Exploring paraptosis as a therapeutic approach in cancer treatment.

A variety of cell death pathways play critical roles in the onset and progression of multiple diseases. Paraptosis, a unique form of programmed cell death, has gained significant attention in recent years. Unlike apoptosis and necrosis, paraptosis is characterized by cytoplasmic vacuolization, swelling of the endoplasmic reticulum and mitochondria, and the absence of caspase activation.

CDK7/CDK9 mediates transcriptional activation to prime paraptosis in cancer cells.

Background: Paraptosis is a programmed cell death characterized by cytoplasmic vacuolation, which has been explored as an alternative method for cancer treatment and is associated with cancer resistance. However, the mechanisms underlying the progression of paraptosis in cancer cells remain largely unknown.

Methods: Paraptosis-inducing agents, CPYPP, cyclosporin A, and curcumin, were utilized to investigate the underlying mechanism of paraptosis.

[Corrigendum] Next‑generation sequencing analysis reveals that MTH‑3, a novel curcuminoid derivative, suppresses the invasion of MDA‑MB‑231 triple‑negative breast adenocarcinoma cells.

Subsequently to the publication of the article, an interested reader drew to the authors' attention that, in Fig. 2A on p. 5, the 'Control  (24 h)' and 'MTH‑3 (1 μM; 24 h)' data panels contained partially overlapping data, such that they appeared to have been derived from the same original source.

MRCK as a Potential Target for Claudin-Low Subtype of Breast Cancer.

To find new molecular targets for triple negative breast cancer (TNBC), we analyzed a large-scale drug screening dataset based on breast cancer subtypes. We discovered that BDP-9066, a specific MRCK inhibitor (MRCKi), may be an effective drug against TNBC. After confirming the efficacy and specificity of BDP-9066 against TNBC and , we further analyzed the underlying mechanism of specific activity of BDP-9066 against TNBC.

Inhibition of CDCP1 by 8-isopentenylnaringenin synergizes with EGFR inhibitors in lung cancer treatment.

CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance by regulating EGFR signaling pathways and is a potential target in lung cancer treatment. This study aims to identify a CDCP1 reducer that synergistically improves TKI treatment. Utilizing a high-throughput drug screening system, a phytoestrogen 8-isopentenylnaringenin (8PN) was identified.

Macrophage secretory IL-1β promotes docetaxel resistance in head and neck squamous carcinoma via SOD2/CAT-ICAM1 signaling.

Docetaxel (DTX) combined with cisplatin and 5-fluorouracil has been used as induction chemotherapy for head and neck squamous cell carcinoma (HNSCC). However, the development of acquired resistance remains a major obstacle to treatment response. Tumor-associated macrophages are associated with chemotherapeutic resistance.

Targeting 2-oxoglutarate dehydrogenase for cancer treatment.

Tricarboxylic acid (TCA) cycle, also called Krebs cycle or citric acid cycle, is an amphoteric pathway, contributing to catabolic degradation and anaplerotic reactions to supply precursors for macromolecule biosynthesis. Oxoglutarate dehydrogenase complex (OGDHc, also called α-ketoglutarate dehydrogenase) a highly regulated enzyme in TCA cycle, converts α-ketoglutarate (αKG) to succinyl-Coenzyme A in accompany with NADH generation for ATP generation through oxidative phosphorylation. The step collaborates with glutaminolysis at an intersectional point to govern αKG levels for energy production, nucleotide and amino acid syntheses, and the resources for macromolecule synthesis in cancer cells with rapid proliferation.

The Role of HO-1 and Its Crosstalk with Oxidative Stress in Cancer Cell Survival.

Heme oxygenases (HOs) act on heme degradation to produce carbon monoxide (CO), free iron, ferritin, and biliverdin. Upregulation of cellular HO-1 levels is signature of oxidative stress for its downstream effects particularly under pro-oxidative status. Subcellular traffics of HO-1 to different organelles constitute a network of interactions compromising a variety of effectors such as pro-oxidants, ROS, mitochondrial enzymes, and nucleic transcription factors.

Next‑generation sequencing analysis reveals that MTH‑3, a novel curcuminoid derivative, suppresses the invasion of MDA‑MB‑231 triple‑negative breast adenocarcinoma cells.

