Cancer HT-29 Cells Research Articles

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.

Design, Synthesis, Anticancer Screening, and Mechanistic Study of Spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide Derivatives.

The present study aims to create spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives with anticancer activities. The in vitro anticancer evaluation showed that only the novel spiro-acenaphthylene tethered-[1,3,4]-thiadiazole (compound 1) exhibited significant anticancer efficacy as a selective inhibitor of tumor-associated isoforms of carbonic anhydrase. Compound 1 demonstrated considerable efficacy against the renal RXF393, colon HT29, and melanoma LOX IMVI cancer cell lines, with IC50 values of 7.01 ± 0.39, 24.3 ± 1.29, and 9.55 ± 0.51 µM, respectively. In comparison, doxorubicin exhibited IC50 values of 13.54 ± 0.82, 13.50 ± 0.71, and 6.08 ± 0.32 µM for the corresponding cell lines. Importantly, compound 1 exhibited lower toxicity to the normal WI 38 cell line than doxorubicin, with IC50 values of 46.20 ± 2.59 and 18.13 ± 0.93 µM, respectively, indicating greater selectivity of the target compound compared to the standard anticancer agent doxorubicin. Also, mechanistic experiments demonstrated that compound 1 exhibits inhibitory activity against human carbonic anhydrase hCA IX and XII, with IC50 values of 0.477 ± 0.03 and 1.933 ± 0.11 μM, respectively, indicating enhanced selectivity for cancer-associated isoforms over cytosolic isoforms hCA I and II, with IC50 values of 7.353 ± 0.36 and 12.560 ± 0.74 μM, respectively. Cell cycle studies revealed that compound 1 caused G1 phase arrest in RXF393 cells, and apoptosis experiments verified a substantial induction of apoptosis with significant levels of early and late apoptosis, as well as necrosis (11.69%, 19.78%, and 3.66%, respectively), comparable to those induced by the conventional cytotoxic agent doxorubicin, at 9.91%, 23.37%, and 6.16%, respectively. Molecular docking experiments confirmed the strong binding affinity of compound 1 to the active sites of hCA IX and XII, highlighting significant interactions with zinc-binding groups and hydrophobic residues. These findings underscore the target compound's potential as a viable anticancer agent via targeting CA.

RuIII-Morpholine-Derived Thiosemicarbazone-Based Metallodrugs: Lysosome-Targeted Anticancer Agents.

The idea of coordinating biologically active ligand systems to metal centers to exploit their synergistic effects has gained momentum. Therefore, in this report, three RuIII complexes 1-3 of morpholine-derived thiosemicarbazone ligands have been prepared and characterized by spectroscopy and HRMS along with the structure of 2 through a single-crystal X-ray diffraction study. The solution stability of 1-3 was tested using conventional techniques such as UV-vis and HRMS. Further, the anticancer activity of 1-3 was tested in HT-29 and HeLa cancer cell lines. To gain insight into their mechanism of action, the cytotoxicity, hydrophobicity, and the interaction of 1-3 with DNA and HSA were evaluated by different conventional methods such as absorption, fluorescence, and circular dichroism studies. Along with favorable biomolecule interaction, 1-3 revealed potent selectivity toward cancer cells, which is a prerequisite for the generation of an anticancer drug. According to cell viability results, 1 has the highest cytotoxicity among all in the group, against both cells, respectively. Additionally, the fluorescence-active ruthenium complexes selectively target lysosomes, which is evaluated by live-cell imaging. 1-3 disrupt the lysosome membrane potential by generating an excessive amount of reactive oxygen species, which results in an apoptotic mode of cell death.

Alginate coated mesoporous silica nanoparticles as oral delivery carrier of curcumin and quercetin to colon cancer: preparation, optimization, characterization, and anticancer activity.

