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Revolutionizing ovarian cancer therapy by drug repositioning for accelerated and cost-effective treatments.

Drug repositioning, the practice of identifying novel applications for existing drugs beyond their originally intended medical indications, stands as a transformative strategy revolutionizing pharmaceutical productivity. In contrast to conventional drug development approaches, this innovative method has proven to be exceptionally effective. This is particularly relevant for cancer therapy, where the demand for groundbreaking treatments continues to grow. This review focuses on drug repositioning for ovarian cancer treatment, showcasing a comprehensive exploration grounded in thorough in vitro

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… Besides, ATO induces cellular stress, autophagy, apoptosis, and arrest cell cycle at G1 phase through Akt/mTOR pathway inhibition and MAPK pathway activation ( 102 , 103 ). … Ivermectin arrests cell cycle at G0-G1 phase by increasing the synthesis of p21, reducing proliferating cell nuclear antigen (PCNA), cyclin E, and cyclin D protein levels in breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-468) ( 163 ). …

Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives.

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of "onco-channelopathy". Here, we review the contribution of ion channels and transporters in multiple myeloma (

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… Deregulation of K + current inhibits MM cells’ proliferation by blocking cell cycle progression at the G1 phase and by modulating intracellular pathways’ activation via the regulation of cell volume [ 23 ]. … Furthermore, the pharmacological treatment with arsenic trioxide (ATO), which decreases Ik v currents and depolarizes cells in a concentration-dependent manner, inhibits MM cell proliferation by arresting RPMI8226 cells at the G0/G1 phase [ 24 ]. …

Prospective Study of Multiparametric Renal MRI for CKD Progression (AFiRM).

IntroductionChronic kidney disease (CKD) has major population health implications, but current imaging approaches provide limited pathophysiological insights. We designed a study to evaluate renal multiparametric magnetic resonance imaging (MRI; mpMRI) as a tool to improve diagnosis, risk stratification, disease monitoring, and therapeutic decision-making in CKD.MethodsThe application of functional renal MRI to improve assessment of CKD (AFiRM study; NCT04238299) is a multicenter, prospective, observational cohort study in people with CKD. Participants underwent renal mpMRI using the harmonize

Toxicity management strategies for next-generation novel therapeutics in multiple myeloma.

The therapeutic options available for patients with multiple myeloma have greatly expanded over the past decade and incorporating these novel agents into routine clinical practice has significantly improved outcomes. The next generation of therapeutics is available for relapsed and refractory patients either as standard of care or in clinical trial, and these drugs represent a generational paradigm shift. Patients now have access to a multitude of novel immunotherapeutics, including monoclonal antibodies, an antibody-drug conjugate, chimeric antigen receptor T-cells (CAR-T), and bispecific T-c

The multiple biological activities of hyperoside: from molecular mechanisms to therapeutic perspectives in neoplastic and non-neoplastic diseases.

In recent years, hyperoside (quercetin 3-O-β-D-galactopyranoside) has garnered significant attention due to its diverse biological effects, which include vasoprotective, antioxidant, anti-inflammatory, and anti-tumor properties. Notably, hyperoside has shown remarkable potential in cancer therapy by targeting multiple mechanisms; it induces apoptosis, inhibits proliferation, blocks angiogenesis, and reduces the metastatic potential of cancer cells. Furthermore, hyperoside enhances the sensitivity of cancer cells to chemotherapy by modulating key signaling pathways. Beyond neoplastic diseases,

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… Hyperoside significantly inhibited the proliferation of osteosarcoma cells (U2OS and MG63) by inducing cell cycle arrest in the G0/G1 phase. … This inhibitory effect is closely associated with the increased expression levels of cell cycle regulatory factors p21 and p27, which prevent cells from transitioning from the G1 phase to the S phase. …

Drug Repurposing for Cancer Treatment: A Comprehensive Review.

