SW480 Cell Lines Research Articles

LncRNA DANCR-V1 is a novel regulator of Wnt/β-catenin and TGF-β1/SMAD signaling pathways in colorectal cancer: an in vitro and in silico study.

DANCR is an oncogenic lncRNA associated with advanced colorectal cancer, one of the most common malignancies worldwide. This lncRNA has a new variant, DANCR-V1, whose function is not yet understood. In this study, we aimed to evaluate the expression pattern of DANCR-V1 and its regulatory mechanism in colorectal cancer. Bioinformatics analysis and RT-qPCR showed that DANCR-V1 expression was higher in colorectal cancer tissues than in normal pairs obtained from microarray data and 20 samples, respectively. LncRNA subcellular localization and hsa-miR-222 binding sites were predicted using bioinformatics tools. Dual luciferase assays confirmed that miR-222-mediated downregulation of DANCR-V1 through its targeting, and RT-qPCR showed that overexpression of miR-222 decreased the level of DANCR-V1. Functionally, Wnt/β-catenin and TGF-β1/SMAD-related genes changed under DANCR-V1 overexpression in the SW480 cell line, while their expression was reversed following miR-222 overexpression. Finally, at the cellular level, overexpression of DANCR-V1 elevated the proliferation and migration rates of SW480 cells, as determined using flow cytometry, western blotting and scratch assays. Our data suggest that DANCR-V1 is a novel transcript variant that has crucial crosstalk with miR-222 via negative feedback and plays a critical role in colorectal cancer progression through Wnt/β-catenin and TGF-β1/SMAD signaling modulation.

Extracellular nicotinamide phosphoribosyltransferase visfatin activates JAK2-STAT3 pathway in cancer-associated fibroblasts to promote colorectal cancer metastasis.

Metastasis is one of the major challenges in the treatment of colorectal cancer (CRC), during which cancer-associated fibroblasts (CAFs) in the tumor microenvironment are critically involved. In this study, we aim to explore the regulatory role of extracellular nicotinamide phosphoribosyltransferase Visfatin and its impact on CRC metastasis. To examine the effect of visfatin on CAFs, human CRC tissue-derived CAFs were exposed to visfatin, and the expression of inflammatory factors, activation of JAK-STAT pathway and production of ROS in CAFs were assessed. To examine the effect of visfatin-treated CAFs on CRC metastasis, human CRC cell line SW480 or SW620 were cultured with the conditioned medium derived from visfatin-treated CAFs, and the invasion and migration ability of SW480 or SW620 cells were evaluated by transwell migration and matrigel invasion assays. Our previous study found that visfatin, a secreted form of nicotinamide phosphoribosyltransferase that governs the rate-limiting step of NAD synthesis, promoted CRC metastasis. However, little is known about the effect of visfatin on CAFs. The conditioned medium derived from visfatin- treated CAFs promotes the migratory and invasive capability of CRC cells, and enhance lung metastasis in mouse model. Visfatin treatment stimulated the expression of a couple of inflammatory factors in CAFs, which was mediated by visfatin-induced activation of JAK- STAT pathway and accumulation of ROS. Inhibition of JAK-STAT pathway or neutralization of cellular ROS attenuated visfatin-mediated migration and invasion of CRC cells. The present work highlights a critical role of visfatin in the crosstalk between CRC cells and CAFs, which moonlight as a non-metabolic extracellular signal molecule to hijacks JAK-STAT pathway in CAFs to promote CRC metastasis.

Cytochalasins and orsellinic acid derivatives with cytotoxicity from the soil-derived fungus Trichocladium asperum

Four undescribed cytochalasins (1−4), three undescribed orsellinic acid derivatives (5−7) and two known metabolites including methyl lecanorate (8) and methyl orsellinate (9) were isolated from the solid-state cultivation of a soil-derived fungus Trichocladium asperum SQ2-3 collected in Qinghai-Tibet Plateau. Their structures were elucidated by analysis of NMR (1D and 2D) and mass spectrometry data. The absolute configurations of 1−7 were assigned by a combination of the modified Mosher's method, microscale derivatization and Mo2(OAc)4-induced circular dichroism experiment. Compounds 1, 2, 3 and 6 showed significant cytotoxicity against HL-60, A3494, SMMC-7721, MDA-MB-231 and SW480 cell lines with IC50 values ranging from 4.74 to 15.84 μM, respectively. Meanwhile, compound 1 could obviously damage mitochondrial membrane potential and induce G2/M cell cycle arrest in A549 cells.

