Anticancer Properties Research Articles

Designed Synthesis of Amino-Azo-Quinoline and Their Nickel(II) Complexes: Molecular Structure, Electrochemistry and an Insight Into Their In Vitro Anti-Cancer Activities.

Amino-quinolines are potential candidates that may provide some insight into the current chemotherapeutic research due to their demonstrated anti-cancer activity. This led us to synthesize and explore a new amino-azo-quinoline ligand H2L 1 and its square planar nickel(II) complexes [Ni(HL) (OAc)], 2 and [Ni(HL)Cl], 3 and the structures were determined by Single Crystal X-Ray Diffraction. Theoretical investigation of redox orbitals of the complexes discloses that the reduction process is due to ligand reduction whereas both metal and ligand are contributing towards oxidation. The anti-cancer properties of the ligand and one of the nickel(II) complexes have been assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, cell migration along with the generation of reactive oxygen species using human epithelial cancer cell line cells. The ligand 1 and complex 3 have been found to show effective anti-cancer activity and for the latter, it is more promising. This may be ascribed to the rigid and robust nature of square planar complex 3, which supports stronger binding with DNA than that of free ligands, possibly due to the flexible nature of the latter. This result has also been validated by molecular docking using nine conformers of the ligand and complex 3 via interaction with B-DNA (PDB ID: 1BNA) where the binding affinity with the complex has been found to be stronger.

The off‑target effect of loratadine triggers autophagy‑mediated apoptosis in lung adenocarcinoma cells by deactivating JNK, p38, and STAT3 signaling through both PP2A‑dependent and independent pathways.

Lung adenocarcinoma (LUAD) is a typical inflammation‑associated cancer, and anti‑inflammatory medications can be valuable in cancer therapy. Loratadine, a histamine receptor H1 (HRH1) antagonist, shows both anti‑inflammatory and anticancer properties. The present study aimed to evaluate impacts of loratadine on LUAD cells as well as in a LUAD xenograft mouse model, and explore underlying mechanisms. Mechanistic investigations were conducted through using western blotting, flow cytometry, immunohistochemistry, acridine orange staining, TUNEL assays, and in silico analyses of loratadine‑modulated genes in LUAD specimens. It was observed that loratadine inhibited LUAD cell proliferation and colony formation by inducing autophagy‑mediated apoptotic cell death independently of HRH1. In a LUAD xenograft model, loratadine decreased tumor proliferation and angiogenesis while enhancing autophagy and apoptosis. Mechanistically, loratadine induced protein phosphatase 2A (PP2A) activation to deactivate c‑Jun N‑terminal kinase (JNK)1/2 and p38 in H23 and PC9 LUAD cells. Additionally, loratadine inhibited signal transducer and activator of transcription 3 (STAT3) activation via a PP2A‑independent pathway. Furthermore, the combination of loratadine with inhibitors for JNK, p38 and STAT3 all enhanced proliferation inhibition of loratadine alone in both cell lines. In the clinic, patients with LUAD expressing high PP2A had favorable prognoses. The present study suggests that loratadine can be used as a PP2A activator for LUAD treatment, and the combination of repurposing loratadine with inhibitors of STAT3, JNK and p38 would be an effectively strategy for inhibiting LUAD growth.

Organosulfur Compounds in Garlic for Gastric Cancer Treatment: Anticancer Effects, Overcoming Drug Resistance, and Mechanisms.

