Human Colon Carcinoma Cells Research Articles

The genetic interaction map of the human solute carrier superfamily.

Solute carriers (SLCs), the largest superfamily of transporter proteins in humans with about 450 members, control the movement of molecules across membranes. A typical human cell expresses over 200 different SLCs, yet their collective influence on cell phenotypes is not well understood due to overlapping substrate specificities and expression patterns. To address this, we performed systematic pairwise gene double knockouts using CRISPR-Cas12a and -Cas9 in human colon carcinoma cells. A total of 1,088,605 guide combinations were used to interrogate 35,421 SLC-SLC and SLC-enzyme double knockout combinations across multiple growth conditions, uncovering 1236 genetic interactions with a growth phenotype. Further exploration of an interaction between the mitochondrial citrate/malate exchanger SLC25A1 and the zinc transporter SLC39A1 revealed an unexpected role for SLC39A1 in metabolic reprogramming and anti-apoptotic signaling. This full-scale genetic interaction map of human SLC transporters is the backbone for understanding the intricate functional network of SLCs in cellular systems and generates hypotheses for pharmacological target exploitation in cancer and other diseases. The results are available at https://re-solute.eu/resources/dashboards/genomics/ .

Demethylated miR-184 regulates EPB41L5 and downregulates Notch signaling to inhibit metastasis in colorectal cancer.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with metastasis being a major contributor to poor prognosis. MicroRNA-184 (miR-184) has been implicated in the progression of various cancers, but its role in CRC metastasis remains poorly defined. This study investigated the effects of miR-184 promoter demethylation on EPB41L5 expression and Notch signaling in CRC. SW620 human colon carcinoma cells were treated with the DNA methylation inhibitor 5-Aza for 96h. Methylation status was assessed via bisulfite sequencing, and gene expression was evaluated using qRT-PCR and Western blotting. Functional assays were conducted to assess cell proliferation, apoptosis, migration, and invasion. 5-Aza treatment significantly decreased miR-184 promoter methylation, leading to increased miR-184 expression. This upregulation suppressed CRC cell migration and invasion, induced G2/M cell cycle arrest, and promoted apoptosis. Mechanistically, miR-184 inhibited EPB41L5 expression, thereby downregulating the Notch signaling pathway and modulating epithelial-mesenchymal transition markers. High EPB41L5 expression in CRC tissues was associated with worse prognosis. These findings suggest that demethylated miR-184 inhibits CRC metastasis by targeting the EPB41L5/Notch signaling axis. This regulatory pathway may serve as a novel prognostic biomarker and therapeutic target, with potential clinical implications for the prevention and treatment of metastatic colorectal cancer.

Enhancing the Nutritional and Health-Related Properties of Taralli Through the Use of Pleurotus eryngii: Focus on Antioxidant and Anti-Inflammatory Properties.

In this study, a portion of whole durum wheat semolina was replaced with Pleurotus eryngii powder (PeP) at concentrations of 5% and 10% (w/w) to produce two taralli variants, TPE5 and TPE10. The impact of PeP on the technological, chemical, physical, and sensory properties of taralli was evaluated. The functional characteristics of the enriched taralli were assessed employing HCT8 human colon carcinoma cells as the experimental model. The inclusion of PeP in taralli increased total dietary fiber, meeting the "high fiber" criteria under Regulation 1924/2006 while also enhancing the total phenol content. The higher fiber and polyphenol content in the enriched samples contributed to a significant reduction in glycemic index and starch hydrolysis. Treatment with PeP-enriched taralli resulted in a notable decrease in intracellular ROS levels in HCT8 cells, demonstrating strong antioxidant potential. Furthermore, TPE5 exerted beneficial effects by reducing inflammation-evidenced by a significant decrease in NFkB phosphorylation at serine 536-and by promoting apoptosis. These effects are likely mediated through the regulation of intracellular oxidative states. Overall, these findings indicate that PeP enrichment enhances the nutritional profile of taralli and provides potential health benefits, reinforcing its role as a valuable functional ingredient.