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therap

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… Clofoctol promotes endoplasmic reticulum (ER) stress via activating the unfolded protein response (UPR) pathway, resulting in G1 phase cell cycle arrest in cancer cells. … Repurposed Medications in the Treatment of Hepatocellular Carcinoma (HCC) Pimozide, an antipsychotic medication, can potentially suppress the growth of hepatocellular carcinoma (HCC) cell lines in laboratory settings by triggering apoptosis during the G0/G1 phase. …

Recent advances in precision oncology research.

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Selenium Compounds as Novel Potential Anticancer Agents.

The high number of new cancer incidences and the associated mortality continue to be alarming, leading to the search for new therapies that would be more effective and less burdensome for patients. As there is evidence that Se compounds can have chemopreventive activity, studies have begun to establish whether these compounds can also affect already existing cancers. This review aims to discuss the different classes of Se-containing compounds, both organic and inorganic, natural and synthetic, and the mechanisms and molecular targets of their anticancer activity. The chemical classes discussed

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review.

Sinomenine, an isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, has been extensively studied for its derivatives as bioactive agents. This review concentrates on the research advancements in the biological activities and action mechanisms of sinomenine-related compounds until November 2023. The findings indicate a broad spectrum of pharmacological effects, including antitumor, anti-inflammation, neuroprotection, and immunosuppressive properties. These compounds are notably effective against breast, lung, liver, and prostate cancers, exhibiting IC50 values of appro

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… Lu et al. synthesized sinomenine hydrochloride (SH) and discovered that SH (0.5–2 µM) inhibited the growth of Hep3B and SMMC7721 cells, leading to G1 phase arrest through the augmentation of p21. … The mechanism involved blocking cell cycle progression from the G1 phase to the S phase and enhancing caspase-3 cleavage [ 172 ]. Additionally, in 2007, Y.Y. …

Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma.

The proteasome is crucial for the degradation of intracellular proteins and plays an important role in mediating a number of cell survival and progression events by controlling the levels of key regulatory proteins such as cyclins and caspases in both normal and tumor cells. However, compared to normal cells, cancer cells are more dependent on the ubiquitin proteasome pathway (UPP) due to the accumulation of proteins in response to uncontrolled gene transcription, allowing proteasome to become a potent therapeutic target for human cancers such as multiple myeloma (MM). Up to date, three protea

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… Expression of Cyclin D1 is regulated under the NFκB pathway and plays a major role in cancer progression by acting as the key regulator of the late G1 phase of the cell cycle. … Stabilization of p27 by proteasome inhibition is important as it suppresses the activity of CDK2/Cyclin E and CDK2/Cyclin A complexes mediating progression to the G1 phase and suppressing transition to the S phase ( 27 , 56 ). …

Targeting the ubiquitin-proteasome system: a novel therapeutic strategy for neuroblastoma.

Neuroblastoma (NB) stands as a common and formidable malignant tumor among children, characterized by marked tumor heterogeneity and resistance to conventional treatments. Central to the regulation of protein stability, localization, and function is the process of ubiquitination-a critical protein modification. The therapeutic potential of drugs that target deubiquitination, demonstrated in the treatment of refractory multiple myeloma, warrants investigation in the context of NB. This review endeavors to demystify the intricate biological implications of ubiquitination within NB pathology, syn

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… NVP-BEZ235 is a dual kinase inhibitor targeting both PI3K and mTOR kinases and has been shown to inhibit NB cell proliferation and induce cell cycle arrest at the G0/G1 phase ( 58 , 59 ). …

Next-Generation HDAC Inhibitors: Advancing Zinc-Binding Group Design for Enhanced Cancer Therapy.

Histone deacetylases (HDACs) are pivotal epigenetic regulators that control gene expression, cell proliferation, and differentiation, and their dysregulation is closely associated with the onset and progression of multiple cancers. The therapeutic importance of these enzymes is reflected by FDA approval of HDAC inhibitors for oncology indications. Despite this clinical success, most FDA-approved agents employ conventional zinc-binding groups (ZBGs) such as hydroxamic acid and 2-aminoanilide, which are frequently linked to metabolic instability, genotoxicity, and poor pharmacokinetic behavior.

