Apoptosis In Colon Cancer Cells Research Articles

Phytochemical examination of Cistus laurifolius extract and its impact on cytotoxicity, apoptosis and oxidative stress in colorectal and breast cancer cell lines

IntroductionColon and breast cancer are the most common types of cancer worldwide. This study investigatesd the anticancer properties of Cistus laurifolius L. leaf extract on breast cancer (MCF-7) and human colon cancer (Caco-2) cell lines. MethodsThe research involved meticulous collection, drying and processing of C. laurifolius leaves to extract bioactive compounds, subsequently analyzed for phenolic content using advanced LC-MS/MS technology. Cell viability of the extract on MCF-7 and Caco-2 cells was demonstrated by MTT test. Levels of critical apoptotic markers (Bad, Bax/Bcl-2, Bax/Bcl-xl, Caspase-9) and Total Antioxidant Capacity (TAC) and Total Oxidant Capacity (TOC), which affect the antioxidant system, were evaluated by the ELISA method. Identification of phenolic compounds, including quercetin and rutin, through target prediction analysis enriches our understanding of bioactive molecules. ResultsThe results of the study showed that C. laurifolius extract inhibited cell proliferation time and dose-dependent on Caco-2 and MCF-7 cells (P<0.05). TAC, Bax/Bcl-2 and Bax/Bcl-xl ratios in MCF-7 and Caco-2 cells increased in a dose-dependent manner compared to the control group. In MCF-7 cells, TAC (p<0.05; p<0.01), Bax/Bcl-2 (p<0.001; p<0.0001) and Bax-Bcl-xl (p<0.01) ratios increased at 24 h compared to the control group. In Caco-2 cells, TAC (p<0.001), Bax/Bcl-2 ratios increased at 48 h (p<0.05), while Bax-Bcl-xl ratios decreased (p<0.01; p<0.001) compared to the control group. ConclusionC. laurifolius leaf extracts emerge as a promising anticancer candidate, hindering cell proliferation and inducing apoptosis in colon and breast cancer cells. The classification of bioactive molecules may facilitate further clinical therapeutic interventions targeting colon and breast cancer.

Synthesis of Black Seed Oil-loaded-, Alginate-based, pH-sensitive Beads Using Electrospraying Technique.

Black seed oil (BSO), derived from the seeds of the Nigella sativa plant, has garnered attention for its potential anti-cancer properties, particularly in the context of colon cancer. Its active compound, thymoquinone, may help inhibit cancer cell growth and induce apoptosis in colon cancer cells. Additionally, black seed oil's anti-inflammatory and antioxidant effects could contribute to a healthier gut environment, potentially reducing cancer risk. Therefore, this study synthesized pH-sensitive alginate beads to deliver BSO into the colon in a controlled-release manner without releasing the drug at pH 1.2 (stomach), thus providing a well-defined release pattern at pH 6.8. The use of electrospray technology improves process performance by making it easier to formulate small, homogeneous beads with a higher rate of swelling and diffusion in the gastrointestinal medium. The formulated beads were characterized by an ex-vivo mucoadhesive strength test, bead size, sphericity factor (SF), encapsulation efficiency (EE), scanning electron microscope (SEM), in vitro swelling behavior (SB), and in vitro drug release in acidic and buffer media. All these manufactured beads demonstrated modest sizes of 0.58 ± 0.01 mm and spherical shape of 0.03 ± 0.00 mm in this testing. The formulation showed promising floating and releasing properties in vitro. With a very low cumulative percentage of beads, the oil EE of 90.13% ± 0.93% was high, and the release study demonstrated more than 90% in pH 6.8 with good floating nature in the stomach. Additionally, the beads were evenly spaced throughout the intestine. The electrospraying approach used in this protocol can be reproducible, yielding consistent outcomes. Therefore, this protocol can be used for large-scale production for commercialization purposes.