Isolation and Characterization of L-Asparaginase-Producing Bacteria from the Arabian-Persian Gulf Region: First Report on Bacillus xiamenensis ASP-J1-4 as a Producer and Its Potential Application.

L-asparaginase (L-ASNase) functions as a chemotherapeutic enzyme with antitumor properties. It facilitates the degradation of L-asparagine (L-ASN), a vital amino acid required for the proliferation of tumor cells. In this study, we have isolated 177 L-ASNase-producing strains from the aquatic environment of the Arabian-Persian Gulf. The most potent isolate, ASP-J1-4, was an endophyte recovered from the seablite Suaeda maritima and was molecularly identified as B. xiamenensis (accession number PQ593941). The enzyme purified through DEAE-Sepharose displayed a molecular weight of 37 kDa based on the SDS-PAGE profile and lacked detectable L-glutaminase (L-GTNase) activity. Optimal enzyme activity was at 40 °C and pH 9.0, with stability at pH 7-9. The maximum stimulation effect was found in the presence of Fe3+, Mn2+, and Na+ ions, respectively. The enzyme demonstrated a Vmax of 35.71 U/mL and a Km of 0.15 mM. Interestingly, ASP-J1-4 L-ASNase showed a dose-dependent inhibition against human colon carcinoma (HCT-116) and cervical Henrietta Lacks (HeLa) cell lines, with IC50 values of 15.42 µg/mL and 12.13 µg/mL, respectively. These findings collectively suggest a biocompatible, efficient, and robust enzyme for potential applications in tumor therapy after validation of in vivo studies and clinical trials. This study introduces the first deep screening program for L-ASNase-producing bacteria harboring in the Arabian-Persian Gulf region. In addition, it launches B. xiamenensis and other species as new sources of L-ASNase.

Antiviral Effect of Erdosteine in Cells Infected with Human Respiratory Viruses.

Respiratory viral infections trigger immune and inflammatory responses that can be associated with excessive oxidative stress, glutathione (GSH) depletion, and a cytokine storm that drives virus-induced cell/tissue damage and severe disease. Erdosteine is a thiol-based drug with proven mucolytic, anti-inflammatory, antioxidant, and antibacterial properties, but less is known about its antiviral effects. We performed in vitro studies to investigate the antiviral and anti-inflammatory activity of erdosteine in A549-hACE2 human lung epithelial cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory syncytial virus (RSV) and in Caco-2 human colon carcinoma cells infected with influenza A virus (H1N1). The cells were treated with different concentrations of erdosteine or its active metabolite 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MET-1) before and after viral infection. The viral replication/load in the cell culture supernatants was measured by real-time quantitative polymerase chain reaction (RT-qPCR) assay and digital droplet PCR. The gene expression of innate immune response signaling pathways and oxidative stress was analyzed by reverse transcription PCR custom-array. The results showed that erdosteine and its active metabolite, at concentrations consistent with an approved therapeutic human dosage, were not directly cytotoxic and had significant antiviral effects in cells pre-infected with SARS-CoV-2, RSV, and H1N1. The transcriptome analysis showed that erdosteine activated innate immune responses by stimulating overexpression of type I interferon and inflammasome pathways and modulated oxidative stress by inducing the modulation of oxidative stress and GSH pathways. These findings suggest that erdosteine may be a useful treatment for respiratory viral infections.

Evaluation of Bioactivity of Essential Oils: Cytotoxic/Genotoxic Effects on Colorectal Cancer Cell Lines, Antibacterial Activity, and Survival of Lactic Acid Bacteria.