The synergistic bioactive effect of polyphenols can enhance the development of functional foods to prevent chronic diseases such as cancer. Curcumin and quercetin have been shown to possess anticancer properties. The combination of curcumin and quercetin has been shown to provide synergistic effects against cancer cell proliferation. The prospect of exhibiting a synergistic antitumor effect is to target a multi-pathway approach, reduce dosage, and minimize potential side effects. However, their effectiveness is limited by poor bioavailability. Nanoscale delivery systems are promising strategies for the delivery of polyphenols. Nevertheless, many of these nanomaterials are yet to be commercialized owing to their lack of versatility or manufacturing costs. Thus, developing a formulation that responds to body conditions is a great challenge and would provide a better way to orally administer polyphenols. Therefore, this study aimed to develop a dual-responsive disulfide-linked core-shell nanohybrid for oral delivery and targeted release of polyphenols in the colon. The nanohybrid had monodispersed structures with a size of < 50nm, large pore size (> 9.5nm), surface area of > 700 m2/g, and zeta potential of - 30.71 ± 0.71mV. The polyphenols were encapsulated into the nanohybrid in their amorphous state, with a loading capacity of20.49%.The coatingenhancedthe release of polyphenols into the intestinal fluid, potentially improving their delivery to the colon. The nanohybrid demonstrated a better anticancer effect than the free polyphenolsagainst HT29 cancer cells. This study explores the use of adual-sensitive alginate-coated mesoporous silica nanohybridas a carrier for the enhanced delivery of polyphenols.

Antitumor activity of edible fishes (Channa striata and Anabas testudineus) and gastropods (Helix aspersa and Pila virens) rudimentary mucus against HT-29 cell line and its biochemical properties

BackgroundThe mucus from fish and gastropods contains a wide range of bioactive molecules with biomedical properties. The fish and gastropods were collected from Oragadam lake, Kanchipuram district, Tamil Nadu, India. In this study, we wanted to examine the anticancer potential of fish and gastropods mucus. The biochemical components of the crude mucus were screened.ResultsThe biochemical analysis showed that the mucus of Anabas testudineus and Pila virens contained a high level of carbohydrates (2.8 and 1.5 mg/ml), the mucus of Channa striata contained a high level of lipids (0.9 mg/ml), and the mucus of Helix aspersa contained a high level of protein (1.3 mg/ml). The results showed morphological variations in the HT-29 cells upon treatment with crude mucus. Upon 24 h of gestation, the frozen cells began to shrink and seem round in shape. Using the MTT assay, the mucus crude extract was evaluated for its anticancer properties against the human colon cancer cell line (HT 29). The inhibitory concentration (IC50) was determined at 100 µg/ml after 24 h. Using specific staining techniques; fluorescent microscopy was utilized to examine the cell morphology and early and late apoptotic stages. Propidium iodide staining showed nuclear damage followed by DNA damage. This showed that the rudimentary mucus could prompt cell death and increased the number of fragments and mucus concentration, respectively.ConclusionThis study showed that the edible or commercially important fish and gastropod mucus have potential anticancer activity against HT-29 cancer cells.

Targeting the Hippo and Rap1 signaling pathways: the anti-proliferative effects of curcumin in colorectal cancer cell lines.

CRC has the third-highest cancer incidence and death. Many human cancers, including colorectal cancer, are connected to abnormal signaling pathway gene expression. Many human malignancies include Hippo and Rap1 signaling. This research examined curcumin's therapeutic effects on colorectal cancer cell lines' Hippo and Rap1 signaling pathway genes. The role of the above signaling pathways is considered in colorectal cancer development. No research has examined curcumin's influence on key genes in these pathways; thus, this work ismeant to uncover its more precise mechanism. First, the gene expression omnibus database is queried to discover GSE8671, a dataset that contains differentially expressed genes associated in CRC formation. DAVID was used to discover the corporation of these genes and signaling pathways (Hippo and Rap1), and the cancer genome atlas (TCGA) database was utilized to select genes and assess their expression and biomarker potential. MTT, apoptosis, and quantitative PCR were used to assess whether curcumin is therapeutic for colorectal cancer cell lines. An in-silico analysis identified the dysregulation of several critical genes AXIN2, MYC, TEAD4, MET, LPAR1, and ADCY9 in colorectal cancer, highlighting their involvement in the Hippo and Rap1 signaling pathways. Experimental assessments, including MTT assays, apoptosis assays, and quantitative PCR (qPCR) analysis, demonstrated that the targeted modulation of these genes effectively inhibits cancer cell proliferation. Specifically, treatment with curcumin resulted in a significant reduction in cell viability in HT-29 and HCT-116 colorectal cancer cell lines, thereby facilitating apoptotic cell death. Furthermore, curcumin administration was associated with the upregulation of LPAR1 and ADCY9 gene expression, while concurrently downregulating AXIN2, MYC, TEAD4, and MET in both cell lines. This study reveals compelling evidence of curcumin's potent anticancer properties, highlighting its transformative influence on the Hippo and Rap1 signaling pathways within colorectal cancer cells. These findings not only underscore curcumin's potential as a therapeutic agent but also pave the way for innovative strategies in the fight against colorectal cancer.