Triple‑negative breast cancer (TNBC) behaves aggressively in the invasive and metastatic states. Our research group recently developed a novel curcumin derivative, (1E,3Z,6E)-3-hydroxy-5-oxohepta-1,3,6-triene-1,7-diyl)bis(2‑methoxy-4,1‑phenylene)bis(3-hydroxy2-hydroxymethyl)-2‑methyl propanoate (MTH‑3), and previous studies showed that MTH‑3 inhibits TNBC proliferation and induces apoptosis and with a superior bioavailability and absorption than curcumin. In the present study, the effects of MTH‑3 on TNBC cell invasion were examined using various assays and gelatin zymography, and western blot analysis.

Aptamer-guided targeting of the intracellular long-noncoding RNA .

Long non-coding RNAs (lncRNAs) are increasingly recognized as promising targets in cancer treatment. However, compared to targeting the ordinary protein-coding genes, suppressing non-coding RNAs expressed in cancer cells has been a more challenging task. The major hurdles lay on the requirement of a tumor-specific delivery system for the designated inhibitor to suppress the target transcripts within the cellular compartment.

Unrestricted Feed Intake Induces β-Cell Death and Impairs Insulin Secretion in Broiler Breeder Hens.

Past studies regarding to insulin secretion and glucose disposal in chickens were focused on rapidly growing juvenile broilers and may not reflect glucose/insulin physiology in adulthood. The study aimed to assess insulin secretion and glucose disposal in respect to restricted (R) vs. ad libitum (Ad) feed intake for obesity development in broiler breeder hens.

Cytotoxicity Produced by Silicate Nanoplatelets: Study of Cell Death Mechanisms.

Nano-silicate platelets (NSP), an exfoliated product from natural clays, have been validated for biosafety and as an effective supplement to alleviate mycotoxicosis. Since NSP induced noticeable cell death, we therefore investigated further the mechanism of cytotoxicity caused by NSP. Exposure to NSP impaired membrane integrity and caused cell death in a dose-dependent manner.

EFHD2 contributes to non-small cell lung cancer cisplatin resistance by the activation of NOX4-ROS-ABCC1 axis.

Recurrence and metastasis remain the major cause of cancer mortality. Even for early-stage lung cancer, adjuvant chemotherapy yields merely slight increase to patient survival. EF-hand domain-containing protein D2 (EFHD2) has recently been implicated in recurrence of patients with stage I lung adenocarcinoma.

DOCK1 Regulates Growth and Motility through the RRP1B-Claudin-1 Pathway in Claudin-Low Breast Cancer Cells.

Dedicator of cytokinesis 1 (DOCK1) is a critical regulator of cancer metastasis. Claudins are transmembrane proteins that play a role in epithelial barrier integrity. Due to a loss or low expression of claudins (CLDN), the claudin-low type of triple-negative breast cancer (TNBC) is characterized by a mesenchymal-like phenotype with strong metastatic potential.

Design, synthesis and evaluation of antiproliferative activity of fluorinated betulinic acid.

Betulinic acid (BA), a pentacyclic triterpenoid, exhibits broad spectrum antiproliferative activity, but generally with only modest potency. To improve BA's pharmacological properties, fluorine was introduced as a single atom at C-2, creating two diastereomers, or in a trifluoromethyl group at C-3. We evaluated the impact of these groups on antiproliferative activity against five human tumor cell lines.

Long noncoding RNA HOTAIR promotes invasion of breast cancer cells through chondroitin sulfotransferase CHST15.

The long noncoding RNA HOTAIR plays significant roles in promoting cancer metastasis. However, how it conveys an invasive advantage in cancer cells is not clear. Here we identify the chondroitin sulfotransferase CHST15 (GalNAc4S-6ST) as a novel HOX transcript antisense intergenic RNA (HOTAIR) target gene using RNA profiling and show that CHST15 is required for HOTAIR-mediated invasiveness in breast cancer cells.

A Dual Role of Heme Oxygenase-1 in Cancer Cells.

Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, and it has been suggested to demonstrate cytoprotective effects against various stress-related conditions. HO-1 is commonly regarded as a survival molecule, exerting an important role in cancer progression and its inhibition is considered beneficial in a number of cancers. However, increasing studies have shown a dark side of HO-1, in which HO-1 acts as a critical mediator in ferroptosis induction and plays a causative factor for the progression of several diseases.

Heme oxygenase-1 mediates BAY 11-7085 induced ferroptosis.

Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment. BAY 11-7085 (BAY), which is a well-known IκBα inhibitor, suppressed viability in cancer cells via induction of ferroptotic death in an NF-κB-independent manner. Reactive oxygen species scavenging, relief of lipid peroxidation, replenishment of glutathione and thiol-containing agents, as well as iron chelation, rescued BAY-induced cell death.

Effect of bis(hydroxymethyl) alkanoate curcuminoid derivative MTH-3 on cell cycle arrest, apoptotic and autophagic pathway in triple-negative breast adenocarcinoma MDA-MB-231 cells: An in vitro study.

Curcumin has been shown to exert potential antitumor activity in vitro and in vivo involved in multiple signaling pathways. However, the application of curcumin is still limited because of its poor hydrophilicity and low bio-availability. In the present study, we investigated the therapeutic effects of a novel and water soluble bis(hydroxymethyl) alkanoate curcuminoid derivative, MTH-3, on human breast adenocarcinoma MDA-MB-231 cells.

New bis(hydroxymethyl) alkanoate curcuminoid derivatives exhibit activity against triple-negative breast cancer in vitro and in vivo.

Novel bis(hydroxymethyl) alkanoate curcuminoid derivatives were designed, synthesized and screened for in vitro antiproliferative and in vivo antitumor activity. Selected new compound 9a and curcumin were further evaluated for inhibitory activity against ER/PR breast cancer (MCF-7, T47D), HER 2 breast cancer (SKBR3, BT474, and MDA-MB-457) and triple negative breast cancer (TNBC) (HS-578T, MDA-MB-157, and MDA-MB-468) cell lines. In addition, compound 9a was evaluated in the MDA-MB-231 xenograft nude mice model.

A novel microtubule inhibitor, MT3-037, causes cancer cell apoptosis by inducing mitotic arrest and interfering with microtubule dynamics.

We investigated the anticancer potential of a new synthetic compound, 7-(3-fluorophenyl)-4-methylpyrido-[2,3-d]pyrimidin-5(8H)-one (MT3-037). We found that MT3-037 effectively decreased the cancer cell viability by inducing apoptosis. MT3-037 treatments led to cell cycle arrest at M phase, with a marked increase in both expression of cyclin B1 and cyclin-dependent kinase 1 (CDK1) as well as in CDK1 kinase activity.

Dietary components as epigenetic-regulating agents against cancer.

Carcinogenesis is a complicated process that involves the deregulation of epigenetics resulting in cellular transformational events, such proliferation, differentiation, and metastasis. Epigenetic machinery changes the accessibility of chromatin to transcriptional regulation through DNA modification. The collaboration of epigenetics and gene transcriptional regulation creates a suitable microenvironment for cancer development, which is proved by the alternation in cell proliferation, differentiation, division, metabolism, DNA repair and movement.

The newly synthesized 2-arylnaphthyridin-4-one, CSC-3436, induces apoptosis of non-small cell lung cancer cells by inhibiting tubulin dynamics and activating CDK1.

Purpose: To investigate the anticancer therapeutic potential of a new synthetic compound, 2-(3-hydroxyphenyl)-5-methylnaphthyridin-4-one (CSC-3436), on non-small cell lung cancer (NSCLC) cells.

Methods: Cell viability was determined by MTT assay. Cell cycle distribution was assessed by propidium iodide staining and subjected to flow cytometry analysis.

Restored glial glutamate transporter EAAT2 function as a potential therapeutic approach for Alzheimer's disease.

Glutamatergic systems play a critical role in cognitive functions and are known to be defective in Alzheimer's disease (AD) patients. Previous literature has indicated that glial glutamate transporter EAAT2 plays an essential role in cognitive functions and that loss of EAAT2 protein is a common phenomenon observed in AD patients and animal models. In the current study, we investigated whether restored EAAT2 protein and function could benefit cognitive functions and pathology in APPSw,Ind mice, an animal model of AD.