Colorectal cancer (CRC) ranks among the most frequently diagnosed malignancies and is associated with a significantly high mortality rate. In recent years, increasing attention has been directed toward naturally derived substances with anticancer properties. In our study, we focused on determining the biological and antibacterial effects of selected essential oils (EOs)-peppermint, oregano, tea tree, lemon, lavender, frankincense, and oil blends (Zengest and OnGuard). Analyses were performed on human colon carcinoma cell lines (HCT-116 and HT-29). The cytotoxic (MTT assay), genotoxic effects (comet assay), and reactive oxygen species levels (ROS-Glo™ H2O2 Assay) of EOs and oil blends were determined. In our study, we found that all of the studied oils have the potential cyto/genotoxic effects on CRC cell lines after 24 h exposure. The results revealed that oregano, Zengest, and frankincense showed statistically the highest cytotoxic effects [IC50 0.05 µg/mL] compared to the other studied oils. These oils induced DNA damage and also increased ROS levels. On the other hand, peppermint was shown to have the lowest cytotoxic effect [IC50 0.67 µg/mL] on the HT-29 cell line. We also evaluated the antibacterial effects of oregano, tea tree, and the OnGuard blend, determining their impact on the viability of beneficial bacteria models, including Lacticaseibacillus rhamnosus, Lactiplantibacillus plantarum, Lacticaseibacillus paracasei, Lactobacillus brevis, Lactobacillus pentosus, and Weizmannia coagulans. Oregano exhibited strong antibacterial activity, with an inhibition zone of 31 mm, while tea tree and OnGuard showed inhibition zones ranging from 12 to 15 mm. The EOs (oregano, tea tree, OnGuard) demonstrated antibacterial effects, with MICs ranging from 0.05 to 0.5 µg/mL. Peppermint, lemon, lavender, frankincense, and the Zengest blend did not inhibit the growth of lactic acid bacteria or W. coagulans, and thus did not impact bacterial survival. On the other hand, they demonstrated potential anticancer effects.

Transcription Factor Inhibition as a Potential Additional Mechanism of Action of Pyrrolobenzodiazepine (PBD) Dimers

Background: The pyrrolobenzodiazepine (PBD) dimer SJG-136 reached Phase II clinical trials in ovarian cancer and leukaemia in the UK and USA in the 2000s. Several structural analogues of SJG-136 are currently in clinical development as payloads for Antibody-Drug Conjugates (ADCs). There is growing evidence that PBDs exert their pharmacological effects through inhibition of transcription factors (TFs) in addition to arrest at the replication fork, DNA strand breakage, and inhibition of enzymes including endonucleases and RNA polymerases. Hence, PBDs can be used to target specific DNA sequences to inhibit TFs as a novel anticancer therapy. Objective: To explore the ability of SJG-136 to bind to the cognate sequences of transcription factors using a previously described HPLC/MS method, to obtain preliminary mechanistic evidence of its ability to inhibit transcription factors (TF), and to determine its effect on TF-dependent gene expression. Methods: An HPLC/MS method was used to assess the kinetics and thermodynamics of adduct formation between the PBD dimer SJG-136 and the cognate recognition sequence of the TFs NF-κB, EGR-1, AP-1, and STAT3. CD spectroscopy, molecular dynamics simulations, and gene expression analyses were used to rationalize the findings of the HPLC/MS study. Results: Notable differences in the rate and extent of adduct formation were observed with different DNA sequences, which might explain the variations in cytotoxicity of SJG-136 observed across different tumour cell lines. The differences in adduct formation result in variable downregulation of several STAT3-dependent genes in the human colon carcinoma cell line HT-29 and the human breast cancer cell line MDA-MB-231. Conclusions: SJG-136 can disrupt transcription factor-mediated gene expression, which contributes to its exceptional cytotoxicity in addition to the DNA-strand cleavage initiated by its ability to crosslink DNA.

Environmental release behavior, cell toxicity and intracellular distribution of novel biodegradable plastic materials.

Environmental release behavior, cell toxicity and intracellular distribution of novel biodegradable plastic materials.

Anticancer effect of a single-chain variable fragment against pro-matrix metalloproteinase-7 in colon cancer.

Anticancer effect of a single-chain variable fragment against pro-matrix metalloproteinase-7 in colon cancer.

Tracing of Amino Acids Dynamics in Cell Lines Based on 18O Stable Isotope Labeling.