Selected Metal (Au, Ag, and Cu) Complexes of N-heterocyclic Ligands as Potential Anticancer Agents: A Review.

Nitrogen-based organic heterocyclic compounds are an important source of therapeutic agents. About 75% of drugs approved by the FDA and currently available in the market are N-heterocyclic organic compounds. The N-heterocyclic organic compounds like pyridine, indole, triazoles, triazine, imidazoles, benzimidazoles, quinazolines, pyrazoles, quinolines, pyrimidines, porphyrin, etc. have demonstrated significant biological activities. These heterocyclic organic compounds also coordinate with various metal ions and form coordination compounds. Most of them have shown improved biological activities. The research on the metal complexes of these compounds reported their significant biological activities. N-heterocyclic-based metal complexes showed outstanding anticancer activities against different cancer cell lines, including VEGFR-2, HT-29, MDA-MB-231, MCF-7 K562, A549, HepG2, HL60, A2780, WI-38, Colo-205, PC-3, and other cancer cell lines. Some of these compounds showed better anticancer activity than cisplatin. In this review, we summarized the anticancer properties of N-heterocyclic-based gold (Au), silver (Ag), and copper (Cu) complexes and explored the mechanisms of action and potential structure-activity relationships (SAR) of these complexes. Our goal is to assist researchers in designing highly potent N-heterocyclic-based Au, Ag, and Cu complexes for the potential treatment of various cancers.

Nano-Exopolysaccharide from Probiotic Lactobacillus brevis Impact against Cancer Cells Caco and HT-29 Development based on ROS, IL-6, IL-8, TNF-β and M30

Nano-Exopolysaccharide from Probiotic Lactobacillus brevis Impact against Cancer Cells Caco and HT-29 Development based on ROS, IL-6, IL-8, TNF-β and M30

Evaluation of Anticancer and Antimicrobial Potentials of Tarantula cubensis Venom (Theranekron® D6)

Tarantula cubensis venom (Theranekron®D6) is widely used in veterinary medicine as a drug with anti-tumor, wound healing, anti-inflammatory, antiphlogistic properties. The purpose of the study was to explore Theranekron®D6 (TD6)'s antibacterial activity and its impact on apoptotic cell death in human colon and liver cancer cell lines. TD6 showed a dose and time dependent cytotoxic effect at 12h and 24h in HT-29 and HUH-7 cancer cell lines. The IC50 values of TD6 were calculated as 12.18 µg/mL and 25.10 µg/mL in HT-29 and HUH-7 cell lines at 24h, respectively. TD6 induced apoptosis in HT-29 and HUH-7 cell lines. In these cells exposed to TD6, while the BAX/BCL-2 ratio and CASP-3 mRNA level increased, the HSP90 mRNA and protein level decreased. Also, TD6 exhibited antimicrobial activities against Pseudomonas aeruginosa, Enterococcus faecalis, Klebsiella pneumonia, Staphylococcus aureus, Candida albicans and Candida utilis. Obtained results demonstrated that TD6 has great potentials as alternative therapeutic for cancer and infectious diseases as apoptosis inducer and antimicrobial agent.

In Vitro and In Silico Evaluation of Syzygium aromaticum Essential Oil: Effects on Mitochondrial Function and Cytotoxic Potential Against Cancer Cells.