Antibacterial Peptide Nisin Activates p53 Gene Expression and Triggers Apoptosis in Human Colon Cancer Cells

ABSTRACTAntimicrobial peptides (AMPs) are renowned for their broad‐spectrum efficacy against viruses, bacteria, and fungi, thereby holding promise for medicinal applications. Nisin, a bacteriocin synthesized by gram‐positive bacteria such as Lactobacillus and Streptococcus, has been used as a food preservative owing to its antimicrobial characteristics for decades. However, recent developments prompt further research on its application as therapeutic interventions, mainly focusing on anticancer activity. In line with this, the present study portrays the effects of nisin on human colorectal cancer cells and the underlying molecular mechanisms. A dose‐dependent decrease in cell viability with increasing concentrations of nisin was determined by the Alamar blue viability assay, which was supported by significant morphological changes in cells. Subsequently, we probed the apoptotic effects of nisin using EtBr/AO staining, confirming the induction of apoptosis upon nisin treatment, which was further confirmed by ELISA analysis. Elevated levels of Caspase 7 indicated increased apoptosis in nisin‐treated cells. As pharmaceutical p53 reactivation is considered as an attractive strategy to combat chemoresistance and adverse effects, the effect of nisin on p53 expression was determined by mRNA analysis. An upregulation in p53 expression in nisin‐treated cells compared to untreated controls suggests that bacterial nisin reactivates mutated p53. To assess cell cycle dynamics, we utilized PI flow cytometry, unveiling a G0/G1 phase arrest in nisin‐treated cells in contrast to untreated controls. In summary, our results strongly advocate the potential of nisin as a compelling candidate for drug development against colorectal cancer.

Kaempferol Synergistically Enhances Cisplatin-induced Apoptosis and Cell Cycle Arrest in Colon Cancer Cells.

Colon cancer remains a significant global health concern, necessitating the continuous exploration of novel therapeutic strategies. Cisplatin is a first-line chemotherapy medication that is frequently used to treat patients for a variety of malignancies, including colon cancer. However, a major obstacle to its clinical usefulness is acquired resistance. This research investigates the synergistic effects of kaempferol, a natural flavonoid with known anti-cancer properties, in combination with cisplatin, in colon cancer cells. Our study employed colon cancer cell lines to evaluate the individual and combined cytotoxic effects of kaempferol and cisplatin. The results demonstrated a notable enhancement in the cytotoxicity of colon cancer cells when treated with a combination of kaempferol and cisplatin compared to individual treatments. This synergistic effect was further characterized by an increase in apoptosis, as evidenced by morphological changes and biochemical markers of apoptosis and cell cycle. The investigations revealed that the combined treatment led to the modulation of key apoptotic pathways, including the upregulation of pro-apoptotic factors and downregulation of anti-apoptotic factors. Additionally, the synergistic effect was associated with the inhibition of cell proliferation and induction of cell cycle arrest. The findings of this study suggest that the combination of kaempferol and cisplatin holds promise as a potent therapeutic strategy for colon cancer treatment, potentially enhancing the efficacy of conventional chemotherapy while minimizing adverse effects. Further in-depth investigations, including in vivo studies, are warranted to validate these findings and explore the translational potential of this synergistic approach in clinical settings.

A New Combination of Bifidobacterium bifidum and Lactococcus lactis Strains with Synergistic Effects Alleviates Colitis-Associated Colorectal Cancer.

Chronic inflammation is a factor in the development of cancer, and probiotics play a role in preventing or treating inflammation as an adjuvant therapy. To investigate potential probiotics for the prevention of colitis-associated colorectal cancer (CAC), Bifidobacterium bifidum H3-R2 and Lactococcus lactis KLDS4.0325 were used to examine the effects on colon cancer cells and in an inflammation-related cancer animal model. The results revealed that B. bifidum H3-R2 in combination with L. lactis KLDS4.0325 caused apoptosis in colon cancer cells by increasing caspase-3 and caspase-9 protein levels, enhancing Bax expression, and lowering Bcl-2 expression. In addition, the combination of the two strains relieved the tissue damage; reduced proinflammatory cytokines, myeloperoxidase (MPO) activity, and hypoxia-inducible factor 1-alpha (HIF-1α) level; upregulated anti-inflammatory cytokines; increased colonic tight junction protein expression; regulated intestinal homeostasis by inhibiting NLRP3 inflammasome signaling pathway; and improved the imbalance of gut microbiota in animal models. Moreover, the combination of the two strains had a greater preventive impact than each strain alone. These findings are supportive of clinical studies and product development of multi-strain probiotic preparations for diseases associated with colitis.

