Significant Anticancer Activity Research Articles

Rare Sesterterpenoids from the Soil Derived Fungus, Aspergillus variecolor Strain SDG, Therapeutic Potential of Stellatic Acid and Docking Studies

Ethyl acetate extract of the cultures of the soil‐derived filamentous fungus, Aspergillus variecolor SDG strain from Nallamala forest resulted in the isolation of extremely rare sesterterpenoids, stellatic acid (1) and andilesin C (2). We report a thorough chemical characterization of these compounds using various spectroscopic techniques and evaluation of their in vitro preclinical therapeutic potential. Stellatic acid exhibits potent antioxidant activity with an IC50 of 38 µg/mL and significant anticancer activity against HeLa, HepG2, MCF7, and A549 cancer cell lines with an IC50 of 7‐12 µM. On the other hand, andilesin C displayed moderate cytotoxicity against DU145 and B16F10 cancer cell lines but lacked antioxidant activity. Furthermore, the potential hypoglycemic property of stellatic acid was evaluated by measuring its inhibitory effect against α‐glucosidase. It exhibited tenfold potency against yeast α‐glucosidase (IC50 101.73 µg/mL) than mammalian α‐glucosidase (IC50 1000.00 µg/mL). Docking studies were also performed to suggest the interaction mode of stellatic acid in the α‐glucosidase enzyme active site. Notably, yeast α‐glucosidase shows a higher affinity towards stellatic acid than mammalian α‐glucosidase (3TOP). Thus, the in vitro preclinical study of stellatic acid suggests its potential efficacy in therapeutic drug development.

Amide Functionalized Novel Pyrrolo-pyrimidine Derivative as Anticancer Agents: Synthesis, Characterization and Molecular Docking Studies.

The development of new therapies targeting crucial kinases involved in cancer progression is a promising area of research. Pyrazolo pyrimidine derivatives have emerged as potential candidates for this purpose. This study aims to synthesize pyrazolo pyrimidine derivatives (5a-5r), evaluate their molecular docking against key kinases, and assess their anticancer activity. The synthesis involved a multi-step procedure starting with the cyclization of 6-amino-2- methylpyrimidin-4(3H)-one (1) to form 2-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-4-ol (2). This was followed by chlorination to yield 4-chloro-2-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine (3) and nucleophilic substitution to produce 2-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-4-amine (4). The final derivatives (5a-5r) were synthesized through amide bond formation with various carboxylic acids using DCC and DMAP. Structural elucidation was confirmed via NMR, mass spectrometry, and HRMS. Molecular docking studies were conducted against Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), and cyclin-dependent kinase 4 (CDK4). Anticancer activity was evaluated against MCF-7, SET-2, and HCT-116 cell lines. Structural elucidation confirmed the successful synthesis of the derivatives. Molecular docking studies revealed promising binding affinities for selected derivatives, particularly those with heterocyclic substitutions. Anticancer activity evaluation showed diverse potency profiles, with several derivatives demonstrating IC50 values comparable to the reference drug, doxorubicin. Derivatives featuring nitro and heterocyclic moieties exhibited significant anticancer activity. The synthesized pyrazolo pyrimidine derivatives showed potential as lead compounds for further development due to their promising binding affinities and significant anticancer activity, particularly those with nitro and heterocyclic moieties.

In vitro and computational investigation of antioxidant and anticancer properties of Streptomyces coeruleofuscus SCJ extract on MDA-MB-468 triple-negative breast cancer cells