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… Mechanistic studies revealed that St.5 induces G1 phase arrest through Cyclin D1 downregulation and triggers intrinsic apoptosis via caspase-3 activation and an elevated Bax/Bcl-2 ratio. … Several derivatives displayed remarkable enzyme inhibition, with DLC-1 showing exceptional PARP-1 potency and strong antiproliferative effects across breast cancer cell lines, inducing G1 phase arrest and apoptosis. …

Estimation of Future Patient Populations Eligible for Radioligand Therapies in the EU and the UK: A Modelling Study.

BackgroundThe eligible patient population for radioligand therapies (RLTs) has the potential to grow rapidly in the coming years. European healthcare systems may be ill-prepared to provide the additional treatment capacity required on top of current workload. To address this challenge, data on the size of the eligible patient pool and the potential utilisation of RLTs are needed.MethodsThe maximum pool of patients theoretically eligible for RLTs over the next decade was estimated for the 27 EU member states (EU-27) using incidence data, and additionally for France, Germany, Italy, Spain (EU-4)

Integrating Nature Into Oncology: Enhancing Hematological Malignancies Therapies With Natural Medicine.

Hematological malignancies are complex clonal disorders that pose a significant threat to human health. Current treatment modalities, including radiotherapy, chemotherapy, immunotherapy, and bone marrow transplantation, have demonstrated efficacy but are often limited by side effects, drug resistance, and suboptimal cure rates. Natural medicines, as key elements of complementary and alternative medicine, exhibit considerable potential in combating hematological cancers. Particularly when used in combination with conventional therapies, they can enhance treatment efficacy and reverse drug resis

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… Additionally, matrine induces dose‐dependent G0/G1 phase arrest, effectively inhibiting the malignant progression of SU‐DHL‐16 and OCI‐LY3 cells [ 48 ]. … Ishikawa et al. investigated the effects of ART on PEL cell lines and found that ART downregulates the expression of Cyclin D1/D2, CDK2/6, and c‐Myc via the NF‐κB/AP‐1 signaling pathway, inducing G1 phase cell cycle arrest. …

A Review of The Synergistic Effects of Curcumin with Proteasome Inhibitors in Multiple Myeloma Preclinical Models.

Proteasome inhibitors are the cornerstone of multiple myeloma treatment, but challenges still remain despite the increased survival rates. We conducted a review on the role of curcumin, a natural product, as an adjunct to bortezomib and carfilzomib in preclinical multiple myeloma models. Four studies reviewed showed enhanced anticancer effects when curcumin was combined with bortezomib compared to either treatment alone. Two additional studies showed similar results with carfilzomib. Synergistic mechanisms include inhibition of NF-kB, IL-6-induced signaling pathways, JNK pathway modulation, an

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… (MM.1S, MM.1R cell lines) | Curcumin and carfilzomib | - Enhanced cytotoxicity, apoptosis Allegra et al 23 , Toxicol In Vitro. 2018 | In vitro (multiple myeloma U266 cells) | Curcumin and carfilzomib | - Enhanced apoptosis, NF-kB downregulation, p53/p21 upregulation, increased cell cycle arrest G0/G1 … A combination of curcumin and carfilzomib showed downregulation of NF-kB activity, upregulation of p53 and p21, and increased cell cycle arrest in G0/G1 phase ( Figure 2 ). 23 Figure 2. Synergistic effects of curcumin and proteasome inhibitors on pathways involved in MM cells. …

Covalent targeting of PSMD14 by Eupalinolide B induces oncoprotein degradation and apoptosis in acute promyelocytic leukemia cells.