Garlic (Allium sativum L.) has been consumed globally as a functional food and traditional medicine for various ailments. Its active organosulfur compounds (OSCs) have demonstrated significant anticancer properties, particularly against gastric cancer. However, a comprehensive review of these effects and the underlying molecular mechanisms, including their role in overcoming drug resistance, is currently lacking. This review systematically examines both preclinical and clinical studies on the anticancer effects of garlic and its organosulfur compounds against gastric cancer, with a focus on patents. Emphasis is placed on explaining the mechanisms of action, exploring how these compounds can overcome drug resistance, and highlighting relevant patents that have been granted in this field. The literature search included databases, like PubMed, Web of Science, Google Scholar, ScienceDirect, and patent databases, including articles and patents published up to October 2024. Preclinical studies demonstrate that garlic-derived organosulfur compounds possess anticancer activities against gastric cancer. They work through multiple mechanisms, including inducing apoptosis, causing cell cycle arrest, inhibiting cancer stem cell properties, suppressing epithelial-mesenchymal transition, and modulating key signaling pathways, like PI3K/Akt and NF-κB. These compounds also show potential in overcoming drug resistance by downregulating multidrug resistance proteins and enhancing the effectiveness of standard chemotherapy drugs. Clinical studies suggest that regular garlic consumption may reduce the risk of gastric cancer and improve outcomes in patients undergoing chemotherapy. This review highlights the significant potential of garlic's organosulfur compounds as complementary agents in gastric cancer prevention and treatment and emphasizes the relevance of existing patents and the need for further clinical trials to confirm these effects and develop effective therapeutic strategies.

Investigating the Antioxidant and Anti-Cancer Properties of Milk Thistle Extract Against the HepG2 Cells

Background: Hepatocellular carcinoma (HCC) is the third among all cancer-related causes of death worldwide. The primary cause of HCC development is oxidative stress. Milk thistle (MT) contains numerous phytochemicals that contain antioxidant and hepatoprotective properties. The goal of this study was to investigate MT's chemical composition and antioxidant activity, as well as its bioactive compound's in vitro anti-cancer efficacy against HepG2 human liver cancer cells.Methods: We analyzed the bioactive components of MT using GC-MS and HPLC methods. The antioxidant activity was measured by the total phenolic, total flavonoid, DPPH, and radical ABTS scavenging. Furthermore, we evaluated the anti-hepatocellular carcinoma activity using the human cell line HepG2. The MTT test was used to calculate the IC50 values of MT. Cell cycle and apoptosis were measured by flow cytometry in the cell lines.Result: Our findings demonstrated that 11 bioactive compounds with antioxidant potential were identified via GC/MS screening. Eighteen bioactive compounds with anti-cancer and antioxidant capabilities were found through HPLC screening. Furthermore, HPLC analysis demonstrated both high quality and number of amino acids. MT stops the growth of HepG2 cells at an IC50 level of 21.727±0.89 μg/ml. Moreover, MT arrested HepG2 cells in the G1 phase and induced apoptosis.Conclusion: The findings of this study indicate that bioactive MT extract has potential therapeutic effects on cancer cells, highlighting the need for further research to explore its mechanisms of action and therapeutic applications in cancer treatment.Keywords: Milk Thistle; Free Radicals; Oxidative Stress; HCC; Anti-oxidants

Carcinogenic and anticancer activities of microbiota-derived secondary bile acids

Secondary bile acids (SBAs), which are metabolites produced by gut microbiota, have been implicated in both carcinogenic and anticancer processes. This review explores the dual role of SBAs, focusing on their molecular mechanisms and biological effects. The carcinogenic activities of SBAs include DNA damage, promotion of oxidative stress, and modulation of signaling pathways that drive tumorigenesis. Conversely, some SBAs exhibit anticancer properties by inducing apoptosis, inhibiting cell proliferation, and modulating immune responses. The article also discusses the complex interplay between SBAs and the host’s genetic and environmental factors, highlighting potential therapeutic implications and the need for targeted strategies to mitigate risks while harnessing beneficial effects. A comprehensive understanding of the delicate equilibrium between the deleterious and salutary impacts of SBAs has the potential to facilitate the development of innovative cancer prevention and treatment methodologies.