This study aimed to explore the antioxidant potential of the ethyl acetate extract of Streptomyces coeruleofuscus SCJ strain, along with its inhibitory effects on the triple-negative human breast carcinoma cell line (MDA-MB-468). The ethyl acetate extract’s total phenolic and flavonoid contents were quantified, and its antioxidant activity was investigated using DPPH (1,1-Diphenyl-2-picrylhydrazyl), ABTS (2,2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid), and FRAP (Ferric Reducing Antioxidant Power) assays. Furthermore, the cytotoxic effect of the organic extract from Streptomyces coeruleofuscus SCJ on MDA-MB-468 cancer cells was assessed via the crystal violet assay. In tandem, a thorough computational investigation was conducted to explore the pharmacokinetic properties of the identified components of the extract, utilizing the SwissADME and pKCSM web servers. Additionally, the molecular interactions between these components and Estrogen Receptor Beta, identified as a potential target, were probed through molecular docking studies. The results revealed that ethyl acetate extract of SCJ strain exhibited remarkable antioxidant activity, with 39.899 ± 1.56% and 35.798 ± 0.082% scavenging activities against DPPH and ABTS, respectively, at 1 mg/mL. The extract also displayed significant ferric reducing power, with a concentration of 1.087 ± 0.026 mg ascorbic acid equivalents per mg of dry extract. Furthermore, a strong positive correlation (p < 0.0001) between the antioxidant activity, the polyphenol and the flavonoid contents. Regarding anticancer activity, the SCJ strain extract demonstrated significant anticancer activity against TNBC MDA-MB-468 cancer cells, with an inhibition percentage of 62.76 ± 0.62%, 62.67 ± 0.93%, and 58.07 ± 4.82% at 25, 50, and 100 µg/mL of the extract, respectively. The HPLC-UV/vis analysis revealed nine phenolic compounds: gallic acid, sinapic acid, p-coumaric acid, cinnamic acid, trans-fereulic acid, syringic acid, chloroqenic acid, ellagic acid, epicatechin. Streptomyces coeruleofuscus SCJ showed promise for drug discovery, exhibiting antioxidant and anticancer effects.

Dibenzoxanthene-β-lactam hybrids as potential antioxidant and anticancer agents: Synthesis, biological evaluation, and docking study

In this study, we designed and synthesized a series of β-lactam compounds bearing 14-phenyl-14H-dibenzo[a,j]xanthene moiety attached to the N-1 position of the β-lactam ring through a [2 + 2] cycloaddition process. All the synthesized compounds have been characterized by elemental analysis, Fourier-transform infrared (FT-IR) and nuclear magnetic resonance (1H NMR and 13C NMR) spectral analysis. These derivatives were evaluated for their anticancer and antioxidant activities. The in vitro anticancer activity of new compounds was examined against MCF-7 (breast cancer), HepG2 (liver hepatocellular carcinoma), and TC-1 (mouse lung epithelial) cell lines by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Notably, compounds 4c, 4e and 4 g demonstrated significant anticancer activity against TC-1 cell line. Additionally, compounds 4c, 4f and 4 g exhibited promising levels of efficacy against the MCF-7 cell line. The diphenylpicrylhydrazyl (DPPH) radical scavenging assay indicated that 4h and 4i are more potent antioxidant agents than the Vitamin C, while 4a, 4b, 4c, and 4j exhibited moderate antioxidant capabilities. Furthermore, the docking simulations are consistent with the biological assay results, indicating that the hybrids may bind to protein targets through hydrogen bonding and other nonvalent interactions.

A novel approach for the treatment of AML, through GHRH antagonism: MIA-602.

Acute myeloid leukemia (AML) is the most aggressive and prevalent form of leukemia in adults. The gold-standard intervention revolves around the use of chemotherapy, and in some cases hematopoietic stem cell transplantation. Drug resistance is a frequent complication resulting from treatment, as it stands there are limited clinical measures available for refractory AML besides palliative care. The goal of this review is to renew interest in a novel targeted hormone therapy in the treatment of AML utilizing growth hormone-releasing hormone (GHRH) antagonism, given it may provide a potential solution for current barriers to achieving complete remission post-therapy. Recapitulating pre-clinical evidence, GHRH antagonists (GHRH-Ant) have significant anti-cancer activity across experimental human AML cell lines in vitro and in vivo and demonstrate significant inhibition of cancer in drug resistant analogs of leukemic cell lines as well. GHRH-Ant act in manners that are orthogonal to anthracyclines and when administered in combination synergize to produce a more potent anti-neoplastic effect. Considering the adversities associated with standard AML therapies and the developing issue of drug resistance, MIA-602 represents a novel approach worth further investigation.