Inhibition of hERG by ESEE suppresses the progression of colorectal cancer

Colorectal cancer (CRC) is one of the most common malignant cancers. Emodin is a lipophilic anthraquinone commonly found in medicinal herbs and known for its antitumor properties. However, its clinical utility has been hampered by low druggability. We designed and synthesized a new compound named Emodin succinimidyl ethyl ester (ESEE), which improves the bioavailability and preserves the original pharmacological effects of Emodin. In vitro, we have confirmed that ESEE induces apoptosis in colon cancer cells, suppresses cell proliferation, migration, and invasion, and inhibits the growth of subcutaneous transplantation tumors associated with colon cancer. And, in vivo, ESEE robustly inhibited tumor growth. Human Ether-a-go-go Related Gene (hERG) is aberrantly expressed in various cancer cells, where they play an important role in cancer progression. Focal adhesion kinase (FAK) is a tyrosine kinase overexpressed in cancer cells and plays an important role in the progression of tumors to a malignant phenotype. Mechanistically, the anti-CRC properties of ESEE are exerted through direct binding with hERG, which impedes the FAK/PI3K/AKT signaling axis-dependent apoptotic cascade.

Copper(I) Complexes With Phenanthroline‐Functionalized NHC Ligands Achieve Effective Anticancer Activity via Mitochondrial and Endoplasmic Reticulum Stress

ABSTRACTCopper complexes exhibit promising anticancer properties, which can be further promoted by suitable ligands. In this study, we synthesized and investigated the anticancer effects of three copper(I) complexes with N‐heterocyclic carbene (NHC) ligands derived from phenanthroline‐functionalized imidazole salts. The synthesis of these NHC‐copper(I) complexes (Cu1‐Cu3) was meticulously characterized using NMR and elemental analysis; their crystal structures were further delineated by X‐ray diffraction. Our findings illustrate the unique geometric configurations of these complexes: Cu1 features a dinuclear arrangement with off‐linear geometry; Cu2 and Cu3 are characterized by a bi‐copper core stabilized by two phenanthroline‐modified carbene ligands. Crucially, in vitro cytotoxic evaluations revealed that these complexes possess suitability anticancer activity. Among them, Cu2 exhibited enhanced cytotoxicity activity, achieving a half‐maximal inhibitory concentration (IC50) of 4.36 ± 0.25 μM in colon cancer cell line HCT‐116, markedly surpassing the efficacy of cisplatin. Subsequent investigations elucidated that Cu2 notably increases intracellular reactive oxygen species (ROS) levels and induces mitochondrial membrane depolarization and endoplasmic reticulum stress, leading to oxidative stress‐mediated apoptosis of colon cancer cells.

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.

A comprehensive view on the fisetin impact on colorectal cancer in animal models: Focusing on cellular and molecular mechanisms.

Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, and transcription factors. The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of murine double minute 2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI and cytochrome c. Furthermore, fisetin inhibits the cyclooxygenase-2 and wingless-related integration site (Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4, reducing retinoblastoma protein phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2 promoter binding factor 1 and cell division cycle 2 (CDC2) protein levels. Additionally, fisetin exhibits various effects on CRC cells, including inhibiting the phosphorylation of Y-box binding protein 1 and ribosomal S6 kinase, promoting the phosphorylation of extracellular signal-regulated kinase 1/2, and disrupting the repair process of DNA double-strand breaks. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA)-mutant CRC, resulting in a reduction in phosphatidylinositol-3 kinase (PI3K) expression, Ak strain transforming phosphorylation, mTOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation. These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.

RETRACTION: SLC1A3 Promotes Gastric Cancer Progression via the PI3K/AKT Signalling Pathway.

Xu L, Chen J, Jia L, Chen X, Moumin FA, Cai J. SLC1A3 Promotes Gastric Cancer Progression via the PI3K/AKT Signalling Pathway. Journal of Cellular and Molecular Medicine 2020;24(24):14392-14404. https://doi.org/10.1111/jcmm.16060 The above article, published online on 3 November 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stefan N. Constantinescu; the Foundation for Cellular and Molecular Medicine; and John Wiley & Sons Ltd. The retraction has been agreed due to concerns raised by third parties. Specifically, image elements of Figure6G were found to have been previously published in a different scientific context.1 The corresponding author stated that a third-party company partially generated the data presented in the article and suggested there may have been mishandling of the data. Additionally, the article mentions use of the unverifiable/unknown cell line GSE-1 and presents results from the cell line MKN-28, reported as misidentified by the Japanese Collection of Research Bioresources (JCRB) Cell Bank of the National Institutes of Biomedical Innovation, Health and Nutrition (https://cellbank.nibiohn.go.jp/). Therefore, the editors consider the conclusions of this article to be invalid. The authors have been informed of the decision of retraction. [1] Pang X, Li R, Shi D, Pan X, Ma C, Zhang G, Mu C, Chen W. Knockdown of Rhotekin 2 expression suppresses proliferation and induces apoptosis in colon cancer cells. Oncol Lett. 2017;14(6):8028-8034. https://doi.org/10.1111/jcmm.16060.