Therapeutic Insights of Indole Scaffold‐Based Compounds as Protein Kinase Inhibitors

AbstractCancer is deemed to be one of the most severe diseases, which is accountable for the elevated mortality rate after cardiovascular diseases. Despite the huge numbers of drugs that were approved by the USFDA to combat the prevalence of cancer, the resistance of the diverse cancer types to the current medications as well as their high toxicity becomes an obstacle in cancer therapy. Thus, the developing of new medications with improved selectivity and efficiency to cure various types of cancer disease is still an imperative goal. Kinases are phosphorylating enzymes that catalyze the transfer of phosphate from ATP to tyrosine, serine and threonine residues of proteins, which leads to the activation of varied signaling pathways that regulate various cellular functions such as differentiation, proliferation, migration and angiogenesis. Abnormal phosphorylation leads to various diseases such as cancer, overexpression of kinases was frequently observed in different cancerous tissues. Thus, the suppression of the kinase activity has stood out as a strategic pathway for cancer therapy. Otherwise, indole core has displayed as a privileged scaffold with promising anticancer properties and multi‐kinase suppression effect. This review presents various indole‐based anticancer agents as kinase inhibitors in the recent decade. In addition, the various interactions of indole derivatives within the active pocket of different kinases have been highlighted. This review article comprises research reports from 2014 until the present.

DETERMINATION OF THE ANTIPROLIFERATIVE EFFECT OF STERNBERGIA LUTEA (L.) KER GAWL. EX SPRENG. EXTRACTS ON A375 MALIGNANT MELONOMA CELL LINE

Epidemiological evidence confirms that plants are primary sources of drugs used to reduce the incidence of cancer and prevent cancer-related deaths. Sternbergia species are used for therapeutic purposes due to the amaryllidaceae alkaloids, lectins, phenolic acids, pigments, and volatile components they contain. In this study, the anticancer properties of S. lutea extracts were tested on the A375 malignant melonoma cell line. In addition, in the study, the transcriptional expression of BCL-XL and Cas9 genes, which function in cell proliferation and apoptotic pathways, in cells treated with plant extracts were determined by qRT-PCR. According to the cytotoxicity results made by the MTT test, the highest inhibition percentage was determined at the plant's concentration of 500 μg/𝑚L. At this concentration, A375 cells were inhibited by 83.63%, and the IC50 value of the extract was calculated as 194.64 μg/𝑚L. In addition, in qRT-PCR analyses, a statistically significant increase was observed in the mRNA expression levels of Cas9 genes, which are positively correlated with the apoptotic pathway, in the extract and cisplatin-applied groups compared to the control group.

Chemical Profiling, Antioxidant, and Antiproliferative Activities of Algerian Cistus creticus L. Leaf Extracts: Evidence from In vitro and In Silico Studies.

Research into oxidative stress, cancer, and natural products revealed promising avenues for therapeutic intervention. Natural products are considered potent pharmaceuticals in combating oxidative stress and its relationship with cancer. This study was carried out to evaluate the chemical profile and antioxidant activities using DPPH, ABTS, Phenanthroline, Cupric, Phosphomolybdenum, FRAP, Hydroxyl, Iron chelation in vitro assays, and anticancer properties by MTT method of Cistus creticus extracts. The chemical composition was determined using the LC/MS-MS technique. Therefore, in silico methods, particularly molecular docking and dynamic simulation were applied for molecular interaction analysis. The obtained results revealed a wide variety of phenolic compounds in all studied fractions, in their qualitative and quantitative distribution. In most antioxidant assays, the butanol and ethyl acetate extracts exhibited the most effective effects, followed by the aqueous extract, while the petroleum ether and chloroform fractions exhibited much lower activity in comparison with standards. In parallel, ethyl acetate, n-butanol, and chloroform extracts exhibited potent antiproliferative activity against T47D and A549 cell lines, while the aqueous extract showed an IC50 in the range of mg/ml. Moreover, the analysis of interactions identified compounds against particular targets in studied cell lines using molecular docking showed a great affinity, especially for the ligands Hesperidin, Luteolin-7-O-glucoside and Rutin. Also, the molecular dynamic simulation of the interacting complexes Hesperidin-mTOR, Lutin-EGFR and Apigenin-HER2 revealed precise interaction, providing insights into their stability and dynamic behavior. Furthermore, the studied ligand exhibited interesting pharmacokinetic properties with no reported toxicity. These findings confirmed the potential of Algerian Cistus creticus L. leaf extracts as promising therapeutic molecules for combating oxidative stress and cancer.