Methyltransferase-like 14 promotes the tumorigenesis and proliferation of pancreatic cancer cells through myc proto-oncogene signaling pathway

Objective: Pancreatic cancer is characterized by low survival rate and rapid deterioration. Methyltransferase-like 14 (METTL14), as N6-methyladenosine (m6A) methyltransferase, is closely related to tumor progression. The purpose of this study is to look into how METTL14 affects pancreatic cancer tumorigenesis, cell division, and apoptosis. Material and Methods: We examined and contrasted the levels of METTL14 protein and messenger RNA expression in human pancreatic ductal cells and human pancreatic cancer cells. After silencing or upregulating METTL14, the proliferative ability, migration ability, and cell apoptosis of pancreatic tumor cells was detected by colony-forming assay, wound scratch healing assay, cell counting kit 8 assay, and terminal deoxynucleotidyl transferasemediated 2’-deoxyuridine 5’-triphosphate-biotin nick end labeling assay. Following the use of c-Myc inhibitor (10058-F4), western blot analysis was carried out to investigate the key factor expression and c-Myc signaling pathway activation status. Results: METTL14 was preferentially expressed in human pancreatic cancer cells PANC-1 and SW1990 than in human normal pancreatic duct cells human pancreatic nestin-expressing cells (HPNE) (P < 0.001). Overexpression of METTL14 increased the tumorigenic and proliferative ability of pancreatic cancer cells. Overexpression of METTL14 decreased apoptosis rate. Western blot assay showed that nucleus b-catenin increased when METTL14 was overexpressed, and nucleus b-catenin decreased when METTL14 was silenced in PANC-1 cell (P < 0.01). The protein expression of other key factors, such as c-Myc, matrix metalloproteinase (MMP)-9, and MMP-2, were also affected. The use of c-Myc inhibitor (10058-F4) on the basis of OE-METTL14 reversed the effect of the overexpression of METTL14 on promoting the tumorigenesis and cell proliferation of pancreatic cancer cell lines PANC-1 and SW1990. Conclusion: METTL14 promoted the tumorigenesis and proliferation of pancreatic cancer cells by the c-Myc signaling pathway.

Decreased mitochondrial transcription factor A and mitochondrial DNA copy number promote cyclin-dependent kinase inhibitor 1A expression and reduce tumorigenic properties of colorectal cancer cells

PurposeColorectal cancer is one of the most common and deadliest cancer types worldwide. In the last years, changes in the mitochondrial DNA (mtDNA) copy number have been described to correlate with the prognostic outcome for colorectal cancer patients by impacting different tumorigenic properties. One key regulator of mtDNA is the mitochondrial transcription factor A (TFAM) that acts as a limiting factor of mtDNA copy number. Here, we investigated the effect of TFAM deficiency on mtDNA and tumorigenic properties in the human colorectal cancer cell line SW480.MethodsTFAM expression was stably downregulated in the colorectal cancer cell line SW480 using the CRISPR-Cas9 approach. To dissect the molecular alterations induced by deletion of TFAM, RNA sequencing and gene set enrichment analysis was performed on TFAM-wild-type and TFAM-deficient SW480 cells. Functional consequences of TFAM downregulation were assessed in cellular assays.ResultsWe showed that TFAM deficiency leads to decreased mtDNA copy number and reduced expression of mtDNA-encoded genes. TFAM-deficient cells also revealed higher activity of senescence-associated β-galactosidase and decreased cell growth parameters. Moreover, RNA sequencing showed that the expression of cyclin dependent kinase inhibitor 1A (CDKN1A/p21) is significantly increased in TFAM-deficient cells.ConclusionOur results suggest that TFAM-induced changes of the mitochondrial genome lead to upregulated CDKN1A/p21 expression in colorectal cancer cells identifying p21 as a new possible linker between mitochondria and nucleus.

