Anethole mitigates H2 O2 -induced inflammation in HIG-82 synoviocytes by suppressing the aquaporin 1 expression and activating the protein kinase A pathway.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting approximately 1% of the global population, with a higher prevalence in women than in men. Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of RA. Anethole, a prominent compound derived from fennel (Foeniculum vulgare), possesses a spectrum of therapeutic properties, including anti-arthritic, anti-inflammatory, antioxidant, and tumor-suppressive effects. However, its specific impact on RA remains underexplored. This study sought to uncover the potential therapeutic value of anethole in treating RA by employing an H2 O2 -induced inflammation model with HIG-82 synovial cells. Our results demonstrated that exposure to H2 O2 induced the inflammation and apoptosis in these cells. Remarkably, anethole treatment effectively countered these inflammatory and apoptotic processes triggered by H2 O2 . Moreover, we identified the aquaporin 1 (AQP1) and protein kinase A (PKA) pathway as critical regulators of inflammation and apoptosis. H2 O2 stimulation led to an increase in the AQP1 expression and a decrease in p-PKA-C, contributing to cartilage degradation. Conversely, anethole not only downregulated the AQP1 expression but also activated the PKA pathway, effectively suppressing cell inflammation and apoptosis. Furthermore, anethole also inhibited the enzymes responsible for cartilage degradation. In summary, our findings highlight the potential of anethole as a therapeutic agent for mitigating H2 O2 -induced inflammation and apoptosis in synovial cells, offering promising prospects for future RA treatments.

Naringin Induces ROS-Stimulated G1 Cell-Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma Cells.

Naringin, a bioflavonoid compound from grapefruit or citrus, exerts anticancer activities on cervical, thyroid, colon, brain, liver, lung, thyroid, and breast cancers. The present investigation addressed exploring the anticancer effects of naringin on nasopharyngeal carcinoma (NPC) cells. Naringin exhibits a cytotoxic effect on NPC-TW 039 and NPC-TW 076 cells with IC50 372/328 and 394/307 µM for 24 or 48 h, respectively, while causing little toxicity toward normal gingival epithelial (SG) cells (>500/500 µM). We established that naringin triggered G1 arrest is achieved by suppressing cyclin D1, cyclin A, and CDK2, and upregulating p21 protein in NPC cells. Exposure of NPC cells to naringin caused a series of events leading to apoptosis including morphology change (cell shrinkage and membrane blebbing) and chromatin condensation. Annexin V and PI staining indicated that naringin treatment promotes necrosis and late apoptosis in NPC cells. DiOC6 staining showed a decline in the mitochondrial membrane potential by naringin treatment, which was followed with cytochrome c release, Apaf-1/caspase-9/-3 activation, PARP cleavage, and EndoG expression in NPC cells. Naringin upregulated proapoptotic Bax and decreased antiapoptotic Bcl-xL expression, and dysregulated Bax/Bcl-xL ratio in NPC cells. Notably, naringin enhanced death receptor-related t-Bid expression. Furthermore, an increased Ca2+ release by naringin treatment which instigated endoplasmic reticulum stress-associated apoptosis through increased IRE1, ATF-6, GRP78, GADD153, and caspase-12 expression in NPC cells. In addition, naringin triggers ROS production, and inhibition of naringin-induced ROS generation by antioxidant N-acetylcysteine resulted in the prevention of G1 arrest and apoptosis in NPC cells. Naringin-induced ROS-mediated G1 arrest and mitochondrial-, death receptor-, and endoplasmic reticulum stress-mediated apoptosis may be a promising strategy for treating NPC.

Design, synthesis, and anticancer evaluation of 1-benzo[1,3]dioxol-5-yl-3-N-fused heteroaryl indoles.

A series of 1-benzo[1,3]dioxol-5-yl-indoles bearing 3-N-fused heteroaryl moieties have been designed based on literature reports of the activity of indoles against various cancer cell lines, synthesized via a Pd-catalyzed C-N cross-coupling, and evaluated for their anticancer activity against prostate (LNCaP), pancreatic (MIA PaCa-2), and acute lymphoblastic leukemia (CCRF-CEM) cancer cell lines. A detailed structure-activity relationship study culminated in the identification of 3-N-benzo[1,2,5]oxadiazole 17 and 3-N-2-methylquinoline 20, whose IC50 values ranged from 328 to 644 nM against CCRF-CEM and MIA PaCa-2. Further mechanistic studies revealed that 20 caused cell cycle arrest at the S phase and induced apoptosis in CCRF-CEM cancer cells. These 1-benzo[1,3]dioxol-5-yl-3-N-fused heteroaryl indoles may serve as a template for further optimization to afford more active analogs and develop a comprehensive understanding of the structure-activity relationships of indole anticancer molecules.