Synthesis of chlorotoxin functionalized metallic nanoparticles and their in vitro evaluation of cytotoxic effects in nervous system cancer cell lines

The treatment of glioblastoma (GB) and neuroblastoma (NB) remains a challenge, as current chemotherapies are plagued with systemic toxicity, drug resistance, and inadequate blood–brain barrier (BBB) penetration. Therefore, novel therapeutic strategies with high specificity and the capacity to bypass the BBB are required. Chlorotoxin (CTX) selectively targets gliomas and neuroectodermal tumors, hence the use of CTX-targeted nanoparticles (NPs) represents a promising therapeutic approach for nervous system (NS) cancers. Bimetallic NPs composed of two metals such as gold-platinum NPs (AuPtNPs) exhibit enhanced anticancer properties compared to single-metal NPs, however their application in studying NS tumors has been relatively limited. CTX-functionalized monometallic gold NPs (CTX-AuNPs) and bimetallic gold-platinum NPs (CTX-AuPtNPs) were synthesized in this study. The NPs were characterized by Ultraviolet-Visible Spectroscopy (UV–vis), Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) and Fourier Transform Infra-Red Spectroscopy (FTIR). Cytotoxicity of NPs was investigated in cancer (U87 and SH-SY5Y) and non-cancer (KMST-6) cells using the water-soluble tetrazolium (WST)-1 assay. The CTX-AuNPs and CTX-AuPtNPs had a core size of ∼5 nm. The CTX-AuPtNPs showed significant anticancer activity in U87 cells possibly due to the synergistic effects of combined metals. Findings obtained from this study demonstrated that CTX can be used to target NS cancers and that bimetallic NPs could be effective in their treatment. More studies are required to investigate the mechanisms of NPs toxicity, and further explore the hyperthermia treatment of NS cancer using the CTX-AuPtNPs.

Effect of crude ethanolic seed extract from Mucuna pruriens on proliferation, apoptosis, and cell cycle arrest in gastric adenocarcinoma (AGS) cells

Abstract Background Gastric cancer is a prevalent form of malignancy among many common carcinoma cases globally. This study was designed to assess the anticancer potential of the crude ethanolic seed extract from Mucuna pruriens against the gastric cancer cell line (AGS). Various assays were employed to assess the anticancer properties, including examinations of cell viability, nuclear morphology, apoptosis using AO/EB staining, changes in mitochondrial membrane potential, lactate dehydrogenase activity, DNA fragmentation, and cell cycle arrest. Results The crude extract exhibited significant anticancer activity against the human gastric cancer cell line (AGS), as determined by the MTT assay, with an inhibition concentration (IC50) of 600 µg/mL at 24 h. Distinct cellular and nuclear morphological changes were observed with different concentrations of crude ethanolic seed extract. The LDH release assay reveals cell death in AGS cells, as evidenced by a significant increase in the release of LDH enzyme. DNA fragmentation analysis and flow cytometry results indicate that the extract induces chromatin condensation, apoptotic cell death, and cell cycle arrest at the G0/G1 phase in the AGS cancer cell line. These results highlight the potential therapeutic advantages of Mucuna pruriens seed extract against gastric cancer cells. Conclusion This study could pave the way for identifying diverse natural bioactive compounds sourced from Mucuna pruriens seed, leading to the development of novel drug with potential anticancer properties.

Green Synthesis of Dracocephalum kotschyi-Coated Silver Nanoparticles: Antimicrobial, Antioxidant, and Anticancer Potentials.