The current study proposes the in vitro and in silico anticancer evaluation of clove (Syzygium aromaticum L.) essential oil (CEO). The steam hydrodistillation method used yielded 10.7% (wt) CEO. GC-MS analysis revealed that the obtained oil is rich in eugenol (75%), β-caryophyllene (20%), and α- caryophyllene (2.8%) and also contains several other minor components accounting for approximately 1.5%. The DPPH-based scavenging antioxidant activity was assessed for the obtained CEO, exhibiting an IC50 value of 158 μg/mL. The cytotoxic effects of CEO, its major component eugenol, and CEO solubilized with Tween-20 and PEG-400 were tested against both noncancerous HaCaT cells and HT-29 human colorectal adenocarcinoma, RPMI-7951 melanoma, A431 skin carcinoma, and NCI-H460 non-small lung cancer cells, using the Alamar Blue and LDH assay after 48 h treatment. The Tween-20 and PEG-400 CEO formulations, at 200 μg/mL, recorded the highest cytotoxic and selective effects against RPMI-7951 (72.75% and 71.56%), HT-29 (71.51% and 45.43%), and A431 cells (61.62% and 59.65%). Furthermore, CEO disrupted mitochondrial function and uncoupled oxidative phosphorylation. This effect was more potent for the CEO against the RPMI-7951 and HT-29 cells, whereas for the other two tested cell lines, a more potent inhibition of mitochondrial function was attributed to eugenol. The present study is the first to specifically investigate the effects of CEO and Tween-20 and PEG-400 CEO formulations on the mitochondrial function of RPMI-7951, HT-29, A431, and NCI-H460 cancer cell lines using high-resolution respirometry, providing novel insights into their impact on mitochondrial respiration and bioenergetics in cancer cells. The results obtained may explain the increased ROS production observed in cancer cell lines treated with eugenol and CEO. Molecular docking identified potential protein targets, related to the CEO anticancer activity, in the form of PI3Kα, where the highest active theoretical inhibitor was calamenene (-7.5 kcal/mol). Docking results also showed that calamenene was the overall most active theoretical inhibitor for all docked proteins and indicated a potential presence of synergistic effects among all CEO constituents.

Raspberry Pomace as a Good Additive to Apple Freeze-Dried Fruit Bars: Biological Properties and Sensory Evaluation.

This study investigated the impact of adding raspberry pomace to the phenolic content and biological properties of freeze-dried apple/raspberry bars. The bars were prepared by replacing apple puree with raspberry pomace (5-50%), and their phenolic compounds were assessed using ethanol and buffer extracts. This work also explored the potential bioaccessibility of phenolic compounds in enriched bars through a simulated digestion process (digest). Antioxidant, anti-inflammatory (LOX, COX-2 inhibition), antihypertensive (ACE inhibition), and antiproliferative effects on AGS and HT-29 cancer cells were evaluated. The total polyphenol content was highest in the all bar variants post-digestion. The highest-904.26 ± 23.5 mg/100 g-was determined for the B50 sample In the enriched bars, the concentration of chlorogenic acid decreased from 6.99 ± 1.08 mg/L for BP5 to 2.75 ± 0.32 mg/L for BP50, but the ellagic acid concentration increased from 1.46 ± 0.02 mg/L for BP5 to 12.73 ± 0.09 mg/L for BP50. Among the tested extracts, the highest antioxidant and LOX, COX-2 inhibiting activity was determined for digest. The ability to neutralize free radicals increased with raspberry pomace addition from 3.63 ± 0.26 mM TE/100 g for BC to 5.58 ± 0.22 mM TE/100 g for the BP50 sample. ACE inhibition was quite similar for ethanolic and digest extracts, but much weaker for buffer extracts. The lowest EC50 value was 1.04 ± 0.03 mg/mL for the BP30 ethanolic sample. Analyzed extracts showed antiproliferative activity against both tested cell lines. The EC50 values for HT-29 cancer cells decreased from 0.354 ± 0.031 mg/mL for BC to 0.026 ± 0.006 mg/mL for the BP50 digest sample. It can be assumed that the BP30 bar best met the assumed criteria, and is optimal for both sensory quality (receiving an average score of 4.45) and health benefits.

Furan- and Furopyrimidine-Based Derivatives: Synthesis, VEGFR-2 Inhibition, and In Vitro Cytotoxicity.