Calycosin alleviates H2 O2 -induced astrocyte injury by restricting oxidative stress through the Akt/Nrf2/HO-1 signaling pathway.

Oxidative stress-induced brain cell damage is a crucial factor in the pathogenesis of reactive oxygen species (ROS)-associated neurological diseases. Further, studies show that astrocytes are an important immunocompetent cell in the brain and play a potentially significant role in various neurological diseases. Therefore, elimination of ROS overproduction might be a potential strategy for preventing and treating neurological diseases. Accumulating evidence indicates that calycosin, a main active ingredient in the Chinese herbal medicine Huangqi (Radix Astragali Mongolici), is a potential therapeutic candidate with anti-inflammation and/or anticancer effects. Here, we investigated the protective effect of calycosin in brain astrocytes by mimicking in vitro oxidative stress using H2 O2 . The results revealed that H2 O2 significantly induced ROS and inflammatory factor (tumor necrosis factor [TNF]-α and interleukin [IL]-1ß) production, whereas post-treatment with calycosin dramatically and concentration-dependently suppressed H2 O2 -induced damage by enhancing cell viability, repressing ROS and inflammatory factor production, and increasing superoxide dismutase (SOD) expression. Additionally, we found that calycosin facilitated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and promoted its nuclear translocation, thereby inducing the expression of antioxidant molecules (heme oxygenase [HO]-1 and SOD) following H2 O2 treatment. Moreover, calycosin did not attenuated H2 O2 -induced astrocyte damage and ROS production in the presence of the ML385 (a Nrf2-specific inhibitor) and following Nrf2 silencing. Furthermore, calycosin failed to increase Akt phosphorylation and mitigate H2 O2 -induced astrocyte damage in the presence of the LY294002 (a selective phosphatidylinositol 3-kinase inhibitor), indicating that calycosin-mediated regulation of oxidative-stress homeostasis involved Akt/Nrf2/HO-1 signaling. These findings demonstrated that calycosin protects against oxidative injury in brain astrocytes by regulating oxidative stress through the AKT/Nrf2/HO-1 signaling pathway.

Synthesis and biological evaluation of N-glucosyl indole derivatives as sodium-dependent glucose co-transporter 2 inhibitors.

Sodium-dependent glucose co-transporter 2 (SGLT2) inhibition has been demonstrated to efficiently control hyperglycemia via an insulin secretion-independent pathway. The unique mode of action eliminates the risk of hypoglycemia and makes SGLT2 inhibitors an attractive option for the treatment of type 2 diabetes. In a continuation of our previous studies on SGLT2 inhibitors bearing different sugar moieties, sixteen new N-glucosyl indole derivatives were designed, synthesized, and evaluated for their inhibitory activity against hSGLT2. Of these sixteen, acethydrazide-containing N-glucosyl indole 9d was found to be the most potent SGLT2 inhibitor, and caused a significant elevation in urine glucose excretion in rats at 50 mg/kg, relative to the vehicle control.

E4BP4 inhibits AngII-induced apoptosis in H9c2 cardiomyoblasts by activating the PI3K-Akt pathway and promoting calcium uptake.

The bZIP transcription factor E4BP4 is a survival factor that is known to be elevated in diseased heart and promote cell survival. In this study the role of E4BP4 on angiotensin-II (AngII)-induced apoptosis has been examined in in vitro cell model. H9c2 cardiomyoblast cells that overexpressed E4BP4 were exposed to AngII to observe the cardio-protective effects of E4BP4 on hypertension related apoptosis. The results from TUNEL assays revealed that E4BP4 significantly attenuated AngII-induced apoptosis. Further analysis by Western blot and RT-PCR showed that E4BP4 inhibited AngII-induced IGF-II mRNA expression and cleavage of caspase-3 through the PI3K-Akt pathway. In addition, E4BP4 enhanced calcium reuptake into the sacroplasmic reticulum by down-regulating PP2A and by up-regulating the phosphorylation of PKA and PLB proteins. Our findings indicate that E4BP4 functions as a survival factor in cardiomyoblasts by inhibiting IGF-II transcription and by regulating calcium cycling.