Fibroblast-like synoviocyte targeting antibodies are associated with failure to reach early and sustained remission or low disease activity after first-line therapy in rheumatoid arthritis

ObjectiveTo discover antibody biomarkers that can predict a lack of response to first-line therapy in rheumatoid arthritis (RA) patients.MethodsTwo RA cDNA phage display libraries were screened for novel antibodies in baseline RA sera from the Care in early RA (CareRA) trial, differentiating between patients who did or did not reach remission after first-line therapy (n=20 each). Antibody reactivity to identified University Hasselt (UH)-RA antigens was validated in baseline samples from 136 additional CareRA participants. The novel antibodies’ potential to predict failure to reach remission or low disease activity (LDA), according to the Disease Activity Score 28-joint C-reactive protein/erythrocyte sedimentation rate (DAS28CRP/ESR) and Clinical/Simplified Disease Activity Index (CDAI/SDAI), was studied by multivariate analyses. The presence of the antibody targets in RA synovial tissue and the fibroblast-like synoviocyte (FLS) cell line SW982 was determined by immunofluorescence.ResultsWe identified antibodies to 41 novel antigens. Antibodies against any of three antigens, UH-RA.305/318/329, discriminated between RA patients not reaching week (w)8 DAS28CRP remission and those that did (36% vs 13%,p=0.0031). In all patients, anti-UH-RA.305/318/329 antibody reactivity was associated with failure to reach week 8 DAS28CRP and DAS28ESR remission (OR 3.63,p=0.0031; OR 2.92,p=0.016; respectively), SDAI/CDAI sustained remission (OR 5.59,p=0.039 for both) and DAS28CRP and DAS28ESR sustained LDA (OR 3.7,p=0.009; OR 2.76,p=0.042; respectively). In rheumatoid factor/anti-citrullinated protein antibody (RF/ACPA) seronegative patients, these antibodies were strongly associated with failure to achieve week 8 DAS28CRP remission (OR 17.3,p=0.0029). Anti-UH-RA.305/329 antibodies were shown to target FLS in RA synovial tissue and SW982 cells.ConclusionWe identified three antibody biomarkers that are associated with failure to achieve remission/LDA after first-line RA therapy.

Preparation of a new reusable magnetic organocatalyst to synthesis of polyhydroquinoline derivatives as cytotoxic Agents: Synthesis and biological evaluation

One of the most important ways to practice environmental stewardship is to turn waste materials into useful nanomaterials through ecological recycling. This work introduces a magnetic organocatalyst made from red mud waste, adding to the “greening” of global chemical processes.The new composite (Fe3O4@SiO2@(CH2)3@4-(2-Aminoethyl)-morpholine) is introduced and characterized by different spectroscopic methods such as fourier transform infrared (FT-IR), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), mapping, thermogravimetric analysis (TGA) and vibrating-sample magnetometers (VSM). Catalytic activity of the catalyst was evaluated in production of some polyhydroquinoline derivatives and the results showed efficiency. Nine polyhydroquinoline derivatives were synthesized (M1-M9) and their cytotoxic properties evaluated against two human-cancerous cell lines (Hep-G2 and SW480) by MTT assay. Most of the compounds exhibited high inhibitory activity against two studied cell lines. M2 bearing 2-chloro substitution on phenyl ring was exhibited appropriate activity (IC50 = 14.70 ± 3.11 µM) against SW480 cell line in comparison to cisplatin as positive control.

PTPN11 is a potential biomarker for type 2 diabetes mellitus complicated with colorectal cancer

Epidemiological surveys have shown that the incidence of type 2 diabetes mellitus (T2DM) and malignancies is rapidly increasing worldwide and has become a major disease that threatens human life. In this study, we quantitatively analyzed the proteome of tumor tissues and adjacent normal tissues from six patients withT2DM combined with colorectal cancer (CRC) and eight non-diabetic CRC, focusing on the effect of T2DM on tumor tissues. We analyzed the functional enrichment of differentially expressed proteins (DEPs) using clusterProfiler in R and the expression level of protein tyrosine phosphatase non-receptor type 11 (PTPN11) and other key proteins in the TIMER and GEPIA2 databases. The HPA database was used to validate PTPN11 protein expression. The correlation between PTPN11 expression and clinicopathological features was analyzed by UALCAN database. The impact of PTPN11 on clinical prognosis was evaluated utilizing Kaplan-Meier Plotter. The correlation between PTPN11 expression and tumor-infiltrated immune cells was investigated via TIMER and TISIDB databases. Gene set enrichment analysis (GSEA) was performed to examined the pathway of PTPN11 enrichment in CRC using data from The Cancer Genome Atlas (TCGA) database. Furthermore, small interfering (si) RNA was used to knock down PTPN11 in CRC cell line SW480. Western blot analysis was used to detect PTPN11 expression in tissue samples or cells and the effect of PTPN11 knockdown on key proteins related to PI3K/AKT and cell cycle pathway in SW480 cells. Cell proliferation and wound healing assays were used to detect the effects of cell proliferation and migration after knockdown of PTPN11 or treatment with high glucose. We found that metabolic pathways such as oxidative phosphorylation, glycolysis/gluconeogenesis, and insulin secretion were significantly enriched in tumor tissues from diabetic patients compared to non-diabetic patients. In addition, PTPN11, a marker gene associated with T2DM and CRC, were mined in diabetic tumor tissues. PTPN11 showed high expression in diabetic tumor tissues compared to normal tissues. High PTPN11 expression predicted poor prognosis in CRC. PTPN11 expression was strongly associated with immune infiltrating cells in CRC. GSEA analysis revealed that PTPN11 was enriched in cancer-related pathways. Western blotting analysis indicated that PTPN11 knockdown reduced the protein levels of p-PI3K, p-AKT, CDK1 and CYCLIN D, without altering PI3K and AKT protein levels. Cell proliferation and wound healing data showed that PTPN11 and high glucose could increase the proliferation and migration ability. These findings showed that PTPN11 may be a potential key biomarker for CRC in patients with diabetes, which will provide new potential targets for future intervention of T2DM complicated with CRC.