Lipidomics-based association study reveals genomic signatures of anti-cancer qualities of pigmented rice sprouts

IntroductionThe genetic wealth present in pigmented rice varieties offer abundant variation in different sources of antioxidants to meet nutritional security targets among rice-consuming communities. There is limited knowledge of the dynamic changes in the lipidome of rice during germination and the corresponding genes associated with the antioxidant and anti-cancerous properties of lipophilic fractions of pigmented rice sprouts (PRS).MethodsIn this study, we profiled the lipidome of diverse pigmented rice collections of germinated sprouts. Further, we employed Genome-wide association studies (GWAS), gene-set analysis, and targeted association analysis to identify the candidate genes linked to these lipids.ResultsThe genetic analyses revealed 72 candidate genes involved in the regulation of these accumulating lipids in PRS. Marker trait associations (MTA) analysis shown that the combination GGTAAC/ACAAGCTGGGCCC was associated with increased levels of unsaturated lipids and carotenoids, which likely underlie these beneficial effects. This superior MTA combination exhibited potent inhibitory activity against HCT116 and A549 cell lines, with average 1/IC50 values of 0.03 and 0.02 (mL/μg), respectively, compared to the inferior MTAs.DiscussionCollectively, our findings demonstrate that MTAs linked to selected GDSL esterase/lipase (GELP) genes, OsACP1, and lecithin-cholesterol acyltransferase significantly enhance antioxidant and anti-cancer properties, potentially through the mobilization of unsaturated lipids and carotenoids during germination. This study offers valuable insights into the health-promoting potential of germinated rice sprouts as a rich dietary source of antioxidants beneficial to human health.

Inhibition of Kinase Activity and In Vitro Downregulation of the Protein Kinases in Lung Cancer and Cervical Cancer Cell Lines and the Identified Known Anticancer Compounds of Ziziphus mucronata

Plants have long been used as sources of natural compounds with therapeutic benefits, providing molecules capable of inhibiting multiple kinases. Many medicinal plants are recognized for their anticancer properties and may offer ways to mitigate the adverse effects of conventional cancer treatments. In this study, the potential of Ziziphus mucronata methanol extract as a kinase inhibitor was assessed using the MTT assay, a universal kinase assay, and a human phosphokinase antibody array, along with a GC-MS analysis of volatile anticancer compounds. The MTT assay revealed strong cytotoxicity in A549 cells, with an IC50 of 31.25 µg/mL, while HeLa cells showed weaker cytotoxicity with an IC50 of 125 µg/mL. In comparison, paclitaxel exhibited potent inhibitory effects on A549 cells (IC50 of 31.25 µg/mL) and moderate inhibition on HeLa cells (IC50 of 65 µg/mL). Enzyme activity, measured by ADP production in the ADP-Glo assay, indicated that the extract inhibited protein kinase activity in both A549 and HeLa cells after 24 h of treatment. Additionally, the human phosphokinase antibody array, which includes 44 pre-spotted kinases, showed that the extract downregulated multiple phosphorylated kinases in both cell lines. Some of the affected kinases, such as TOR, Fyn, HcK, Fgr, STAT5b, PLC-γ1, p38α, ERK1/2, AMPKA, Akt1/2, GSK-3α/β, MSK1/2, CREB, RSK1/2/3, PLC-γ1, and STAT5a are critical regulators of various cellular processes, including apoptosis, differentiation, and proliferation. The findings of this study suggest that extract from Z. mucronata may have the capacity to regulate protein kinase activity, highlighting their significant potential as growth inhibitors for cancer cells.