BACKGROUND The environmentally friendly production of silver nanoparticles (AgNPs) has gained significant attention as a sustainable alternative to traditional chemical methods. This study focused on synthesizing AgNPs using extract of Dracocephalum kotschyi (D. kotschyi), a medicinal plant. MATERIAL AND METHODS The biosynthesis of AgNPs was monitored using UV-visible spectrophotometry. The role of phytoconstituents from D. kotschyi in stabilizing AgNPs was analyzed using Fourier-transform infrared (FTIR) spectroscopy. Dynamic light scattering (DLS) spectroscopy was used to determine the size, charge, and polydispersity of the nanoparticles, while scanning electron microscopy (SEM) was employed to assess their morphology. We evaluated the antimicrobial efficacy of the synthesized AgNPs against various bacteria, their antioxidant properties via a 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay, and their cytotoxic activity against the HeLa cervical cancer cell line. RESULTS The formation of AgNPs was indicated by a color change and the emergence of a surface plasmon resonance peak at 418 nm. The nanoparticles demonstrated significant antimicrobial, antioxidant, cytotoxic, and anticancer activities. Morphology, size, and shape analysis revealed nearly spherical particles with an average size of 43 nm. FTIR confirmed the presence of phenolic compounds in the extract, serving as reducing and capping agents. X-ray diffraction (XRD) analysis confirmed the crystalline structure of the nanoparticles. Antimicrobial assessments showed effectiveness against Escherichia coli and Staphylococcus aureus. The DPPH scavenging assay demonstrated efficient antioxidant activity, and potent apoptotic anticancer effects were observed on cervical cancer cells. CONCLUSIONS The extract of D. kotschyi was effective as a reducing agent in the environmentally friendly synthesis of AgNPs, which exhibited noteworthy antimicrobial, antioxidant, and anticancer properties. These findings suggest potential biomedical applications for the synthesized AgNPs.

A Novel Phytocolorant, Neoxanthin, as a Potent Chemopreventive: Current Progress and Future Prospects.

Cancer is a general term for a group of similar diseases. It is a combined process that results from an accumulation of abnormalities at different biological levels, which involves changes at both genetic and biochemical levels in the cells. Several modifiable risk factors for each type of cancer include heredity, age, and institutional screening guidelines, including colonoscopy, mammograms, prostate-specific antigen testing, etc., which an individual cannot modify. Although a wide range of resources is available for cancer drugs and developmental studies, the cases are supposed to increase by about 70% in the next two decades due to environmental factors commonly driven by the way of living. The drugs used in cancer prevention are not entirely safe, have potential side effects and are generally unsuitable owing to substantial monetary costs. Interventions during the initiation and progression of cancer can prevent, diminish, or stop the transformation of healthy cells on the way to malignancy. Diet modifications are one of the most promising lifestyle changes that can decrease the threat of cancer development by nearly 40%. Neoxanthin is a xanthophyll pigment found in many microalgae and macroalgae, having significant anti-cancer, antioxidant and chemo-preventive activity. In this review, we have focused on the anti-cancer activity of neoxanthin on different cell lines and its cancer-preventive activity concerning obesity and oxidative stress. In addition to this, the preclinical studies and future perspectives are also discussed in this review.

Synthesis of Luminescent Copper Nanoparticles Using Couroupita guianensis Flower Extract: Evaluation of Antibacterial and Anticancer Activities.

The biosynthesis of nanoparticles is a crucial research area aimed at developing innovative, cost-effective, and eco-friendly synthesis techniques for various applications. Herein, we synthesized copper oxide nanoparticles (CuNPs) using Couroupita guianensis flower extract via a simple green synthesis method. These green CuNPs demonstrate promising antimicrobial activity and anticancer activity against A549 nonsmall cell lung cancer (NSCLC) cells. We comprehensively characterized the CuNPs using UV spectrum, XRD, FTIR, SEM, and EDS analyses. The antibacterial and anticancerous performance is attributed to their spherical-like morphology, which enhances effective interaction with bacterial and cancer cells. Moreover, CuNPs proved effective in inactivating Escherichia coli, achieving 2%, 52%, and 99% inactivation at 0, 30, and 60 min, respectively, and Listeria monocytogenes, achieving 1%, 48%, and 98% inactivation at 0, 30, and 60 min, respectively, under visible light. Furthermore, the CuNPs exhibited significant anticancer activity against A549 NSCLC cells, achieving cell viability reductions of 10%, 30%, 50%, 70%, 83%, and 91% at concentrations of 25, 50, 100, 150, 200, and 250 μg/mL, respectively. The green synthesized CuNPs demonstrate their potential in biomedical applications.