A novel normonoterpene glycoside and a new benzophenone derivative from Hypericum cerastioides and their in vitro cytotoxic activities

Phytochemical investigations on the aerial parts of Hypericum cerastioides led to the isolation and identification of a novel normonoterpene (1) and a previously undescribed benzophenone glycoside (3) along with eleven known secondary metabolites (2, 4–13). Their structures were deduced based on extensive 1D and 2D NMR analyses as well as HRESIMS. Compound 1 is a rare type of normonoterpene derivative with eight carbon atoms. The chemotaxonomic significance of the isolates was also discussed. Compounds were evaluated for their in vitro cytotoxic activities against SW480, A375, DU145 and MCF7 cancer cell lines using doxorubicin as a reference drug. Compounds 1 and 7 demonstrated weak cytotoxicity.

Bipolaristeroid A, a 5,6-seco-9,10-seco-steroid with cytotoxic activity from the fungus Bipolaris maydis

Eleven undescribed steroids, bipolaristeroids A–K, and one known compound, demethylincisterol A3, were isolated from the fungus Bipolaris maydis. Bipolaristeroid A is a 5,6-seco-9,10-seco-steroid with a rearranged B ring, in which the A and C rings are connected by an ester bond. Bipolaristeroid B is a rearranged 1(10 → 6)-abeosteroid with an aromatic B ring. Their planar structures and absolute configuration were determined using NMR, HRESIMS, DP4+ analysis, ECD calculation, and single-crystal X-ray diffraction. Bipolaristeroid A shows excellent inhibitory effects against the cancer cell lines HepG2, A549, SW620, and C4–2B with IC50 values of 7.94, 5.11, 5.13, and 3.83 μM, respectively.

Multi-omics analyses were combined to construct ubiquitination-related features in colon adenocarcinoma and identify ASNS as a novel biomarker.

As one of the malignant tumors with the highest incidence and fatality in the world, colon adenocarcinoma (COAD) has a very complex pathogenic mechanism, which has not yet been fully elucidated. Ubiquitin can regulate cell proliferation, cell cycle, apoptosis, DNA damage repair, and other processes by changing the activity of substrate proteins or causing ubiquitin-proteasome degradation. These are the key links in the pathogenesis of COAD, and ubiquitin plays an important role in the occurrence and development of COAD. We integrated transcriptomics, single-cell and clinical omics, and TCGA and GEO databases of COAD patient data. Cox and Lasso regression was employed to assess ubiquitination genes in COAD for generating ubiquitination-related features. The aim was to evaluate the prognostic value of these features for tumors and their impact on the immune microenvironment. At the same time, the expression level of model genes was further analyzed using single-cell data. Finally, the expression and function of ASNS, a key gene for this trait, were detected in vitro. In our study, based on identifiable changes in the expression of marker genes, this feature can be used to classify patients with COAD. Kaplan-Meier survival analysis indicated that those with elevated risk scores in each cohort experienced inferior outcomes. There is good validation in both the training queue and the validation queue. The results of the immune infiltration analysis showed that the immune infiltration rate was significantly increased in the high-risk group. After the knockdown of ASNS, an important gene in the signature, the activity and migration capacity of SW620 and RKO cell lines and colony formation capacity were dramatically reduced in cell tests. We screened ubiquitination-related genes and constructed ubiquitination-related features, which can be used as reliable prognostic indicators of COAD. ASNS was identified as a possible biomarker for COAD.