Development of mussel-inspired 3D-printed poly (lactic acid) scaffold grafted with bone morphogenetic protein-2 for stimulating osteogenesis.

3D printing is a versatile technique widely applied in tissue engineering due to its ability to manufacture large quantities of scaffolds or constructs with various desired architectures. In this study, we demonstrated that poly (lactic acid) (PLA) scaffolds fabricated via fused deposition not only retained the original interconnected microporous architectures, the scaffolds also exhibited lower lactic acid dissolution as compared to the freeze-PLA scaffold. The 3D-printed scaffolds were then grafted with human bone morphogenetic protein-2 (BMP-2) via the actions of polydopamine (PDA) coatings. The loading and release rate of BMP-2 were monitored for a period of 35 days. Cellular behaviors and osteogenic activities of co-cultured human mesenchymal stem cells (hMSCs) were assessed to determine for efficacies of scaffolds. In addition, we demonstrated that our fabricated scaffolds were homogenously coated with PDA and well grafted with BMP-2 (219.1 ± 20.4 ng) when treated with 250 ng/mL of BMP-2 and 741.4 ± 127.3 ng when treated with 1000 ng/mL of BMP-2. This grafting enables BMP-2 to be released in a sustained profile. From the osteogenic assay, it was shown that the ALP activity and osteocalcin of hMSCs cultured on BMP-2/PDA/PLA were significantly higher when compared with PLA and PDA/PLA scaffolds. The methodology of PDA coating employed in this study can be used as a simple model to immobilize multiple growth factors onto different 3D-printed scaffold substrates. Therefore, there is potential for generation of scaffolds with different unique modifications with different capabilities in regulating physiochemical and biological properties for future applications in bone tissue engineering.

Stem cells rescue cardiomyopathy induced by P. gingivalis-LPS via miR-181b.

Systemic inflammation induced by bacterial infection is one of several causative agents for cardiovascular disorders in patients with periodontal disease. Experimental results indicate that miRNAs play important roles in systemic inflammation induced by endotoxins. Further evidence states that stem cell based therapy shows potential in the treatment of inflammatory responses induced by sepsis. This study investigates if stem cells show protective effects on cardiomyocyte damage induced by porphyromonas gingivalis-LPS (Pg-LPS) through regulating miRNAs. H9c2 cardiomyoblasts and neonatal rat cardiomyocytes (NRCMs) were damaged using Pg-LPS in this study. Pg-LPS damaged H9c2 or NRCMs were then rescued using adipose-derived stem cells (ADSC). The experimental results reveal that Pg-LPS treatment is capable of inducing TLR4/NFκB axis activation, cell death signaling and IGF1R/PI3 K/Akt axis suppression. miR181b was downregulated in Pg-LPS damaged H9c2/NRCMs. All markers were improved in H9c2/NRCMs cocultured with ADSC. miR181b mimic and inhibitor confirmed that miR181b plays a central role in regulating the cardio protective effect on Pg-LPS damaged H9c2/NRCMs cocultured with ADSC. miR181b acts as potential therapeutic marker in cardiomyopathy induced by Pg-LPS. Transplantation of adipose-derived stem cells show potential in the treatment of cardiomyopathy induced by porphyromonas gingivalis endotoxin via regulation of miR181b.

Mycotoxin Patulin Suppresses Innate Immune Responses by Mitochondrial Dysfunction and p62/Sequestosome-1-dependent Mitophagy.

Innate immune responses are important for pathogen elimination and adaptive immune response activation. However, excess inflammation may contribute to immunopathology and disease progression (e.g. inflammation-associated hepatocellular carcinoma). Immune modulation resulting from pattern recognition receptor-induced responses is a potential strategy for controlling immunopathology and related diseases. This study demonstrates that the mycotoxin patulin suppresses Toll-like receptor- and RIG-I/MAVS-dependent cytokine production through GSH depletion, mitochondrial dysfunction, the activation of p62-associated mitophagy, and p62-TRAF6 interaction. Blockade of autophagy restored the immunosuppressive activity of patulin, and pharmacological activation of p62-dependent mitophagy directly reduced RIG-I-like receptor-dependent inflammatory cytokine production. These results demonstrated that p62-dependent mitophagy has an immunosuppressive role to innate immune response and might serve as a potential immunomodulatory target for inflammation-associated diseases.

