable post-translational modification, plays a pivotal role in maintaining cellular protein homeostasis, encompassing cancer chemoresistance-associated proteins. Recent findings have indicated a potential correlation between perturbations in the ubiquitination process and the emergence of drug resistance in CRC cancer. Consequently, numerous studies have spurred the advancement of compounds specifically designed to target ubiquitinates, offering promising prospects for cancer therapy. In this review, we highlight the role of ubiquitination enzymes associated with c

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… Among these, activation of APC/C CDC20 subsequently mediates proteasomal degradation of cyclin B1 and securin, promoting chromosome segregation and late-phase onset (Singleton and Uhlmann 2017 ; Zhou et al. 2019 ). … In addition, APC/C CDH1 mediates the ubiquitination and proteasomal degradation of a large number of mitotic and G1 regulators, including cyclin B1, PLK1, CDC20, FOXM1, and SKP2, facilitating irreversible mitotic exit and G1 maintenance (Li and Zhang 2009 ). …

Iron deprivation in cancer--potential therapeutic implications.

Iron is essential for normal cellular function. It participates in a wide variety of cellular processes, including cellular respiration, DNA synthesis, and macromolecule biosynthesis. Iron is required for cell growth and proliferation, and changes in intracellular iron availability can have significant effects on cell cycle regulation, cellular metabolism, and cell division. Perhaps not surprisingly then, neoplastic cells have been found to have higher iron requirements than normal, non-malignant cells. Iron depletion through chelation has been explored as a possible therapeutic intervention i

The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities.

Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone modifications and their therapeutic targeting in endometriosis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The current manuscript represents the most comprehensive, up-to-date review of the literature focusing on the parti

Withania somnifera: Progress towards a Pharmaceutical Agent for Immunomodulation and Cancer Therapeutics.

Chemotherapy is one of the prime treatment options for cancer. However, the key issues with traditional chemotherapy are recurrence of cancer, development of resistance to chemotherapeutic agents, affordability, late-stage detection, serious health consequences, and inaccessibility. Hence, there is an urgent need to find innovative and cost-effective therapies that can target multiple gene products with minimal adverse reactions. Natural phytochemicals originating from plants constitute a significant proportion of the possible therapeutic agents. In this article, we reviewed the advances and t

Bortezomib in mantle cell lymphoma: comparative therapeutic outcomes.

Mantle cell lymphoma (MCL) is an incurable, typically aggressive subtype of non-Hodgkin lymphoma, accounting for 4%-7% of newly diagnosed non-Hodgkin lymphoma cases. Chemoresistance commonly ensues in MCL, and patients with this heterogeneous disease invariably relapse, underscoring the unmet need for better therapies. Over the past few years, several novel agents with promising activity and unique mechanisms of action have been deemed effective in MCL. Bortezomib is a reversible proteasome inhibitor, approved as a single agent for patients with relapsed/refractory MCL who have received at lea

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill.

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-

Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.

Peripheral nerves provide a direct connection between the brain and the tumor microenvironment. This connection allows the nervous system to influence processes associated with the development, progression, and metastasis of different tumor types. Therefore, tumor innervation by peripheral nerve fibers is currently emerging as a characteristic that contributes to multiple hallmarks of cancer. Several experimental studies have shown that cancer progression involves actively inducing the ingrowth of autonomic and sensory nerve fibers into tumor tissue. In this process, known as neoaxonogenesis,

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties

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… HDACIs, particularly butyrate, also inhibit directly colon carcinogenesis, by decreasing the expression of cyclin B1 gene (a cell cycle promoter) in colon cancers cells, as shown in vitro [ 45 ]. … The histone deacetylase inhibitor butyrate downregulates cyclin B1 gene expression via a p21/WAF-1-dependent mechanism in human colon cancer cells. Am. J. Physiol.—Gastrointest. Liver Physiol. 2005;289:G696–G703. doi: 10.1152/ajpgi.00575.2004. 46. …

Deciphering the impact of circRNA-mediated autophagy on tumor therapeutic resistance: a novel perspective.

Cancer therapeutic resistance remains a significant challenge in the pursuit of effective treatment strategies. Circular RNAs (circRNAs), a class of non-coding RNAs, have recently emerged as key regulators of various biological processes, including cancer progression and drug resistance. This review highlights the emerging role of circRNAs-mediated autophagy in cancer therapeutic resistance, a cellular process that plays a dual role in cancer by promoting both cell survival and death. Increasing evidence suggests that circRNAs can modulate autophagy pathways, thereby influencing the response o

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… B1↑ | Promotion | GEM resistance | [ 150 ] TC | circEIF6↑ | hsa_circ_0060060 | EIF6 | miR-144-3p | TGF-α↑ | Promotion | DDP resistance | [ 154 ] BC | circABCB10↑ | hsa_circ_0008717 | ABCB10 | let-7a-5p | DUSP7↑ | Promotion | PTX resistance | [ 155 ] circ_0006528↑ | hsa_circ_0006528 | PRELID2 | miR-1299 … In RC cells treated with GEM, hsa_circ_0035483 induces the expression of cyclin B1 by suppressing miR-335. This, in turn, increases the levels of LC3B and inhibits caspase3 expression, thereby activating autophagy and promoting resistance to GEM [ 150 ]. …