Metabolite levels and turnover rates are necessary to understand metabolomic dynamics in a living organism fully. Amino acids can play distinct roles in various cellular processes, and their abnormal levels are associated with pathological conditions, including cancer. Therefore, their levels, especially turnover rates, may provide enormous information about a phenotype. 13C- or 13C,15N-labeled amino acids have also been commonly used to trace amino acid metabolism. This study presented a new methodology based on 18O labeling for amino acids that relied on monitoring mass isotopologues to calculate the turnover rates of amino acids. The method optimization studies were carried over for selective amino acid monitoring. This methodology provides a rapid, robust, and simple GC-MS method for analyzing the fluxes of amino acid metabolism. The developed method was applied to fetal human colon (FHC) and human colon carcinoma (Caco-2) cell lines to determine cancer-induced shifts in the turnover rates of amino acids. These results defined metabolic reprogramming in Caco-2 cells through increased glutamate and serine turnovers and sharply decreased turnovers of aspartate, threonine, and methionine, therefore pointing to some metabolic vulnerabilities in the metabolism of cancerous cells. The simple mechanism of the developed methodology, the availability of affordable 18O-enriched water, and the ease of application can open a new arena in fluxomics analysis.

Evaluation of Anticancer Activity of Novel and Tumor-Targeted Glutamine-Conjugated Organotin(IV) Compounds in Colorectal Cancer─An In Vitro and In Vivo Study.

Over the years, numerous ligand-based organotin(IV) Schiff base compounds have shown remarkable cytotoxicity and anticancer activities, but their clinical use is restricted by systemic toxicity, prompting the search for targeted therapies. Targeted delivery can be enhanced by exploiting the inherent characteristics of cancer cells such as glutamine addiction, which is essential to support cellular biosynthesis and cell growth to sustain aberrant proliferation. Our previous study revealed glutamine-conjugated organotin(IV) compounds have strong DNA/protein affinities, favorable in silico ADME profiles, and significant antiproliferative activity. In this study, these compounds demonstrated significant cytotoxicity against human colon carcinoma and adenocarcinoma cell lines via the induction of cell cycle arrest and apoptosis. In DMH/DSS-induced experimental colon carcinogenesis, these compounds reduced tumor burden and volume and inhibited cell proliferation and induced apoptosis, with minimal toxicity. Tissue distribution studies revealed selective accumulation in the colon. These findings support their potential as chemotherapeutic candidates for colon cancer.

Phytochemical analysis of Diospyros buxifolia (Blume) Hiern. bark extract via LC-MS/MS and evaluation of its antiproliferative activity against human colon carcinoma cells

Bioactive phytochemicals have shown a very significant role in pharmacological ailments in humans. The literature review indicates the extensive use of Diospyros extracts for the treatment of diseases related to the oral cavity and gastrointestinal disorders. Further, the bark, fruit, and root are the most commonly utilised components in traditional preparations. Due to a lack of awareness about Diospyros buxifolia (DB) and its underutilized status, relatively few studies have been conducted on its nutraceutical potential. Hence, the present study aimed to identify bioactive compounds in DB bark extracts using liquid chromatography mass spectroscopy (LC-MS/MS) and evaluate their antiproliferative activity against human colon carcinoma cells. The LC-MS/MS chromatogram showed the presence of various phytochemical compounds such as O-Phosphoryl ethanolamine, Dulcitol, 2-(2-Aminoethyl) pyridine, Alpha-Lipoic acid, 14-(Hydroxymethyl)-5,9-dimethyltetracyclo-hexadecan-5-ol, Geranyl acetone, Retinol, Retinoids, Pimelic acid, 3-Methyl-2-oxovaleric acid sodium, and Prolinamide, etc. An extensive literature survey revealed various pharmaceutical properties. The extract demonstrated dose-dependent antiproliferative effects against HT-29 and HCT-116 cells with IC50 values of 43.5 ± 4.2 and 48 ± 3.7 µg/ml, respectively, by MTT assay. Moreover, the extract enhanced the reactive oxygen species (ROS) level, altered cellular morphology, and induced apoptosis as evaluated by fluorescence microscopy. Current findings suggest DB produces significant levels of ROS (1.8-fold), which may cause apoptosis by disrupting the balance between the oxidant and antioxidant enzyme systems to alter the redox balance in the carcinoma cells tested. Interestingly, DB at the highest concentrations significantly enhances the release of lactate dehydrogenase (2.7-fold) in HT-29 and HCT-116 cells. This result suggests the involvement of necrosis in the cytotoxic effect of DB. In conclusion, DB includes strong anticancer agents with notable antiproliferative activity, which makes it suitable for application in medicine and the food industry.