New derivatives 4a-d, 6, 7a-d, 8a-c, 9, 11a, 11b, 12a-f, 13a-c, and 14 were synthesized and evaluated for their VEGFR-2 inhibition. Compounds 4c, 7b, and 7c showed remarkable enzyme inhibition (IC50 = 57.1, 42.5, and 52.5 nM, respectively) relative to sorafenib (IC50 = 41.1 nM) and were assessed for their cytotoxicity versus HepG2, MCF-7, A549, HT-29, and PC3 cancer cell lines in addition to WI-38. Compound 7b displayed nearly equipotent cytotoxicity against A549 and HT-29 (IC50 = 6.66 and 8.51 μM) compared to sorafenib (IC50 = 6.60 and 8.78 μM). Cell cycle analysis and apoptotic assay of 7b in the HT-29 cell line showed cellular growth arrest at the G2/M phase in addition to the induction of apoptosis. Western blot analysis of compound 7b revealed the deactivation of VEGFR-2. Moreover, a wound healing assay of 7b showed inhibition of wound closure. Additionally, molecular modeling studies of compounds 4c, 7b, and 7c were carried out.

Combining in silico and in vitro approaches for understanding the mechanism of action of the galactomannan extracted from Cassia grandis seeds against colorectal cancer

This study aimed to investigate the antitumor activity of galactomannan extracted from Cassia grandis seeds (GCg) against colorectal cancer cells using both experimental and computational approaches. Galactomannan was extracted from C. grandis seeds and prepared into solutions with varying concentrations. The cytotoxicity of these solutions was tested on HT-29 and HCT-116 colorectal cancer cell lines using the MTT assay. Additionally, computational evaluations, including molecular docking and molecular dynamics simulations, were performed to explore the potential binding interactions of GCg with cyclin-dependent kinase 2 (CDK2). The experimental results demonstrated that GCg significantly inhibited the proliferation of HT-29 cells, especially at concentrations of 5 mg/mL. On the other hand, no concentration inhibited >30 % of HCT-116 cells. Computational analysis revealed that GCg could bind to the ATP-binding site of CDK2, promoting the inactive DFG-out conformation, similar to the known inhibitor K03861. This interaction suggests a mechanism through which GCg may exert its anticancer effects. GCg exhibits significant cytotoxic activity against HT-29 colorectal adenocarcinoma cells, likely through the inhibition of CDK2; however, its efficacy against HCT-116 cells is limited, possibly due to structural differences in the molecular targets. To the best of the authors' knowledge, no studies have explored the applications of GCg in cancers, particularly colorectal ones. Further studies are needed to explore the antimetastatic effects and potential clinical applications of GCg in colorectal cancer treatment.

A new furanoditerpene from Saururus chinensis aerial parts

A new furanoditerpene, saurufuranol (1) along with a flavonoid, 3,5,7,3′,4′-pentamethoxyflavone (2), and eight lignans including macelignan (3), 5-((2R,3R)-4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl)benzo[d][1,3]dioxole (4), dihydroguaiaretic acid (5), (+)-zuonin A (6), sauchinone (7), saucerneol A (8), manassantin A (9) and saucerneol C (10). Their structures were determined by extensive spectroscopic studies using NMR spectroscopy and mass spectrometry in combination with literature. These compounds were evaluated cytotoxicity on PC-9 and HT-29 cancer cell line. Compound 8 showed significant activity on both of cancer cell lines with IC50 values of 1.33±0.23 and 1.18±0.27 µM, respectively.

ONC206, an imipridone derivative, demonstrates anti-colorectal cancer activity against stem/progenitor cells in 3D cell cultures and in patient-derived organoids.

Colorectal cancer (CRC) remains one of the most frequently diagnosed and life-threatening malignancies worldwide. CRC's high recurrence rates and drug resistance have been correlated with a subpopulation of dormant slowly dividing cells termed CRC stem cells (CCSCs). Consequently, there is a pressing need to identify novel therapeutics that can effectively and specifically target CCSCs. Imipridones are promising structurally related anticancer molecules that showed efficacy in several solid and hematological preclinical models and phase I/II/III clinical trials. This study mainly aimed to assess the potential anticancer effects of ONC206, an imipridone derivative, on CRC three-dimensional in vitro culture systems using HCT116 and HT29 cells. Importantly, the study aimed at using CRC patient-derived organoids (PDOs) to test the potential therapeutic effect of ONC206. Two-dimensional cell proliferation, viability, migration, and invasion assays were used to assess the effects of ONC206 on two colorectal cancer cell lines, HCT116 and HT29, in vitro. Immunofluorescence imaging, flow cytometry, and western blot analysis were also performed to investigate the mechanism of action of this drug. Sphere formation assay and CRC PDOs were employed to evaluate the effect of ONC206 on CRC cells in a 3D setting and specifically its potency in targeting the CRC stem/progenitor subpopulation of cells. Our results showed that ONC206 was more potent than its parental moleculeONC201 in inhibiting the proliferation and viability of HCT116 and HT29 cells. Moreover, ONC206 significantly reduced the migration and invasion indices of CRC cells. These effects were accompanied by an increase in reactive oxygen species (ROS) production, sub-G1 phase accumulation, and apoptosis in HCT116 and HT29 cells. Furthermore, ONC206 significantly inhibited the 3D colonospheres growth and self-renewal ability of CCSCs more potently than ONC201, which was associated with a decrease in the expression of CSC-related markers. Lastly, ONC206 significantly reduced the growth of organoids derived from CRC patients. Collectively, our findings demonstrate that ONC206 is an effective anticancer molecule capable of targeting CCSCs, which may represent a novel therapeutic strategy that can overcome CRC resistance and recurrence.