Effect of Pterostilbene Regulating Nuclear Factor E2-Related Factor 2 on Apoptosis of Colon Cancer Cells in Vitro

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2 (Nrf2) in the process of pterostilbene acting on LoVo cells. Methods LoVo cells were treated with different concentrations (5,10,20,40,60,80,100 μmol/L) of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Transwell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochondrial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlorofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic proteins (Bcl2 and Bax) were determined by Western blotting.In addition,cell viability,Nrf2 expression,and apoptosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane. Results Compared with the control group,40,60,80,100 μmol/L pterostilbene reduced the viability of LoVo cells (P=0.014,P<0.001,P<0.001,P<0.001).Pterostilbene at 5,10,20 μmol/L did not show effects on cell viability but inhibited cell migration (P=0.008,P<0.001,P<0.001) and invasion (all P<0.001).Pterostilbene at 40,60,80 μmol/L increased apoptosis (P=0.014,P<0.001,P<0.001),promoted mitochondrial membrane potential depolarization (P=0.026,P<0.001,P<0.001) and reactive oxygen species accumulation (all P<0.001),and down-regulated the expression of phosphorylated Nrf2 (P=0.030,P<0.001,P<0.001),heme oxygenase 1 (P=0.015,P<0.001,P<0.001),and Bcl2 (P=0.039,P<0.001,P<0.001) in LoVo cells.Pterostilbene at 60,80 μmol/L down-regulated Nrf2 expression (P=0.001,P<0.001) and up-regulated Bax expression (both P<0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability (P<0.001),apoptosis (P<0.001),and Nrf2 expression (P=0.022). Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Superparamagnetic Fe3O4 nanoparticles capped with silver induce apoptosis of colon cancer cells via damaging DNA@increasing ROS

A sol-gel approach was used to create magnetite nanoparticles (Fe3O4 NPs) as a core and silver (Ag) as a shell. Ag-Fe3O4 NPs were identified by x-ray diffraction (XRD) and energy dispersive x-ray (EDX), scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, and vibrating sample magnetometer (VSM) techniques. The capabilities of Ag-Fe3O4 NPs to induce apoptosis were investigated utilizing the Acridine orange/Ethidium bromide stain. The activity of NPs against (HT-29) cancer cells was further evaluated in and out of the existence of near-infrared (NIR) laser beam and alternating magnetic field (AMF). The exposed laser enhanced the cytotoxicity effect against (HT-29) cells. However, greatly elevated cytotoxic activity was seen with using the AMF.

Harmine inhibits the proliferation and migration and promotes the apoptosis of colon cancer cells via inhibition of the FAK/AKT and ERK1/2/CREB signaling pathways

Harmine is present in a variety of medicinal plants, and its effects on colon cancer cells remain unclear. Here, we found that harmine exhibited significant inhibitory effects on the proliferation of colon cancer cells by inhibiting the phosphorylation levels of the FAK/AKT and ERK1/2/CREB. Furthermore, harmine also inhibited the migration of colon cancer cells and suppressed the expression levels of MMP-2, MMP-9, and VEGF. Additionally, harmine-induced apoptosis in colon cancer cells by regulating the expression of Bcl-2 and Bax. In conclusion, our findings suggest that harmine exerts a significant inhibitory effect on the development of colon cancer cells.

Sm-like 5 knockdown inhibits proliferation and promotes apoptosis of colon cancer cells by upregulating p53, CDKN1A and TNFRSF10B.