Squalene in Nanoparticles Improves Antiproliferative Effect on Human Colon Carcinoma Cells Through Apoptosis by Disturbances in Redox Balance.

Squalene, a triterpene found in extra virgin olive oil, has therapeutic properties in diseases related to oxidative stress, such as cancer. However, its hydrophobic nature and susceptibility to oxidation limit its bioavailability outside of olive oil. To expand its applications, alternative delivery methods are necessary. The objective of the present study was to examine the impact of squalene encapsulated in PLGA (poly(lactic-co-glycolic) acid) nanoparticles (PLGA + Sq) on the proliferation of human colon carcinoma Caco-2 cells, as well as its underlying mechanism of action. The findings demonstrated that PLGA + Sq exert no influence on differentiated cells; however, it is capable of reducing the proliferation of undifferentiated Caco-2 cells through apoptosis and cell cycle arrest in the G1 phase. This effect was initiated by the release of cytochrome c into the cytoplasm and the subsequent activation of caspase-3. Furthermore, squalene exhibited pro-oxidant activity, as evidenced by an increase in intracellular ROS (reactive oxygen species) levels. The results of the squalene effect on genes associated with cell death, inflammation, and the cell cycle indicate that its antiproliferative effect may be post-transcriptional. In conclusion, PLGA + Sq demonstrate an antiproliferative effect on Caco-2 cells through apoptosis by altering redox balance, suggesting squalene's potential as a functional food ingredient for colorectal cancer prevention.

Loss of Notch dimerization perturbs intestinal homeostasis by a mechanism involving HDAC activity.

A tri-protein complex containing NICD, RBPj and MAML1 binds DNA as monomer or as cooperative dimers to regulate transcription. Mice expressing Notch dimerization-deficient alleles (NDD) of Notch1 and Notch2 are sensitized to environmental insults but otherwise develop and age normally. Transcriptomic analysis of colonic spheroids uncovered no evidence of dimer-dependent target gene miss-regulation, confirmed impaired stem cell maintenance in-vitro, and discovered an elevated signature of epithelial innate immune response to symbionts, a likely underlying cause for heightened sensitivity in NDD mice. TurboID followed by quantitative nano-spray MS/MS mass-spectrometry analyses in a human colon carcinoma cell line expressing either NOTCH2DD or NOTCH2 revealed an unbalanced interactome, with reduced interaction of NOTCH2DD with the transcription machinery but relatively preserved interaction with the HDAC2 interactome suggesting modulation via cooperativity. To ask if HDAC2 activity contributes to Notch loss-of-function phenotypes, we used the HDAC2 inhibitor Valproic acid (VPA) and discovered it could prevent the intestinal consequences of NDD and gamma secretase inhibitors (DBZ or DAPT) treatment in mice and spheroids, suggesting synergy between HDAC activity and pro-differentiation program in intestinal stem cells.

Hydrogen Sulfide (H2S) Activatable Photodynamic Therapy Against Colon Cancer by Tunable FRET Effect.

Developing activatable photodynamic agents is becoming a promising mode for realizing selective photodynamic therapy (PDT) in cancer treatment. However, till now only a few H2S-activatable photodynamic agents have been involved in this field. Here, we fabricated H2S-activatable nano-assemblies (P@TPPCY) for the treatment of colon cancer containing high concentration H2S. The H2S-activatable photosensitizer (TPPCY) was synthesized by covalent conjugation between tetraphenylporphyrin (TPP) and heptamethine cyanine (Cy7), and then TPPCY was encapsulated by an amphiphilic polymer DSPE-mPEG to form P@TPPCY nano-assemblies. We demonstrated that the photosensitizing effect of TPP was efficiently quenched by Cy7 with strong absorption in the NIR region via fluorescence resonance energy transfer (FRET) effect. Interestingly, the FRET effect between Cy7 and TPP was attenuated by the decrease of absorption of Cy7 in the NIR region after the Cy7 reacted with H2S, and then the photosensitizing effect of TPP in P@TPPCY was activated. Strikingly, the P@TPPCY showed efficient H2S-activatable photodynamic therapy (PDT) in vitro against HCT116 cells (human colon carcinoma cell line), thus this work provides a new method for realizing accurate treatment of colon cancer in virtue of high H2S concentration microenvironment.