Lantana camara: A Botanical Treasure with Multidimensional Impacts

Lantana camara, belonging to the Verbenaceae family, is a plant recognized for its extensive distribution and notable medicinal attributes, as well as its unique morphological characteristics and taxonomic complexity. Originally from the Americas, it has become an invasive species in various regions globally. This review delves into the essential features of Lantana camara, emphasizing its morphology, taxonomy, medicinal applications, and industrial relevance. The plant displays a diverse array of morphological traits, such as vibrant inflorescences, ovate foliage, and woody stems, which aid in its identification and ecological adaptability. In terms of taxonomy, Lantana camara is marked by significant variability, with a multitude of cultivars and hybrid varieties presenting challenges to its classification. Lantana camara is recognized in traditional medicine for its wide-ranging therapeutic benefits, which encompass anti-inflammatory, antimicrobial, antidiabetic, and anticancer properties. The plant's medicinal effectiveness is attributed to its bioactive constituents, such as alkaloids, flavonoids, and triterpenoids. In addition to its health-related uses, Lantana camara has attracted interest in several industrial applications, including bioremediation, the extraction of essential oils, and as a potential fiber source for textiles. Although it poses challenges due to its invasive characteristics and ecological consequences, Lantana camara offers significant prospects for sustainable resource utilization in both pharmaceutical and industrial domains. Keywords: Lantana Camara, Pharmacology, Extraction, L. camara leaves, Wild Sage. .

From Structure to Function: Isatin Derivatives as a Promising Class of Antiviral Agents.

A range of heterocyclic compounds, including Isatin (oneH-indole-2, 3-dione) and its by-products, have been shown to represent potential unit blocks in the synthesis of potential medicinal agents. Numerous studies have been carried out on isatin, its synthesis, biological uses, and its chemical composition since when it was discovered. Functionally, these isatin-containing heterocycles have demonstrated antibacterial, antidiabetic, antiviral, antitubercular, and anticancer properties, among many others. In vitro and In vivo efficaciousness of several Isatin moieties has been assessed in recent years based on their antimicrobial qualities. Isatin has shown great promise as a flexible heterocycle in the realm of drug development in recent years. Many viruses have caused extensive epidemics during the last 50 years, which have had detrimental effects on social, economic, and health conditions. The current unprecedented SARS-CoV-2 epidemic necessitates intensive research into the development of potent antiviral medications. It has been shown that Isatin, a flexible heterocycle, has a great deal of potential for drug development. Appropriately functionalized Isatin compounds have shown noteworthy and extensive antiviral activities throughout the last fifty years. The goal of this study is to gather all known data on Isatin derivatives' antiviral activity, emphasizing their structure-activity correlations as well as research on mechanistic and molecular modelling. We think that the scientific community will find this review to be a useful tool in the development of more efficient and powerful antiviral treatments based on Isatin scaffolds.

Anticancer Attributes and Multifaceted Pharmacological Implications of Laetrile and Amygdalin.

Laetrile, known as vitamin B17, is often used interchangeably with amygdalin. Laetrile is a semi-synthesis product of amygdalin, whereas amygdalin is a naturally occurring substance in many plants. Both compounds have a nitrile functional group that, when activated by the intestinal enzyme β-glucosidases, releases hydrogen cyanide. The two compounds have been considered for a long time as alternative therapy for cancer treatment however, findings available in the literature are discordant on the real efficacy of laetrile/amygdalin for the treatment of cancer, often highlighting a negative benefit-risk ratio. In this regard, the study aimed to comprehensively analyze the scientific data on laetrile/amygdalin, with a special emphasis on their pharmacokinetics, underlying pharmacological properties, mode of action as a potent antitumor agent, and effect on human health. The results showed that there is no clear evidence on the efficacy of cancer therapy following laetrile/amygdalin administration, especially at the clinical trial level. However, the in vitro studies of the biological activity of these compounds showed positive effects related to their antifibrotic, anti-inflammatory, antiasthmatic, and immunoregulatory processes. Laetrile's mechanism of action closely resembles amygdalin, affecting cancer signaling pathways. However, due to its cyanide toxicity, it was banned by the food and drug administration (FDA) due to safety concerns. Despite not receiving permission from the FDA, laetrile emerged as an alternative therapy in the 1970s. Nonetheless, continuing research is investigating safer methods of activating Laetrile for targeted cancer treatment. This opens interesting prospects in using these compounds in alternative medical therapies, for which, however, further research is needed.