Anticancer, Anti-inflammatory, and Neuroprotective Effect of Oleocanthal from Virgin Olive Oil – A Review

Background: Oleocanthal (OC), a phenolic compound found in extra virgin olive oil (EVOO), is renowned for its bioactive properties, including anti-inflammatory, anticancer, and neuroprotective effects. OC has been shown to inhibit the growth of various cancer cells, such as colon, breast, liver, and melanoma. Additionally, its potential role in neuroprotection, particularly in Alzheimer's disease, has been extensively researched. Methods: A comprehensive literature review was conducted to evaluate the pharmacokinetics, dynamics, and therapeutic mechanisms of OC. Databases such as PubMed, SCOPUS, and Web of Science were used to identify studies on OC’s therapeutic effects, particularly in cancer, Alzheimer's disease, inflammation, and microbial infections. Results: OC demonstrated potent anti-inflammatory effects by inhibiting cyclooxygenase (COX) enzymes and reducing pro-inflammatory signaling molecules. It also showed significant anticancer activity by modulating pathways like the apoptotic and HGF/c-Met pathways. In Alzheimer's disease, OC reduced astrocyte inflammation and promoted the clearance of amyloid beta proteins, supporting its neuroprotective role. Moreover, OC exhibited antimicrobial and antioxidant properties, further contributing to its therapeutic potential. Conclusion: Oleocanthal exhibits promising therapeutic effects across a range of diseases, including cancer and neurodegenerative disorders. However, while its in vitro pharmacological properties are well-established, further in vivo studies are needed to fully understand its potential as a medicinal agent. The findings of this review underscore OC’s potential to serve as a therapeutic lead molecule for a variety of conditions.

Synthesis and SAR Studies of Some Novel Series of Pyrimidine Analogues

A series of novel ethyl-4-methyl-6-phenyl-2-(substituted thio)pyrimidine-5-carboxylate (4a-m), ethyl-4-methyl-phenyl-2-(substituted sulfinyl)pyrimidine-5-carboxylate (5a-m) and ethyl-4-methyl-phenyl-2-(substituted sulfonyl)pyrimidine-5-carboxylate (6a-m) were synthesized by multi-step organic synthesis. The synthesized compounds were characterized by 1H NMR, 13C NMR, LCMS and elemental analysis. Most of the compounds showed significant antibacterial and anticancer activity comparable to or higher than the standard employed.

Anti-cancer activity of brucine loaded Cu(OH)2/ZnO nanoparticles against chronic myeloid leukemia cell line (K562) via apoptotic signaling pathway

Background and objectiveChronic myeloid leukemia (CML) is marked by abnormal blood cell production and traditional treatments often cause severe side effects and resistance. This study improves cancer therapy by using copper (II) hydroxide (Cu(OH)₂) and zinc oxide (ZnO) nanoparticles combined with brucine (Bru) to enhance targeted drug delivery and efficacy. Materials and methodsBru-Cu(OH)₂-ZnO NPs were synthesized and characterized using various analytical techniques. Their cytotoxicity was evaluated on K562 myeloid leukemia cells through cell viability assays, dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining, and measurement of oxidative stress indicators such as nitric oxide and lipid peroxidation levels. Antioxidant activity was assessed by glutathione (GSH) levels, while apoptosis was investigated via Caspase 3 and 9 activity and gene expression analysis (Bax, p53, and Bcl-2) using real-time polymerase chain reaction (RT-PCR). ResultsThe novel Bru-Cu(OH)₂-ZnO NPs demonstrated significant anti-cancer activity by markedly reducing K562 cell viability and enhancing cytotoxicity in a dose-dependent manner. These nanoparticles effectively scavenged free radicals, increased lipid peroxidation and nitric oxide levels, and improved caspase activity. Notably, gene expression analysis revealed that Bru-Cu(OH)₂-ZnO NPs led to overexpression of pro-apoptotic genes (Bax and p53) and downregulation of the anti-apoptotic gene (Bcl-2), highlighting their potential as effective cancer therapeutics. ConclusionThe synthesized Bru-Cu(OH)2-ZnO NPs shown excellent anti-cancer efficacy against the K562 cell line. This study underscores the potential of combining bioactive compounds with metal oxide nanoparticles to enhance targeted drug delivery and therapeutic effectiveness, offering a promising approach for advancing cancer treatment.

Novel Tubeimoside I liposomal drug delivery system in combination with gemcitabine for the treatment of pancreatic cancer.