Synthesis of New Fluorinated Tubastatin A Derivatives Based on Cyclopentane/Cyclohexane with Good Anti‐tumor Activity in Vitro

AbstractTwo series of novel fluorinated Tubastatin A derivatives based on cyclopentane or cyclohexane substitution were first time synthesized by 5 steps at high yield. The influence of the cycloalkanes substituted N‐methylpiperidine and/or fluorinated group on the cap group of Tubastatin A for the in vitro anti‐tumor activity of seven different tumor cell lines (human hepatoma cells Bel7402 and HepG2, human nasopharyngeal carcinoma cells CNE2 and SUNE1, human breast cancer cells MDA‐MB‐231 and MCF‐7, and human pancreatic cancer cells SW1990) was investigated. Compared with Tubastatin A, these novel derivatives with fluorinated groups on the benzene ring of the cap group enhance activity, and modification of the N‐methylpiperidine to cycloalkanes of the cap group improves solubility. The most promising compound trifluoromethyl and cyclohexane substituted derivative, N‐hydroxy‐4‐((6‐(trifluoromethyl)‐1,2,3,4‐tetrahydro‐9H‐carbazol‐9‐yl)methyl) benza‐mide (6 h), had a wide range of anti‐tumor cell range, the IC50 value for human pancreatic cancer cell line SW1990 was 1.17 μM. Hence, fluorinated groups and cyclohexane result in a wide range of anti‐tumor cell range and good anti‐cancer activity.

Enhancing the Cytotoxicity and Apoptotic Efficacy of Parasporin-2-Derived Variants (Mpp46Aa1) on Cancer Cell Lines.

Parasporin PS2Aa1, recently renamed Mpp46Aa1, is an anti-cancer protein known for its selectivity against various human cancer cell lines. We genetically modified native PS2Aa1 to create a library of approximately 100 mutants. From this library, we selected promising mutants based on their half-maximal inhibitory concentration (IC50) and sequence variations. In this study, Variant 3-35, with the G257V substitution, demonstrated increased cytotoxicity and selectivity against the colon cancer cell line SW480. Conversely, Variant N65, featuring substitutions N92D, K175R, and S218G, yielded the most favorable results against the cancer cell lines SW-620, MOLT-4, and Jurkat. The caspase 3/7 and 9, Annexin V-Cy3 and 6-GFDA activities, and, most notably, mitochondrial membrane permeabilization assays confirmed the apoptotic marker elevation. These findings indicate that residues 92, 175, 218, and 257 may play a critical role in the cytotoxic activity and selectivity. We successfully obtained genetically improved variants with substitutions at these key amino acid positions. Additionally, we conducted molecular dynamic simulations to explore the potential interactions between PS2Aa1 and the CD59 GPI-anchored protein. The simulation results revealed that residues 57, 92, and 101 were consistently present, suggesting their possible significance in the interactions between parasporin and the CD59 protein.

Characterization of the AGR2-NPM3 axis uncovers the AGR2 involvement in PD-L1 regulation in colorectal cancer

Despite extensive research, the molecular role of AGR2 in the progression and metastasis of colorectal cancer (CRC) has not been fully characterized. We used quantitative mass spectrometry (SWATH MS) to identify differentially expressed proteins in paired CRC cell models of the SW480 and SW620 cell lines in response to AGR2 protein level manipulation. Relying on the results from SWATH MS and subsequent immunochemical validation, we selected NMP3 as the top candidate protein associated with AGR2 in CRC tumour cells in our screen. RT‒qPCR and immunochemical analysis confirmed the involvement of AGR2-mediated regulation of NPM3 at the transcriptional and posttranscriptional levels. Since PD-L1 is a constituent of the NPM3 regulatory axis, we aimed to correlate the changes in PD-L1 to the differential expression of AGR2 in our cell models. We found that AGR2 positively regulates PD-L1 levels in both SW480 and SW620 cell lines; additionally, several different CRC patient transcriptome cohorts confirmed the association of AGR2 with PD-L1. Our work reveals a new AGR2-NPM3 regulatory axis and the involvement of AGR2 in the regulation of PD-L1, which paves the way for the association of AGR2 with immune evasion in CRC cells.