Preparation of Diosgenin-Functionalized Gold Nanoparticles: From Synthesis to Antitumor Activities

Cancer ranks among the top causes of illness and death globally. Nanotechnology holds considerable promise for enhancing the effectiveness of therapeutic and diagnostic approaches in cancer treatment. Our study presents a promising strategy for applying thiocompound nanomedicine in cancer therapy. Our first study aimed to investigate the biological properties of a new compound thiodiosgenin (TDG)—a new derivative of diosgenin—a natural compound with known antioxidant and anticancer properties. Our current second study aimed to compare the therapeutic efficacy of a new diosgenin—functionalized gold nanoparticles—with its precursor on prostate cancer (DU-145) cell lines. Moreover, the safety of the new thio-derivative and new conjugates was tested against the human epithelial line PNT-2. New advanced analytical techniques were developed for the characterization of nanomaterials using methods such as SP-ICP-MS, UV-Vis, TEM, NMR, FT-IR ELS, and TGA. Our synthetic approach was based, on the one hand, on the ligand exchange of citrates to thiodiosgenin (TDG) on gold nanoparticles, and on the other hand, on the attachment of DG through an ester bond to the linker, which was 3-mercaptopropionic acid (MPA) on gold nanoparticles. Initial in vitro studies indicate that TDG shows greater cytotoxic effects on cancer cells but poses risks to normal prostate epithelial cells (PNT-2). It was demonstrated that all the conjugates produced exhibited significant cytotoxic effects against cancer cells while being less harmful to normal prostate epithelial cells (PNT-2) compared to TDG itself. All the obtained conjugates showed antitumor properties; however, for targeted transport, the system referred to as AuNPs-MPAm1-DG is promising, due to the size of the nanoparticles of 53 nm, zeta potential of -30 mV, and loading content of 27.6%. New methods for synthesizing conjugates with diosgenin were developed and optimized for medical applications. Advanced new analytical methodologies were developed to characterize new conjugates, particularly the use of SP-ICP-MS, to solve existing differences in the shape and morphology of the surface of new conjugates.

Association of Pretreatment Serum Indirect Bilirubin Levels With Prognostic and Therapeutic Value in Patients With Newly Diagnosed Acute Myeloid Leukemia.

Bilirubin has anti-inflammatory, antioxidant, and anti-cancer properties, with an inverse relationship between its levels and cancer risk and prognosis. However, the prognostic value of serum bilirubin in acute myeloid leukemia (AML) remains uncertain. This retrospective study analyzed pretreatment serum total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) in 284 AML patients and 316 healthy controls. The prognostic significance of serum bilirubin levels was determined using the Kaplan-Meier method and Cox proportional hazards model. Pretreatment TBIL and IBIL levels were significantly lower in AML patients compared to controls. TBIL and IBIL levels were significantly higher in the CR/CRh/CRi group than in the non-CR/CRh/CRi group and increased significantly after chemotherapy. Elevated pretreatment TBIL and IBIL were associated with longer overall survival (OS) (p < 0.05) and progression-free survival (PFS) (p < 0.05). Pretreatment IBIL was an independent prognostic factor for OS (hazard ratio [HR], 0.47; 95% confidence interval [CI] 0.28-0.79; p < 0.05) and PFS (HR, 0.53; 95% CI 0.33-0.85; p < 0.05). Elevated pretreatment IBIL levels are correlated with improved OS and PFS, acting as an independent favorable prognostic indicator for AML.