SARS-CoV-2 nucleocapsid protein interaction with YBX1 displays oncolytic properties through PKM mRNA destabilization

BackgroundSARS-CoV-2, a highly contagious coronavirus, is responsible for the global pandemic of COVID-19 in 2019. Currently, it remains uncertain whether SARS-CoV-2 possesses oncogenic or oncolytic potential in influencing tumor progression. Therefore, it is important to evaluate the clinical and functional role of SARS-CoV-2 on tumor progression.MethodsHere, we integrated bioinformatic analysis of COVID-19 RNA-seq data from the GEO database and performed functional studies to explore the regulatory role of SARS-CoV-2 in solid tumor progression, including lung, colon, kidney and liver cancer.ResultsOur results demonstrate that infection with SARS-CoV-2 is associated with a decreased expression of genes associated with cancer proliferation and metastasis in lung tissues from patients diagnosed with COVID-19. Several cancer proliferation or metastasis related genes were frequently downregulated in SARS-CoV-2 infected intestinal organoids and human colon carcinoma cells. In vivo and in vitro studies revealed that SARS-CoV-2 nucleocapsid (N) protein inhibits colon and kidney tumor growth and metastasis through the N-terminal (NTD) and the C-terminal domain (CTD). The molecular mechanism indicates that the N protein of SARS-CoV-2 interacts with YBX1, resulting in the recruitment of PKM mRNA into stress granules mediated by G3BP1. This process ultimately destabilizes PKM expression and suppresses glycolysis.ConclusionOur study reveals a new function of SARS-CoV-2 nucleocapsid protein on tumor progression.

Anticancer Activity In Vitro of Sulfated Polysaccharides from the Brown Alga Spatoglossum vietnamense.

Sulfated polysaccharides SpvF1, SpvF2, SpvF3, and SpvF4 from the brown alga S. vietnamense collected north of Hon Do (Nha Trang Bay, Vietnam) were isolated and studied. The structure of the obtained polysaccharide was studied using chemical methods and NMR spectroscopy. Fucoidans were low-sulfated (SpvF1, SpvF2) and medium-sulfated (SpvF3, SpvF4) heterogeneous polysaccharides. The molecular weight of the polysaccharides obtained was in the range of 16 to 44 kDa. All investigated fucoidans until 400 µg/mL were not cytotoxic for human colon carcinoma cells DLD-1, HCT-116, and HT-29 in vitro. Fucoidans SpvF1 and SpvF2 have inhibited the colony formation and growth of investigated cells from 20 to 30%. Fucoidans SpvF3 and SpvF4 have the strongest inhibitory effect for investigated cancer cells: from 40 to 50%.

SIRT2 deacetylates and decreases the expression of FOXM1 in colon cancer.

New FOXM1-specific inhibitors with the potential to be used for therapeutic purposes are under extensive research. We hypothesized that deacetylation of FOXM1 would decrease protein expression, thus providing novel therapeutic management of colon cancers. Immunostaining was used to determine FOXM1 and SIRT2 expressions in human colon cancer tissue microarrays (n = 90) from Stage I to Stage IV. SIRT2-FOXM1 interaction was evaluated in colon cancer cells using immunoprecipitation. Deacetylation of FOXM1 via SIRT2 was determined using in vitro deacetylation assays. FOXM1 could be hyper-acetylated when p300 and pCAF histone acetyltransferases were administered alongside deacetylase inhibitors. We detected that SIRT2 and FOXM1 physically interacted, and SIRT2 deacetylated FOXM1 in vitro. SIRT2 overexpression led to a significant decrease while knockdown of SIRT2 increased the FOXM1 expression in HCT116 human colon carcinoma cells. In the analysis of 90 human colorectal cancer samples, high SIRT2 expression was observed in about 49% of colorectal cancer, intermediate in 29%, and low or no staining in 22%. Strong SIRT2 expression was found to be negatively associated with the FOXM1 staining in our clinical cohort. This study reveals a molecular interaction and association between SIRT2 and FOXM1 expression in colon cancer cell lines and human colon cancer samples, and suggests that targeting SIRT2 activity using small molecule modulators may be a promising therapeutic approach for colorectal cancer.