Evaluation of safety and biomedical potential of water-soluble oat lignin Avena sativa L.

The study of the value of lignin for biomedical use is generating growing interest. For the first time, the safety and biological efficacy of lignin from the stems of the oat Avena sativa L. were studied, necessary for a preliminary assessment of its biomedical potential, have been studied. In vitro experiments, a sample of oat lignin exhibited cytotoxicity to the HeLa, A549, and HT-29 cancer cell lines, depending on the concentration. At maximum concentrations 125 and 150 μg/ml, it reduced their survival and increased the level of reactive oxygen species. In vivo experiments, a sample of oat lignin, with acute (from 5 to 250 mg/kg body weight) and chronic (300, 1200 and 2000 mg/kg body weight) administration, did not have a toxic or genotoxic effect on the organs of mice. The biological efficacy of the oat lignin was manifested in activation of repair processes in bone marrow and thyroid gland, a decrease in the level of abnormal spermatozoa in males, stimulation of reproductive performance of females and in increase in research activity and a decrease in the level of anxiety in animals. The results indicate the prospects for further study of the medical and biological potential lignin of the oat.

5-Fluorouracil/curcumin loaded silk fibroin hydrogel for the adjuvant therapy in colorectal cancer

This study employed silk fibroin (SF) as a carrier material to encapsulate curcumin (CUR) and 5-fluorouracil (5-FU), forming a highly effective drug-loaded hydrogel. The process involved mixing SF solution containing 5-FU with curcumin solution dissolved in acetone (AC), leading to the formation of composite drug-loaded nanospheres with particle sizes ranging from 77.87 nm to 299.22 nm, demonstrated enhanced permeability and retention (EPR) effects, enabling passive targeting of solid tumors. After the formation of the nanospheres, they were dispersed into a solution containing SF and polyethylene glycol (PEG). Following gelation and PEG removal, a SF hydrogel loaded with 5-FU and CUR (5-FU/CUR@SF hydrogel) was obtained. Results indicated that the 5-FU/CUR@SF hydrogel exhibited excellent drug release properties, with 5-FU and CUR achieving sustained release of 59.66 ± 3.76 % and 47.94 ± 5.03 %, respectively, over a 400-h of sustainable releasing period. Human colorectal cancer cell line (HT-29) and normal human colon epithelial cell line (NCM-460) were cultured with the 5-FU/CUR@SF hydrogel, resulting an apoptosis rate of only 17.38 ± 1.98 % for NCM-460 cells, whereas the apoptosis rate for HT-29 cells significantly increased to 72.31 ± 2.18 %, and its cell viability dropped to 59.77 ± 0.55 %. These findings suggest that the 5-FU/CUR@SF hydrogel exhibits low cytotoxicity toward normal NCM-460 cells, while exerting significant and sustained inhibitory effects on HT-29 cancer cells. In conclusion, the SF-based drug-loaded composite hydrogel holds great potential as a novel adjuvant therapeutic strategy for the treatment of CRC.