Treatment of acute promyelocytic leukemia (APL) remains challenged by toxicities associated with current regimens, highlighting the need for novel and safer therapeutic agents. Here, we identify Eupalinolide B (EB), a natural sesquiterpene lactone isolated from Eupatorium lindleyanum DC., as a potent anti-leukemic compound targeting the human APL-derived HL-60 cell line. Through integrated chemoproteomic profiling and functional validation, we demonstrate that EB covalently binds and inhibits 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a deubiquitinase enzyme (DUB) within the 19S

Panobinostat reduces hypoxia-induced cisplatin resistance of non-small cell lung carcinoma cells via HIF-1α destabilization.

BackgroundLung cancer is one of the most frequent cancer types and the leading cause of cancer death worldwide. Cisplatin is a widely used chemotherapeutic for non-small cell lung carcinoma (NSCLC), however, its positive effects are diminished under hypoxia. We wanted to determine if co-treatment with cisplatin and histone deacetalyse (HDAC) inhibitor panobinostat can reduce hypoxia-induced cisplatin resistance in NSCLC cells, and to elucidate mechanism involved.MethodsExpression status of different HDACS was determined in two cell lines and in tumor tissue from 20 patients. Cells were treated

Current Uses of Mushrooms in Cancer Treatment and Their Anticancer Mechanisms.

Cancer is the leading cause of mortality worldwide. Various chemotherapeutic drugs have been extensively used for cancer treatment. However, current anticancer drugs cause severe side effects and induce resistance. Therefore, the development of novel and effective anticancer agents with minimal or no side effects is important. Notably, natural compounds have been highlighted as anticancer drugs. Among them, many researchers have focused on mushrooms that have biological activities, including antitumor activity. The aim of this review is to discuss the anticancer potential of different mushroom

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… Antrodia camphorata grown on germinated brown rice suppressed human colon cancer cell proliferation by upregulating G0/G1 phase arrest and apoptosis and reducing β-catenin signaling [ 40 ]. … Antrodia camphorata grown on germinated brown rice inhibits HT-29 human colon carcinoma proliferation through inducing G0/G1 phase arrest and apoptosis by targeting the β-catenin signaling. J. Med. Food. 2013;16:681–691. doi: 10.1089/jmf.2012.2605. 30. Park D.K., Park H.-J. …

Механистические и переводческие данные о натуральных продуктах растительного происхождения в предклинических исследованиях по миеломе: текущие данные.

Множественная миелома (ММ) — гематологическая порча, характеризующаяся клональным распространением аномальных плазменных клеток с ярко выраженной гетерогенностью и терапевтической рефлексорностью. Несмотря на внедрение протеазонных ингибиторов (ИП), иммуноводных препаратов (ИМИД), моноклонных антител (mAbs) и химерика антигенного рецептора Т-клеток (CAR-T), рецидивы и резистентность к лекарствам по-прежнему остаются серьезными проблемами, требующими неотложного решения. В последние годы природные продукты растительного происхождения привлекают все большее внимание в связи с их многоцелевым син

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… phase arrest and apoptosis by synergistically activating the p53/p21 axis [ 39 ]. … Mechanisms include inhibition of NF-κB and STAT3 signaling pathways, downregulation of pro-proliferative proteins (e.g., cyclin D1) and anti-apoptotic proteins (e.g., Bcl-2, Mcl-1, survivin), activation of JNK, and suppression of Akt phosphorylation, thereby inducing cell cycle arrest (G0/G1 phase) and …

Natural biomolecules and derivatives as anticancer immunomodulatory agents.

Despite advancements in chemotherapy, the issue of resistance and non-responsiveness to many chemotherapeutic drugs that are currently in clinical use still remains. Recently, cancer immunotherapy has gathered attention as a novel treatment against select cancers. Immunomodulation is also emerging as an effective strategy to improve efficacy. Natural phytochemicals, with known anticancer properties, been reported to mediate their effects by modulating both traditional cancer pathways and immunity. The mechanism of phytochemical mediated-immunomodulatory activity may be attributed to the remode