Cytotoxic effect of Trigonella coerulescens subsp. ayvalikensis Erdoğan, Selvi & Tümen in prostate and colon cancer cell lines

Trigonella coerulescens subsp. ayvalikensis is an annual local endemic taxon distributed only in Ayvalık/Balıkesir district and evaluated in the Vulnerable Category (VU). Trigonella L. is an important genus with medicinal and economic value in the Fabaceae family. Seeds of the genus Trigonella are known to contain several groups of secondary metabolites, the most abundant compounds being steroidal saponins, as well as flavones, isoflavones, and polysaccharides. In our study, the cytotoxic effect on two different cancer cell lines namely, PC-3 (prostate) and SW480 (colon), was investigated by extracting Trigonella coerulescens subsp. ayvalikensis with different solvents. The cytotoxic effects of extracts obtained from plant seeds with different solvents (hexane, methanol, ethanol, acetone) were investigated. The MTT test was used to examine the cytotoxic effect, which was studied with PC-3 and SW480 cancer cell lines. The different concentrations (23.45 µg/µL, 46.875 µg/µL, 93.75 µg/µL, 187.5 µg/µL, 375 µg/µL) of seed extracts were applied to the cells at different times points (24h, 48h and 72h) and absorbance was taken at 550 nm in the spectrophotometer. As a result of cytotoxic studies, it was observed that hexane extract had the most reducing effect on PC-3 compared to the control groups. In the SW480 cell line, a proliferative effect was observed in extracts prepared with methanol, hexane, and acetone in the early period of 24 hours. In the later period (72 hours), the extract prepared with hexane and acetone showed the most cytotoxic effect on SW480 cells.

The anticancer effects of Aronia berry extract are mediated by Chk1 and p53 in colorectal cancer

BackgroundAronia berry extracts (ABE) have recently been reported to possess significant anti-cancer effects in various malignancies, including colorectal cancer (CRC), due to their high polyphenolic content. However, the molecular mechanism(s) underlying the anti-cancer effects of ABE in CRC remain unclear, which is important to consider when considering their use as complementary medicine approaches in cancer. MethodsWe performed genome-wide transcriptomic profiling and pathway enrichment analysis to identify specific growth signaling pathways associated with ABE treatment in CRC cells. In addition, a series of systematic and comprehensive cell culture studies were performed to investigate the anti-cancer effects of ABE in SW480 and HCT116 CRC cell lines. Subsequently, these findings were validated in patient-derived 3D organoids (PDOs) models. ResultsTranscriptomic profiling analysis identified p53 signaling as one of the key enriched pathways mediating the anti-cancer activity of ABE. Analysis of public datasets revealed that Chk1, a key regulator of p53, was one of the critical targets of ABE in CRC. Chk1 and p53 activation was shown to be downregulated with ABE treatment, leading to the induction of cell cycle arrest (p = 0.003–0.014) and enhanced DNA damage (p = 0.015–0.026). Furthermore, these findings were validated in PDOs, where the ABE treatment resulted in significantly fewer and smaller PDOs in a concentration-dependent manner (p = 0.045 - <0.001). ConclusionsWe firstly provide evidence for the role of the p53 signaling pathway as a mediator of the anti-cancer activity of ABE, which provides a rationale for its use as a safe and effective integrative medicine approach in CRC.

Morchella conica, Morchella esculenta and Morchella delicosa Induce Apoptosis in Breast and Colon Cancer Cell Lines via Pro-apoptotic and Anti-apoptotic Regulation.

To explore the potential apoptotic mechanisms of 3 Morchella extracts (Morchella conica, Morchella esculenta and Morchella delicosa) on breast and colon cancer cell lines using apoptotic biomarkers. Human breast cell line (MCF-7) and colon cancer cell line (SW-480) were treated with methanol and ethanol extracts of 3 Morchella species with concentration ranging from 0.0625 to 2 mg/mL. After that their effects on gene expression of apoptosis related markers (pro-apoptotic markers including Bax, caspase-3, caspase-7, and caspase-9, and the antiapoptotic marker including Bcl-2) were determined using reverse transcription polymerase chain reaction. All Morchella extracts reduced breast and colon cancer cells proliferation at half inhibitory concentration (IC50) of 0.02 ±0.01 to 0.68 ±0.30 mg/mL. As expected, all Morchella extracts significantly increased gene expressions of Bax, caspase-3, caspase-7, and caspase-9 and downregulated the gene expression of Bcl-2 in MCF-7 and SW-480 cell lines (P<0.05). Morchella extracts demonstrated significant anti-proliferative activity against breast and colon cancer cell lines via an apoptosis induction mechanism. Anticancer activity of Morchella extracts and activation of apoptosis in breast and colon cancer cells suggest that it may be used to develop chemotherapeutic agents against cancer in future.