Aim: To evaluate the anti-pancreatic cancer effect of novel Tubeimoside I multifunctional liposomes combined with gemcitabine.Methods: Liposomes were prepared through the thin film hydration method, with evaluations conducted on parameters including encapsulation efficiency (EE%), particle size, polydispersity index (PDI), zeta potential (ZP), storage stability, and release over a 7-day period. The cellular uptake rate, therapeutic efficacy in vitro and in vivo and the role of immune microenvironment modulation were evaluated.Results: The novel Tubeimoside I multifunctional liposomal exhibited good stability, significant anti-cancer activity, and immune microenvironment remodeling effects. Furthermore, it showed a safety profile.Conclusion: This study underscores the potential of Novel Tubeimoside I multifunctional liposomal as a promising treatment option for pancreatic cancer.

Design, synthesis, characterization, and biological activities of novel Ag(I)-NHC complexes based on 1,3-dioxane ligand

Herein, a series of new Ag(I)-NHC complexes containing 1,3-dioxane group were synthesized by the direct reaction of Ag2O and benzimidazolium salts in light-free conditions. All Ag(I)-NHC complexes were spectrally characterized using 1H, 13C NMR, FT-IR, LC-MS, and elemental analysis. Additionally, the structures of compounds 1a and 1e were elucidated by the single X-ray diffraction techniques. Further, the synthesized Ag(I)-NHC complexes were evaluated for cytotoxicity study on the L-929 cells and the anticancer activity against the HCT 116 and MCF-7 cancer cell lines. Notably, 1a showed significant anticancer activity against HCT 116 with an IC50 of 6.37 ± 0.92 μg/mL compared to cisplatin (IC50 = 36.75 ± 1.76 μg/mL). 1c (IC50 = 3.21 ± 1.96 μg/mL) and 1e (IC50 = 3.72 ± 1.12 μg/mL) exhibited significant anticancer activity against MCF-7 cells and was similar to cisplatin (IC50 = 32.17 ± 2.85 μg/mL). Meanwhile, 1a and 1e displayed the highest selectivity index. Most importantly, the cell viability test showed that 1e induced neglectable cytotoxicity (IC50 = 36.38 ± 2.27 μg/mL) toward L-929 and was similar to cisplatin (IC50 = 36.11 ± 2.09 μg/mL). The anticancer activities of Ag(I)-NHC complexes vary depending on the substituent group of the silver complex and the cell line type. Moreover, the inhibitory mechanism of 1e was not dependent on caspase-associated apoptosis initiated by the lysosomal-mitochondrial pathway. Taken together, we conclude that this work provides a simple and rapid protocol for the synthesis of Ag(I)-NHC complexes and the featured Ag(I)-NHC complexes have an anticancer drug potential for biomedical applications.

S. glabra exerts anti-lung cancer effects by inducing ferroptosis and anticancer immunity

BackgroundSarcandra glabra (S. glabra), a traditional Chinese medicine (TCM), has demonstrated significant anticancer activity; however, the underlying mechanisms have not yet been fully elucidated. PurposeThis study aimed to investigate the effects of S. glabra on lung cancer and to explore its underlying mechanisms. MethodsThe chemical profile of S. glabra was analyzed via ultrahigh-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). The effects of S. glabra on the viability, proliferation, apoptosis, migration, and invasion of lung cancer cells were assessed via CCK8, colony formation, flow cytometry, scratch, and Transwell assays. In vivo anticancer activity was evaluated in an LLC mouse model. Proteomic analysis was performed to identify key molecules and pathways in S. glabra-treated LLC cells. The expression of ferroptotic proteins and associated cellular events were examined via western blotting, ROS production, iron accumulation, and lipid peroxidation assays. Immune modulation in tumor-bearing mice was evaluated by detecting immune cells and cytokines in the peripheral blood and tumor tissue. ResultsOur analysis quantified 1997 chemical markers in S. glabra aqueous extracts. S. glabra inhibited the viability and proliferation of lung cancer cells and induced cell cycle arrest and apoptosis. Scratch and Transwell assays demonstrated that S. glabra suppressed the migration and invasion of lung cancer cells. Oral administration of S. glabra significantly inhibited tumor growth in LLC tumor-bearing mice. Proteomic analysis revealed that S. glabra upregulated the expression of the HMOX1 protein and activated the ferroptosis pathway. Consistent with these findings, we found that S. glabra triggered ferroptosis in lung cancer cells, as evidenced by the upregulation of HMOX1, downregulation of GPX4 and ferritin light chain proteins, iron accumulation, increased ROS production, and lipid peroxidation. Furthermore, S. glabra demonstrated immunostimulatory properties in LLC tumor-bearing mice, leading to increased populations of immune cells (NK cells) and elevated cytokine levels (IL-2). ConclusionThis study is the first to demonstrate that S. glabra induces ferroptosis in lung cancer cells by regulating HMOX1, GPX4, and FTL. These findings provide a robust scientific basis for the clinical application of S. glabra in lung cancer treatment.