The role of Sm-like 5 (LSM5) in colon cancer has not been determined. In this study, we investigated the role of LSM5 in progression of colon cancer and the potential underlying mechanism involved. To determine the role of LSM5 in the progression of colon cancer and the potential underlying mechanism involved. The Gene Expression Profiling Interactive Analysis database and the Human Protein Atlas website were used for LSM5 expression analysis and prognosis analysis. Real-time quantitative polymerase chain reaction and Western blotting were utilized to detect the expression of mRNAs and proteins. A lentivirus targeting LSM5 was constructed and transfected into colon cancer cells to silence LSM5 expression. Proliferation and apoptosis assays were also conducted to evaluate the growth of the colon cancer cells. Human GeneChip assay and bioinformatics analysis were performed to identify the potential underlying mechanism of LSM5 in colon cancer. LSM5 was highly expressed in tumor tissue and colon cancer cells. A high expression level of LSM5 was related to poor prognosis in patients with colon cancer. Knockdown of LSM5 suppressed proliferation and promoted apoptosis in colon cancer cells. Silencing of LSM5 also facilitates the expression of p53, cyclin-dependent kinase inhibitor 1A (CDKN1A) and tumor necrosis factor receptor superfamily 10B (TNFRSF10B). The inhibitory effect of LSM5 knockdown on the growth of colon cancer cells was associated with the upregulation of p53, CDKN1A and TNFRSF10B. LSM5 knockdown inhibited the proliferation and facilitated the apoptosis of colon cancer cells by upregulating p53, CDKN1A and TNFRSF10B.

Caffeic Acid Enhances Anticancer Drug-induced Apoptosis in Acid-adapted HCT116 Colon Cancer Cells.

Apoptosis resistance in cancer cells adapted to acidic microenvironments poses a challenge for effective treatment. This study investigated the potential use of caffeic acid as an adjunct therapy to overcome drug resistance in colorectal cancer cells under acidic conditions. Long-term exposure to low-pH conditions induced resistance in HCT116 colorectal cancer cells. The effects of caffeic acid on proliferation, clonogenicity, and apoptosis induction were assessed alone and in combination with oxaliplatin and 5-Fluorouracil. The signaling pathways involved in drug resistance were examined by assessing the activities of PI3K/Akt and ERK1/2. Caffeic acid inhibited the proliferation and clonogenicity of acid-adapted cancer cells, and enhanced apoptosis when combined with anticancer drugs. Mechanistically, caffeic acid attenuated the hyperactivation of the PI3K/Akt and ERK1/2 signaling pathways associated with drug resistance. Caffeic acid is a promising therapeutic agent for targeting resistant cancer cells in acidic microenvironments. Its ability to inhibit proliferation, sensitize cells to apoptosis, and modulate signaling pathways highlights its potential for overcoming drug resistance in cancer therapy.

Negative regulation of HDAC3 transcription by histone acetyltransferase TIP60 in colon cancer

BackgroundColon cancer is the third most common cancer globally. The expression of histone deacetylase 3 (HDAC3) is upregulated, whereas the expression of tat interactive protein, 60 kDa (TIP60) is downregulated in colon cancer. However, the relationship between HDAC3 and TIP60 in colon cancer has not been clearly elucidated.ObjectiveWe investigated whether TIP60 could regulate the expression of HDAC3 and suppress colon cancer cell proliferation.MethodsRNA sequencing data (GSE108834) showed that HDAC3 expression was regulated by TIP60. Subsequently, we generated TIP60-knockdown HCT116 cells and examined the expression of HDAC3 by western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We examined the expression pattern of HDAC3 in various cancers using publicly available datasets. The promoter activity of HDAC3 was validated using a dual-luciferase assay, and transcription factors binding to HDAC3 were identified using GeneCards and Promo databases, followed by validation using chromatin immunoprecipitation-quantitative polymerase chain reaction. Cell proliferation and apoptosis were assessed using colony formation assays and fluorescence-activated cell sorting analysis of HCT116 cell lines.ResultsIn response to TIP60 knockdown, the expression level and promoter activity of HDAC3 increased. Conversely, when HDAC3 was downregulated by overexpression of TIP60, proliferation of HCT116 cells was inhibited and apoptosis was promoted.ConclusionTIP60 plays a crucial role in the regulation of HDAC3 transcription, thereby influencing cell proliferation and apoptosis in colon cancer. Consequently, TIP60 may function as a tumor suppressor by inhibiting HDAC3 expression in colon cancer cells.