Design, in silico studies and biological evaluation of novel chalcones tethered triazolo[3,4-a]isoquinoline as EGFR inhibitors targeting resistance in non-small cell lung cancer

A novel series of six [1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-ones (3a–3f) was designed and synthesized. They were characterized based on spectral and elemental analyses. In silico studies were also committed to provide insights and a better understanding of their structural features. The six compounds were screened for their antiproliferative activity using the MTT assay against five human cancer cell lines, namely, A549, HCT116, PC3, HT29, and MCF-7 in parallel with the non-cancerous human lung cell line WI-38. The results showed that 3e and 3f have potential cytotoxic activities, especially on A549 cells with IC50 = 2.3 µM and 1.15 µM, respectively. Meanwhile, they recorded a minimal cytotoxic effect on WI-38 cells. Concerning the molecular mechanism of action, the present study showed the inhibitory effect of the six compounds against total EGFR. The most potent EGFR inhibitors were 3e and 3f with IC50 = 0.031 µM and 0.023 µM, respectively. The selectivity index of 3f for EGFRT790M was 1.81 times more selective than that of lapatinib. In addition, 3e and 3f initiated cell cycle arrest at the G2/M and pre-G1 phases along with the downregulation of anti-apoptotic protein Bcl2 and the upregulation of pro-apoptotic proteins: p53, Bax, and caspases 3, 8, and 9. Further studies are recommended to evaluate animal models’ promising anticancer activity and molecular mechanism of triazolo[3,4-a]isoquinoline derivatives 3e and 3f.

Synergistic Inhibition of Colorectal Cancer Cells by Autocrine Motility Factor Peptide and Glycyrrhetinic Acid.

Anti-cancer peptides are a powerful drug concept that induces cancer cell death through growth inhibition and membrane disruption, providing broad efficacy. The autocrine motility factor (AMF) interacts with the AMF receptor, regulating cancer cell motility, proliferation, metastasis, and angiogenesis through autocrine and paracrine pathways. However, studies verifying the synergistic effect of the combined use of anti-cancer drugs extracted from plants and AMF treatment are insufficient. The effects of AMF-derived peptide sequences were evaluated in HT29 and SW620 colorectal cancer (CRC) cell lines. The study assessed the impact of AMF peptides on cell proliferation, colony formation, the Nicotinamide Adenine Dinucleotide Phosphate/Reduced Nicotinamide Adenine Dinucleotide Phosphate (NADP+/NADPH) ratio, and reactive oxygen species (ROS) generation in these CRC cells. Additionally, the combined effect of AMF peptides and glycyrrhetinic acid (GA), a compound derived from licorice plants, was investigated by analyzing cell proliferation, colony formation, ROS production, and cell cycle progression in CRC cells. AMF peptides significantly inhibited CRC cell growth (p < 0.05), decreased colony formation (p < 0.05), and increased the NADP+/NADPH ratio (p < 0.05) and ROS production (p < 0.001). When combined with GA, AMF peptides enhanced GA's effects on CRC cells, further suppressing cell growth (p < 0.05) and colony formation (p < 0.05) while increasing ROS generation (p < 0.05). The synergy between AMF peptides and GA, derived from licorice plants, suggests the potential for combined peptide-phytochemical therapy for treating CRC.

Advancements in Quinazoline Derivatives as Targeted Anticancer Agents: A Review on its Synthesis, Mechanisms, and Therapeutic Potential

This review focuses on the advancements in the design, synthesis, and evaluation of quinazoline derivatives as potential anticancer agents. Quinazoline, a versatile nitrogen-containing heterocyclic compound, has gained significant attention due to its biological activities and its ability to target key kinases involved in cancer progression, such as EGFR, VEGFR-2, JAK2, MPS1, and PLK1. Since 2000, numerous quinazoline-based derivatives have been synthesized, demonstrating varying degrees of anticancer potency against a range of cancer cell lines, including MCF-7, A549, HT-29, and HepG2. These derivatives, modified with functional groups such as aniline, aryloxy, pyrazole, thiazole, and hydroxamic acid, have shown promise as potential alternatives to conventional chemotherapeutic agents. Notably, compounds such as 51, 52, 53, and 62 have exhibited potent anticancer activity with IC50 values ranging from sub-micromolar to micromolar concentrations. The review highlights the significant therapeutic potential of quinazoline derivatives, particularly in targeting tyrosine kinases involved in cell proliferation, survival, and metastasis. Furthermore, the synthesis and structure-activity relationships (SAR) of these compounds are discussed, offering valuable insights for the development of new quinazoline analogues as targeted cancer therapies. Although promising, further studies are needed to refine their clinical efficacy and explore their full potential in diverse cancer models.