Dressing with epigallocatechin gallate nanoparticles for wound regeneration.

Several reagents have been studied to overcome the problems encountered with antiseptic use, such as moderate cutaneous wound cytotoxicity and skin thinning. We successfully prepared a gelatin/chitosan/epigallocatechin gallate nanoparticle incorporated in a poly(γ-glutamic acid)/gelatin hydrogel, which comprised activated carbon fibers with gentamicin, to fabricate a sandwiched dressing to enhance wound regeneration. The inner layer of activated carbon fibers with gentamicin was designed to prevent bacterial infection, and the outer layer of gelatin/chitosan/epigallocatechin gallate nanoparticles incorporated in a poly(γ-glutamic acid)/gelatin hydrogel was designed to prevent inflammation and facilitate reepithelialization. An in vitro study demonstrated that the dressing effectively inhibited target microorganisms, and scanning electron microscope and confocal laser scanning microscope indicated that the nanoparticles were homogeneously dispersed and migrated into the hydrogel. The in vivo study reported that the sandwiched dressing, comprising the poly(γ-glutamic acid)/gelatin hydrogel, was easy to remove from the wound and facilitated wound tissue regeneration and accelerated healing process.

N-Indolylglycosides bearing modifications at the glucose C6-position as sodium-dependent glucose co-transporter 2 inhibitors.

Suppression of glucose reabsorption through the inhibition of sodium-dependent glucose co-transporter 2 (SGLT2) is a promising therapeutic approach for the treatment of type 2 diabetes. To investigate the effect of C6-substitution on inhibition of SGLT2 by N-indolylglucosides, a small library of 6-triazole, 6-amide, 6-urea, and 6-thiourea N-indolylglycosides were synthesized and tested. A detailed structure-activity relationship (SAR) study culminated in the identification of 6-amide derivatives 6a and 6o as potent SGLT2 inhibitors, which were further tested for inhibitory activity against SGLT1. The data obtained indicated that 6a and 6o are mildly to moderately selective for SGLT2 over SGLT1. Both compounds were also evaluated in a urinary glucose excretion test and pharmacokinetic study; 6a was found capable of inducing urinary glucose excretion in normal SD rats.

Total Synthesis of the Naturally Occurring Glycosylflavone Aciculatin.

The new flavone-glycoside aciculatin (1), from Chrysopogon aciculatus, has been shown to have cytotoxic, anti-inflammatory, and antiarthritis activity. Further biological studies have been limited because of the limited availability of 1 from natural sources. Herein the first total synthesis of 1 in an overall yield of 8.3% is described. The synthesis involved the regio- and stereoselective glycosylation-Fries-type O-to-C rearrangement to construct the C-aryl glycosidic linkage, followed by a Baker-Venkataraman rearrangement and cyclodehydration to form the flavone scaffold.

Mitotic arrest induced in human DU145 prostate cancer cells in response to KHC-4 treatment.

In this study, the antitumor activity of KHC-4 was analyzed using human prostate cancer (CaP) cells and the underlining anticancer mechanisms of KHC-4 were identified. KHC-4 inhibited cell proliferation and induced cytotoxicity in the castration-resistant CaP DU145 cell line. The most effective concentration of KHC-4 was 0.1 µM. Cell cycle analysis demonstrated that KHC-4 treatment caused G2/M arrest and a subsequent increase in the sub-G1 population. Furthermore, KHC-4 is up-regulated p21, p27, and p53 in a time- and concentration-dependent manner. The exposure of cells to KHC-4 induced Cdk1/cyclin B1 complex activity, which led to cell cycle arrest. Moreover, KHC-4 inhibited the activities of MMP-2 and MMP-9 to inhibit tumor cell metastasis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1879-1887, 2016.

Effects of Different Concentrations of Collagenous Peptide from Fish Scales on Osteoblast Proliferation and Osteoclast Resorption.