Antiproliferative Effect of Methanolic Extract of Vernonia greggii (Asteraceae) on Human Tumoral HeLa Cells Nanoencapsulated into PLGA-Nanoparticles

Vernonia greggii belongs to the Asteraceae family, and some members of this family have been reported to possess anticancer properties. This study evaluated the antiproliferative effect of V. greggii methanol extract (ME), both in its free form and encapsulated into poly(lactic-co-glycolide) (PLGA) nanoparticles (NPs), on human cervical cancer cells (HeLa) and human epidermal keratinocytes (HaCaT). The extract was subsequently sub-fractionated into n-hexane (F-He), methanol (F-Me), and distilled water (F-Ac) fractions, and their antiproliferative effects were assessed. Time-dependent toxicity on HeLa cells was observed for the free-form fractions, with the F-Me fraction showing the highest efficacy compared to the others. Additionally, an NP formulation based on PLGA and F-Me (NPs F-Me) was developed, achieving 64.21% encapsulation efficiency and 11.38% drug loading. The NPs had an average size of 146.9 nm, a polydispersity index (PDI) of 0.103, and a ζ-potential of 23.3 mV. NPs F-Me were tested on HeLa and HaCaT cells, with toxicity observed at concentrations of 300 and 500 μg/mL, affecting tumor cell morphology. Furthermore, the hemolytic activity of F-Me and NPs F-Me was evaluated. The major bioactive compounds in the F-Me fraction were identified using Liquid Chromatography–Mass Spectrometry (LC-MS). These findings suggest that the F-Me fraction of V. greggii exerts an antineoplastic effect both in its free form and when encapsulated in nanoparticles.

Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth

IntroductionVitamin D3 (cholecalciferol) has demonstrated potential anticancer properties, but its clinical application is limited by associated toxicity at effective doses. This study investigated the use of liposomal encapsulation to increase the therapeutic efficacy of vitamin D3 while mitigating its toxicity.MethodsLiposomal vitamin D3 (VD-LP) was prepared via the film-hydration method and characterized for particle size, polydispersity index, encapsulation efficiency, and long-term stability. In vitro gene expression modulation was evaluated in monocytic THP-1 cells, and antiproliferative effects were assessed in HT29 (colorectal), BT474 (breast), and TRAMP-C1 (prostate) cancer cell lines. In vivo antitumor efficacy and toxicity were tested in a mouse model with subcutaneously implanted MC38 tumors. Tumor growth, survival rates, and serum calcium and phosphate levels were analyzed.ResultsVD-LP demonstrated high encapsulation efficiency and stability over 90 days, with a consistent particle size of approximately 83 nm. VD-LP modulated immune-related and metabolic gene expression in THP-1 cells, including upregulation of antimicrobial peptides and vitamin D receptor genes. VD-LP showed superior antiproliferative effects compared to free vitamin D3 in all tested cancer cell lines. In vivo, VD-LP delayed tumor growth and improved survival without causing hypercalcemia, highlighting its favorable toxicity profile.DiscussionLiposomal encapsulation of vitamin D3 significantly improves its anticancer efficacy while mitigating toxicity, making it a promising strategy for future cancer therapies. VD-LP shows potential for enhanced therapeutic applications with reduced adverse effects, warranting further clinical exploration.

Global transcriptome profiling of ST09 treated breast cancer cells identifies miR-197-5p/GPX3 antioxidant axis as a regulator of tumorigenesis.

ROS (Reactive Oxygen Species) has a dual role in tumorigenesis. Some cancers have high ROS conditions, and others have low ROS. TNBC thrives on high ROS compared to other Breast Cancer subtypes. Several antioxidant enzymes catalyze the detoxification of reactive oxygen species and prevent free radicals from damaging DNA and accumulation of mutation. Curcumin, a polyphenol dietary supplement, acts as a potent antioxidant, is known to reduce inflammation, and has anticancer properties. Here, we aim to understand alterations in the transcriptome (miRNA and mRNA expression) induced by ST09 in breast cancer cell lines. We identified an antioxidant system that is upregulated in breast cancer cell lines. Among the antioxidant enzymes regulated by miRNA was GPX3. A novel miRNA-mRNA antioxidant axis, miR-197-5p/GPX3, was observed in the TNBC cell line. We further validated the regulation of GPX3 by miRNA using luciferase assay. GPX3 overexpression, knockdown, and activity assay indicated the anti-tumorigenic role of GPX3 in the TNBC cell line. Further, treatment of TNBC xenograft with ST09 showed tumor reduction in vivo. ST09 potentiates the effect of standard-of-care (SOC) drug Cisplatin in vivo. ST09 can be exploited as a single chemotherapeutic agent or in combination treatment modalities, reducing the dosage of potent drugs.

Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis

Background: Clear cell renal cell carcinoma (ccRCC) has a high incidence rate and poor prognosis, and currently lacks effective therapies. Recently, peptide-based drugs have shown promise in cancer treatment. In this research, a new endogenous peptide called CBDP1 was discovered in ccRCC and its potential anti-cancer properties were examined. Methods: Peptide expression in ccRCC was analyzed using peptidomics technology to screen for potential antitumor peptides. The effects of the peptide on ccRCC growth and migration were studied through Colony Formation Assay, CCK-8 assay, Transwell Assays, Wound Healing Assay, and animal experiments. Further investigation into the antitumor mechanisms of the peptide was conducted using lentivirus transduction, Western Blot Analysis, qRT-PCR, Immunoprecipitation, Immunofluorescence, and Immunohistochemistry. Results: Our findings reveal that Cathepsin B Derived Peptide 1 (CBDP1) can inhibit the progression of ccRCC both in vitro and in vivo. Through mechanistic investigations, it was revealed that CBDP1 facilitates the interaction between YTHDF2 and the deubiquitinase USP5, thereby impeding the ubiquitination and degradation of YTHDF2. The upregulated YTHDF2 then binds to TRPM3 mRNA and promotes its degradation, ultimately reducing TRPM3 expression levels. These molecular events collectively contribute to the anti-cancer properties of CBDP1. Conclusion: These data indicate that CBDP1 exerts its antitumor effects by regulating the USP5/YTHDF2/TRPM3 axis. CBDP1 emerges as a promising candidate for the treatment of ccRCC.

Lutein and inflammation: a comprehensive review of its mechanisms of action

Lutein, a natural dihydroxy carotenoid and a member of the non-vitamin A carotenoids family, is abundant in yellow-colored fruits and green leafy vegetables such as spinach and lettuce. As the second most common type of carotenoid found in human serum, lutein offers a plethora of medicinal benefits, including anti-cancer, anti-inflammatory, and anti-oxidative properties. It is well-absorbed and systemically localized to the liver, lung, and retina, where it can cross the blood-retina barrier and accumulate in the macular pigment. Due to its anti-oxidative and singlet oxygen quenching properties, lutein is reported to reduce the risk of age-related macular degeneration (AMD). Higher concentrations of fasting plasma carotenoids and enhanced skin yellowing after lutein consumption indicate its presence in various regions of the human body, including the skin, breast, brain, and cervix. Lutein has remarkable benefits for neurodegenerative diseases, cardiovascular health, liver protection, and bone disease prevention. In the central nervous system (CNS), lutein supports brain homeostasis through its antioxidant and anti-inflammatory properties, increasing interleukin-10 (IL-10) and reducing tumor necrosis factor-α (TNF-α). It reduces the risk of coronary artery disease and exerts anti-inflammatory effects on peripheral blood mononuclear cells (PBMCs). Lutein protects against alcohol-induced liver damage by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Additionally, lutein promotes bone health by enhancing mineralized bone nodule development and inhibiting osteoclast production, reducing bone resorption, and suppressing soluble receptor activator of nuclear factor kappa B ligand (RANKL). These multifaceted benefits make lutein a valuable agent in disease prevention and health promotion. This review discusses the comprehensive profile of lutein as a phytochemical activity, including anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, neurological, and cardioprotective effects. Additionally, it discusses lutein’s beneficial impact on macular degeneration and eye diseases, showcasing its potential as a natural, plant-based therapeutic agent.