The anticancer impact of folate-linked ZnO-decorated bovine serum albumin/silibinin nanoparticles on human pancreatic, breast, lung, and colon cancers

In the current study, we aimed to design an individual hybrid silibinin nano-delivery system consisting of ZnO and BSA components to study its antioxidant activity and apoptotic potential on human pancreatic, breast, lung, and colon cancer cell lines. The folate-linked ZnO-decorated bovine serum albumin/silibinin nanoparticles (FZBS-NP) were synthesized and characterized by FTIR, FESEM, DLS, and zeta potential analysis. The FZBS-NP’s cytotoxicity was evaluated by measuring the cancer cells’ (MCF-7, A549, HT-29, and Panc) viability. Moreover, the apoptotic potential of the nanoparticles was studied by conducting several analyses including AO/PI and DAPI cell staining analysis, apoptotic gene expression profile (BAX, BCL2, and Caspase-8) preparation, and FITC Annexin V/PI flow cytometry. Finally, both antioxidant assays (ABTS and DPPH) were utilized to analyze the FZBS-NPs’ antioxidant activities. The 152-nm FZBS-NP significantly induced the selective apoptotic death on the MCF-7, A549, HT-29, Panc, and Huvec cancer cells by increasing the SubG1 cell population following the increased treatment concentrations of FZBS-NP. Moreover, the FZBS-NPs exhibited powerful antioxidant activity. The BSA component of the FZBS-NPs delivery system improves the ability of the nanoparticles to gradually release silibinin and ZnO near the cancer cells. On the other hand, considering the powerful antioxidant activity of FZBS-NP, they have the potential to selectively induce apoptosis in human colon and breast cancer cells and protect normal types, which makes it an efficient safe anticancer compound. However, to verify the FZBS-NP anti-cancer efficiency further cancer and normal cell lines are required to measure several types of apoptotic gene expression.

SP1-induced circ_0017552 modulates colon cancer cell proliferation and apoptosis via up-regulation of NET1

Colon cancer (CC) is a common malignancy over the world and its morbidity and mortality significantly went up in China in recent years. Molecular functions in cancers have gradually been the pivot subject in cancer research. Neuroepithelial cell transforming 1 (NET1) was reported to contribute to prostate cancer and gastric cancer. Our study figured out that NET1 was overexpressed in CC cells. Then, loss-of-function assays revealed that NET1 facilitated CC cell proliferation and repressed CC cell apoptosis. Next, miR-338–3p was confirmed to target NET1. After that, we verified that circ_0017552 which originates from NET1 could positively modulate NET1 expression. Besides, circ_0017552 was a sponge of miR-338–3p. Rescue assays’ results demonstrated that circ_0017552 could regulate CC cell proliferation and apoptosis through up-regulation of NET1. A transcription factor named Sp1 (SP1) was found to be present in circ_0017552. SP1 induced transcription of circ_0017552 to facilitate CC cell proliferation and inhibit CC cell apoptosis. In a word, SP1-induced circ_0017552 regulated CC cell proliferation and apoptosis through miR-338–3p/NET1 axis.

Macromolecules with predominant β-pleated sheet proteins in extracellular vesicles released from Raphanus sativus L. var. caudatus Alef microgreens induce DNA damage-mediated apoptosis in HCT116 colon cancer cells

Plant-derived bioactive macromolecules (i.e., proteins, lipids, and nucleic acids) were prepared as extracellular vesicles (EVs). Plant-derived EVs are gaining pharmaceutical research interest because of their bioactive components and delivery properties. The spherical nanosized EVs derived from Raphanus sativus L. var. caudatus Alef microgreens previously showed antiproliferative activity in HCT116 colon cancer cells from macromolecular compositions (predominantly proteins). To understand the mechanism of action, the biological activity studies, i.e., antiproliferation, cellular biochemical changes, DNA conformational changes, DNA damage, apoptotic nuclear morphological changes, apoptosis induction, and apoptotic pathways, were determined by neutral red uptake assay, synchrotron radiation-based Fourier transform infrared microspectroscopy, circular dichroism spectroscopy, comet assay, 4′,6-diamidino-2-phenylindole (DAPI) staining, flow cytometry, and caspase activity assay, respectively. EVs inhibited HCT116 cell growth in concentration- and time-dependent manners, with a half-maximal inhibitory concentration of 675.4 ± 33.8 μg/ml at 48 h and a selectivity index of 1.5 ± 0.076. HCT116 treated with EVs mainly changed the cellular biochemical compositions in the nucleic acids and carbohydrates region. The DNA damage caused no changes in DNA conformation. The apoptotic nuclear morphological changes were associated with the increased apoptotic cell population. The apoptotic cell death was induced by both extrinsic and intrinsic pathways. EVs have potential as antiproliferative bioparticles.

Retraction: MiR-34b inhibits the proliferation and promotes apoptosis in colon cancer cells by targeting Wnt/β-catenin signaling pathway.

Retraction: MiR-34b inhibits the proliferation and promotes apoptosis in colon cancer cells by targeting Wnt/β-catenin signaling pathway.