The incidence of osteoporosis has increased among the elderly population. Establishing a model of bone remodeling for screening new drugs is critical to identify safe and effective treatments for osteoporosis. In this study, we established a platform to investigate the therapeutic effects of collagenous peptides extracted from scales of two kinds of fish, namely, sparidae and chanos. These peptides were prepared using seven concentrations of collagenous peptide: 100, 80, 60, 40, 20, 10 and 1 mg/ml. Experimental results indicated that collagenous peptides promoted the proliferation of osteoblasts and inhibited the proliferation of mature osteoclasts; the effective concentration of collagenous peptide-sparidae was 10 mg/ml and that of collagenous peptide-chanos was 40 mg/ml. These findings demonstrate that, to a certain extent, collagenous peptides extracted from fish scales can be used to prevent osteoporosis to assist bone remodeling.

Enhanced anti-cancer activity by curcumin-loaded hydrogel nanoparticle derived aggregates on A549 lung adenocarcinoma cells.

To investigate the anti-cancer activity of curcumin-loaded hydrogel nanoparticle derived aggregates on A549 lung adenocarcinoma cells. Curcumin was incorporated with biopolymeric chitosan, gelatin, and hyaluronan nanoparticles using an electrostatic field system. Characteristics of curcumin-loaded aggregates were examined including size and morphology, incorporation efficiency, stability and in vitro release. Treatment effect on A549 cells were assessed with cell viability assay, apoptosis assay, cell cycle analysis, reactive oxygen species detection, and Western blot. Observation from transmission electron microscopy show that the prepared biopolymeric nanoparticles were approximately 3-4 nm in diameter and that the size of the aggregates increased to approximately 26-55 nm after the incorporation of curcumin with the nanoparticles. The incorporation efficiency of curcumin into the chitosan, gelatin, and hyaluronan nanoparticles was 81, 67, and 78 % respectively. The formation of hyaluronan/curcumin and gelatin/curcumin aggregates seems to improve the stability of curcumin drug. The chitosan/curcumin aggregate has a faster release of curcumin than gelatin/curcumin and hyaluronan/curcumin aggregates. Treatment with chitosan/curcumin, gelatin/curcumin and hyaluronan/curcumin aggregates resulted in higher apoptosis rates of 45, 40 and 32 %, respectively, as compared to pure curcumin (less than 20 %) via Annexin V-FITC/PI analysis. Chitosan/curcumin aggregates induce the highest apoptosis effect (indicated by sub-G1 phase). In summary, chitosan/curcumin, gelatin/curcumin, and hyaluronan/curcumin aggregates represent higher anticancer proliferation properties in A549 cells than curcumin alone that exhibit great potential enhancement by either using fewer drugs or a decreased duration.

Lumbrokinase from earthworm extract ameliorates second-hand smoke-induced cardiac fibrosis.

Exposure to tobacco smoke has epidemiologically been linked to the occurrence of cardiovascular disease among nonsmokers but the associated molecular events are not well elucidated yet. When Sprague Dawley rats were exposed to second-hand tobacco cigarette smoke twice a day for a 30 days period at an exposure rate of 10 cigarettes/30 min, they showed adverse effects including reduced left ventricle weight, increased cardiac damages, deteriorated cardiac features, and cardiac fibrosis. Exposure to second-hand smoking (SHS) increased the molecular markers of cardiac fibrosis such as urokinase plasminogen activator and matrix metallopeptidases. The modulations in the protein levels were led by the activation of extracellular signal-regulated kinases (ERK1/2), the transcription factor-specificity protein 1 (SP1), and the fibrogenic master switch-connective for epithelial-mesenchymal transition tissue growth factor there by indicating their effective role in SHS-induced myocardial infraction. Dilong, an edible earthworm extract used in Chinese medicine and its bioactive fibrinolytic enzyme product-lumbrokinase, when administered in rats, restricted the SHS exposure induced cardiac fibrosis and provided cardio-protection. The results show that lumbrokinase and dilong administration can efficiently prevent epidemiological incidence of cardiac disease among SHS-exposed nonsmokers.

Earthworm (Pheretima aspergillum) extract stimulates osteoblast activity and inhibits osteoclast differentiation.