Curcuminoid Chalcones: Synthesis and Biological Activity against the Human Colon Carcinoma (Caco-2) Cell Line.

There are many current scientific reports on the synthesis of various derivatives modelled on the structure of known small-molecular and natural bioactive compounds. Curcuminoid chalcones are an innovative class of compounds with significant therapeutic potential against various diseases and they perfectly fit into the current trends in the search for new biologically active substances. The aim of this study was to design and synthesise a series of curcuminoid chalcones. The objective of this scientific paper was to synthesise twelve curcuminoid chalcones and confirm their structures using spectral methods. Additionally, the biological activity of three of the synthesised compounds was evaluated using various assays, and their anticancer properties and toxicity were studied. The proposed derivatives were obtained via the Claisen-Schmidt reaction of selected acetophenones and aldehydes in various conditions using both classical methods: the solutions and solvent-free microwave (MW) or ultrasound (US) variants. The most optimal synthetic method for the selected curcuminoid chalcones was the classical Claisen-Schmidt condensation in an alkaline (NaOH) medium. Spectral methods were used to confirm the structures of the compounds. The resazurin reduction assay, caspase-3 activity assay, and RT-qPCR method were performed, followed by measurements of the intracellular reactive oxygen species (ROS) level and the lactate dehydrogenase (LDH) release level. Twelve designed curcuminoid chalcones were successfully synthesized and structurally confirmed by NMR, MS, and IR spectroscopy. Examination of the anticancer activity was carried out for the three most interesting chalcone products. The results suggested that compound 3a increased the metabolism and/or proliferation of the human colon carcinoma (Caco-2) cell line, while compounds 3b and 3f showed significant toxicity against the Caco-2 cell line. Overall, the preliminary results suggested that compound 3b exhibited the most favourable anticancer activity.

Chemical Profiling and Cytotoxicity Activity of Essential Oil from Artemisia Maritima Collected through Four Different Wild Locations of Lahaul Valley in Indian Western Himalaya

AbstractThis research leads to the analysis of quality parameters and chemical profiles of Artemisia maritima essential oils (EOs) extracted from four different wild areas viz: Darcha, Jispa, Gemur and Tandi of Lahaul valley of Indian western Himalaya in comparison to a market sample. The EOs content was found higher in Darcha (0.54 %) and Jispa (0.48 %). The quality parameters such as color, odor, density, refractive index and optical rotations were found comparable with the market sample. Further, volatile chemo‐profile of EOs was generated using GC/GC‐MS. A total of 34 metabolites were identified in five samples (n=3) that account around 87.3–95.1 % of the total oils. These EOs majorly contained monoterpene hydrocarbons (3.0–68.5 %) and oxygenated monoterpenes (26.6–85.0 %) with β‐myrcene (9.8–20.6 %), α‐terpinene (0.7–17.3 %), β‐phellandrene (1.5–22.4 %), 1,8‐cineole (3.0–50.8 %), terpinen‐4‐ol (2.5–7.2 %), ascaridole (11.5 %), bornyl acetate (5.1–14.2 %), trans‐sabinyl acetate (0.8–49.6) and trans‐ascaridole (7.9 %). Moreover, cytotoxicity study of EOs against CaCo2 and HT‐29 human colon carcinoma cell lines unveiled significant anticancer potential of A. maritima. AMD (82.87±0.39 %) AMG (61.17±1.45 %) and AMM (73.37±2.1 %) showed comparable activity at 600 μg/ml (72 hr) in comparisons to vinblastine (20 μM). A. maritima is less explored as compared to other species and could be a new potential source for EOs and anticancer candidate.