Tillandsia usneoides Ethanolic Extract Induces Cytotoxicity in SW480 Colon Cancer Cell Line via PPARγ Modulation

Colorectal cancer (CRC) is a prevalent and deadly tumor worldwide. Understanding the molecular mechanisms underlying CRC development will improve treatment outcomes and patient survival. Natural molecules and metabolites from plants, such as Tillandsia usneoides, reduce tumor growth by modulating glucose metabolism and increasing reactive oxygen species (ROS). To shed light on the mechanism involved in the anti-tumor effects of T. usneoides, we evaluated the cytotoxic effect of the ethanolic extract of this plant on the colon cancer cell line SW480 through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor that plays a role on lipid metabolism and inflammation in cancer cells. To this end, we assessed the activation of PPARγ by T. usneoides extract in transactivation luciferase assays, as well as the cytotoxic effect of this extract on the SW480 cell line after knocking down PPARγ using shRNA. Our findings indicate that the T. usneoides extract exhibits cytotoxic effects on the SW480 cell line, potentially in the same way as PPARγ activator, pioglitazone, i.e., by increasing reactive oxygen species (ROS). In addition, both T. usneoides extract and pioglitazone exert lipogenic properties in the SW480 cells. Taken together, these results demonstrate that the T. usneoides extract decreases the viability of the colon cancer cell line SW480, at least in part, through the activation of PPARγ. This suggests the potential for further use of this plant in the treatment of other chronic diseases.

The Influence of Betulin and Its Derivatives on Selected Colorectal Cancer Cell Lines' Viability and Their Antioxidant Systems.

Oxidative stress is considered one of the main reasons for the development of colorectal cancer (CRC). Depending on the stage of the disease, variable activity of the main antioxidant enzymes, i.e., superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), is observed. Due to limited treatment methods for CRC, new substances with potential antitumor activity targeting pathways related to oxidative stress are currently being sought, with substances of natural origin, including betulin, leading the way. The betulin molecule is chemically modified to obtain new derivatives with improved pharmacokinetic properties and higher biological activity. The aim of this study was to evaluate the effects of betulin and its new derivatives on viability and major antioxidant systems in colorectal cancer cell lines. The study showed that betulin and its derivative EB5 affect the antioxidant enzyme activity to varying degrees at both the protein and mRNA levels. The SW1116 cell line is more resistant to the tested compounds than RKO, which may be due to differences in the genetic and epigenetic profiles of these lines.

Design, synthesis and biological evaluation of artesunate-Se derivatives as anticancer agents by inducing GPX4-mediated ferroptosis

A series of organoselenium compounds based on the hybridization of artesunate (ART) scaffolds and Se functionalities (–SeCN and –SeCF3) were synthesized. The redox properties of artesunate-SeCN and artesunate-SeCF3 derivatives were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), and the results showed that compounds 2c, 2f and 3e have a good free radical scavenging activity. Their cytotoxicity was evaluated against four types of cancer cell lines, SW480 (human colon adenocarcinoma cells), HCT116 (human colorectal adenocarcinoma cells), HepG2 (human hepatocellular carcinoma cells), MCF-7 (human breast cancer cells). The MTT results showed that compared with ART and 5-FU, compound 2c exhibited potent in vitro antiproliferative activity in SW480, HCT116, and MCF-7 cancer cell lines, and was thus chose for further antitumor mechanism investigation. The antitumor mechanism study revealed that compound 2c induced ferroptosis in HCT116 cells by inhibiting the expression of GPX4 protein, accompanying by the up-regulation of intracellular ROS levels. Mitochondria in HCT116 cells exhibit depolarization of mitochondrial membrane potential (MMP) and ultrastructural changes in morphology, which indicated that 2c resulted in mitochondrial dysfunction and ferroptosis. Moreover, 2c could increase the levels of lipid peroxidation and ferrous ion, which further confirm that compound 2c may exert its antitumor effect through ferroptosis. Overall, these results suggest that the artesunate-Se candidates could provide promising new lead derivatives for further potential anticancer drug development.