BACKGROUND: The potential benefits of earthworm (Pheretima aspergillum) for healing have received considerable attention recently. Osteoblast and osteoclast activities are very important in bone remodeling, which is crucial to repair bone injuries. This study investigated the effects of earthworm extract on bone cell activities. METHODS: Osteoblast-like MG-63 cells and RAW 264.7 macrophage cells were used for identifying the cellular effects of different concentrations of earthworm extract on osteoblasts and osteoclasts, respectively. The optimal concentration of earthworm extract was determined by mitochondrial colorimetric assay, alkaline phosphatase activity, matrix calcium deposition, Western blotting and tartrate-resistant acid phosphatase activity. RESULTS: Earthworm extract had a dose-dependent effect on bone cell activities. The most effective concentration of earthworm extract was 3 mg/ml, significantly increasing osteoblast proliferation and differentiation, matrix calcium deposition and the expression levels of alkaline phosphatase, osteopontin and osteocalcin. Conversely, 3 mg/ml earthworm extract significantly reduced the tartrate-resistant acid phosphatase activity of osteoclasts without altering cell viability. CONCLUSIONS: Earthworm extract has beneficial effects on bone cell cultures, indicating that earthworm extract is a potential agent for use in bone regeneration.

Recent progress in Glinus oppositifolius research.

CONTEXT: Glinus oppositifolius (L.) Aug. DC. (Molluginaceae), a perennial subshrubs herb, grows at low altitudes in the southern part of Taiwan, and is used in traditional Chinese medicine for herpes zoster and herpangina. OBJECTIVE: This study describes nutritional and therapeutic potential of Glinus oppositifolius and summarizes scientific evidence that supports traditional claims; recent progress in research for this plant is reviewed herein. MATERIALS AND METHODS: The literature has been retrieved from the web-based online systems including PubMed, Medline, and Google Scholar. The articles related to phytochemistry, pharmaceutical biology and ethnopharmacology have been excluded. RESULTS AND DISCUSSION: In clinical practice, the plant has been extensively investigated in a broad range of studies to provide scientific evidence for folklore claims or to find new therapeutic uses. The present review may arouse related research and make a more valid display for Taiwanese native medicinal plants.

Chlorogenic acid prevents ovariectomized-induced bone loss by facilitating osteoblast functions and suppressing osteoclast formation.

Osteoporosis is a usual bone disease in aging populations, principally in postmenopausal women. Anti-resorptive and anabolic drugs have been applied to prevent and cure osteoporosis and are associated to a different of adverse effects. Du-Zhong is usually applied in Traditional Chinese Medicine to strengthen bone, regulate bone metabolism, and treat osteoporosis. Chlorogenic acid is a major polyphenol in Du-Zhong. In the current study, chlorogenic acid was found to enhance osteoblast proliferation and differentiation. Chlorogenic acid also inhibits the RANKL-induced osteoclastogenesis. Notably, ovariectomy significantly decreased bone volume and mechanical properties in the ovariectomized (OVX) rats. Administration of chlorogenic acid antagonized OVX-induced bone loss. Taken together, chlorogenic acid seems to be a hopeful molecule for the development of novel anti-osteoporosis treatment.

Incense-burning smoke ingredient Auramine enhances lincRNA-p21 expression for chemosensitization in p53-mutated non-small cell lung cancer.

Incense-burning smoke is a deleterious air pollutant that initiates cytotoxic effects by inducing apoptosis in lung epithelial cells and also acts as a risk factor for lung cancers. Auramine, an ingredient of incense smoke, has been implicated in tumor progression and cellular sensitivity in non-small cell lung cancer (NSCLC) towards anti-cancer agents through unclear mechanisms. Tumor protein p53 (TP53)-activated long intergenic non-coding RNA-p21 (lincRNA-p21) undertakes a pivotal role in regulating cell apoptosis and chemosensitivity. TP53 mutations prevalent in 50% of NSCLC, contribute to diminished therapeutic efficacy. However, the influence of auramine on chemotherapy-induced lincRNA-p21 expression and apoptosis in NSCLC with different TP53 genetic statuses remains unexplored. This study disclosed that both wild-type p53 (wtp53) and mutant p53 (mutp53) mediate lincRNA-p21 expression, albeit through distinct promoter enhancers, p53-response element (p53RE) and non-B DNA structure G-quadruplex (GQ), respectively. Intriguingly, auramine functions as an effective stabilizer of the GQ structure, augmenting mutp53-mediated lincRNA-p21 expression and enhancing apoptosis and cellular sensitivity to chemotherapy in mutp53-expressing NSCLC cells. These findings suggest a mechanism by which mutp53, in the presence of auramine, is endowed with tumor-suppressing function akin to wtp53, thereby aiding in combating chemoresistance in NSCLC cells harboring TP53 mutations.