METABOLIC SYNDROME: IN VITROANTIOXIDANT, ANTICANCER, ANTI-INFLAMMATORY AND ANTIMICROBIAL ACTIVITIES OF DISSOTIS ROTUNDIFOLIA(SM.) WITH PHYTOCHEMICAL AND NUTRITIONAL COMPONENTS

Background:Dissotis rotundifolia(Sm.) Triana isa prostrate herb of the family Melastomataceae. It is used for the treatment of obesity, hypertension, circulatory problems and metabolic syndrome (MS). This study evaluated the antioxidant, anticancer, anti-inflammatory.and antimicrobial activities of the whole plant of D. rotundifoliato validateits therapeutic potential in the management and treatment of MS. Materials and Methods: The plant was screened for proximate, mineral, vitamin and phytochemical components, as well as antioxidant activities using standard laboratory techniques. The anticancer activities of the ethanol plant extract were against kidney (VERO) and breast (MCF-7) cancer cells. The anti-inflammatory activity of the extract was determined using nitric oxide production inhibition assay and the antimicrobial activity was evaluated against five pathogenic organisms. All data were subjected to statistical analysis. Results: The plant was rich in carbohydrate (47.87%), protein (22.5%), crude fibre (9.57%), Na (206.67 mg/100 g), Ca (183.33mg/100 g), vitamin C (25.53 mg/100 g), flavonoids (685.00 mg/100 g), alkaloids (616.67 mg/100 g) and saponins (471.67 mg/100 g) contents. Theextract exhibited considerableand variedantioxidant activities.The plant extract was very active against VERO and MCF-7 cellsatlow concentrations(0.145 mg/ml and 0.141 mg/ml respectively) compared to doxorubicin. It also exhibited significant anti-inflammatory action against lipopolysaccharide (LPS)-stimulated RAW macrophage. The extract was active against all test organisms. Overall, D. rotundifolia displayed significant antioxidant, anticancer, anti-inflammatory and antimicrobial activities. Conclusion: The observed bioactivities of the plant could be attributed to its phytocontents and are indications of itspotential as an agent for the managementand treatment ofmetabolic syndrome.

Anti-Lung Cancer and Cell Migration Inhibition Properties of Ethyl Acetate Extract of Selaginella doederleinii Towards HTB-183 Cells through In Silico and In Vitro Approach

Continuous research and development to obtain novel anti-lung cancer agents is essential, considering the high prevalence and mortality of the disease. The biflavonoid compounds of Selaginella doederleinii showed significant anticancer activities. This study aims to determine the cytotoxic and cell migration inhibition properties of ethyl acetate extract of Selaginella doederleinii (EAESD) against HTB-183 cells through in silico and in vitro methods. This study started with extraction and then identified biflavonoids in EAESD by HPLC. In vitro analysis was conducted through MTT Assay to observe the cytotoxic properties of EAESD and Wound Scratch Healing Assay to observe its cell migration inhibitory properties. In silico studies to obtain the potential anti-lung cancer compounds and their protein targets were conducted through bioinformatics, combining PASS analysis, Swiss Target Prediction, and STITCH. The obtained compounds and protein targets were analyzed in Molecular Docking to evaluate the binding affinities. The result showed that EAESD contained biflavonoid compounds, exhibited cytotoxic activity with an IC50 value of 190 μg/ml, and inhibited the migration rate of HTB-183 cells. Based on in silico analysis, the three biflavonoids with the highest potential of antilung cancer activity along with their target protein are robustaflavone 7,4-dimethyl ether with EGFR, heveaflavone with ESR1, and 7,4',7'',4'''-tetra-O-methyl-amentoflavonewith TNF. All compounds can bind to each protein target with the docking score -9.2 kcal/mol, -9.5 kcal/mol, and -6.5 kcal/mol, respectively. This study suggested preliminary data regarding the potential of Selaginella doederleinii to inhibit the proliferation and migration of the HTB-183 cell line of lung cancer.Keywords: Selaginella doederleinii, HTB-183, cytotoxicity, cell migration, in silico analysis.

Polyphyllin I exerts anti-hepatocellular carcinoma activity by targeting ZBTB16 to activate the PPARγ/RXRα signaling pathway

BackgroundStudies have reported that polyphyllin I (PPI) had effective anti-tumor activity against hepatocellular carcinoma (HCC). However, the precise molecular mechanism of this action and the direct target remain unclear. The aim of this study was to discover the molecular targets and the exact mechanism of PPI in the treatment of HCC.MethodsVarious HCC cells and Zebrafish xenotransplantation models were used to examine the efficacy of PPI against HCC. A proteome microarray, surface plasmon resonance (SPR) analysis, small molecule transfection, and molecular docking were conducted to confirm the direct binding targets of PPI. Transcriptome and Western blotting were then used to determine the exact responding mechanism. Finally, the anticancer effect and its precise mechanism, as well as the safety of PPI, were verified using a mouse tumor xenograft study.ResultsThe results demonstrated that PPI had significant anticancer activity against HCC in both in vitro studies of two cells and the zebrafish model. Notably, PPI selectively enhanced the action of the Zinc finger and BTB domain-containing 16 (ZBTB16) protein by directly binding to it. Furthermore, specific knockdown of ZBTB16 markedly attenuated PPI-dependent inhibition of HCC cell proliferation and migration caused by overexpression of the gene. The transcriptome and Western blotting also confirmed that the interaction between ZBTB16 and PPI also activated the PPARγ/RXRα pathway. Finally, the mouse experiments confirmed the efficacy and safety of PPI to treat HCC.ConclusionsOur results indicate that ZBTB16 is a promising drug target for HCC and that PPI as a potent ZBTB16 agonist has potential as a therapeutic agent against HCC by regulating the ZBTB16/PPARγ/RXRα signaling axis.

Chemical composition and bioactivity of Codium dwarkense collected from the earthquake crack region of Ras Muhammad National Park, Red Sea, Egypt

Ras Muhammad National Park, located at the southern tip of the Sinai Peninsula, Egypt, is well-known for its unique marine biodiversity. One interesting region of the park is the Earthquake Crack, a tidal-influenced inland cave formed by a 1968 earthquake, that known for its rich seaweed community, with dominance of Codium dwarkense. This study evaluates the bioactive compounds and bioactivities of C. dwarkense from the crack region. The sample were collected, processed, and assessed for hydrographic parameters, nutritional composition, minerals, bioactive compounds, and bioactivity. Results showed high levels of carbohydrates and significant mineral content, with potassium and calcium being predominant. C. dwarkense also showed considerable amounts of vitamin C (32.4 mg/100g), vitamin E (400 mg/100g), phenolics (250.08 mg GAE/g), and flavonoids (85.4 mg rutin/g). The HPLC profile was dominated with quercetin, apigenin, pyrogallol, zeaxanthin, and benzoic acid. The GC-MS analyses identified several fatty acids, which were dominated with Hexadecanoic acid and Oleic acid. Bioactivity assays demonstrated significant antimicrobial, antioxidant, antidiabetic, anti-inflammatory, and anticancer activities. This study highlights the influence of the unique features of the Earthquake Crack region on C. dwarkense ability to produce valuable bioactive compounds with diverse health benefits. These findings contribute to the recognition of C. dwarkense as a functional food and nutraceutical resource.