Biological activities of siRNA-loaded lanthanum phosphate nanoparticles on colorectal cancer

Colorectal cancer (CRC) is one of the most common malignancies and most frequent cause of cancer death worldwide. The activation of both NF-κB and STAT3 signaling and the crosstalk between them play an important role in colorectal tumor.Helicteres angustifoliaL. is a type of commonly used Chinese medicinal herb and possesses a wide variety of biological activities. In the present study, we investigate the effects of three triterpenes fromH. angustifolia(HT) such as helicteric acid (HA), oleanic acid (OA), and betulinic acid (BA), on inhibiting CRC progression. Our results showed that HT extracts could decrease proliferation and induce apoptosis in HT-29 colorectal cancer cells. Moreover, HT extracts could suppress LPS-triggered phosphorylation of IKK, IκB, and NF-κB, attenuate IL-6-induced phosphorylation of JAK2 and STAT3, and suppress the expression of c-Myc, cyclin-D1, and BCL-xL, the downstream gene targets of NF-κB and STAT3. Therefore, HT extracts showed potent therapeutic and antitumor effects on CRC via inhibiting NF-κB and STAT3 signaling.

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Long non-coding RNA RP11-468E2.5 curtails colorectal cancer cell proliferation and stimulates apoptosis via the JAK/STAT signaling pathway by targeting STAT5 and STAT6

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1428-0 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 10

Author(s):

Li Jiang ◽

Xu-Hai Zhao ◽

Yin-Ling Mao ◽

Jun-Feng Wang ◽

Hui-Jun Zheng ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Target Genes ◽

Biological Activities ◽

Janus Kinase ◽

Normal Tissues ◽

Stat Signaling

Abstract Background Long non-coding RNAs (lncRNAs) are tumor-associated biological molecules and have been found to be implicated in the progression of colorectal cancer (CRC). This study aims to examine the effects of lncRNA RP11-468E2.5 and its target genes (STAT5 and STAT6) on the biological activities of CRC cells via the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway. Methods We initially screened the GEO database for differentially expressed lncRNAs related to CRC and then made a prediction of the implicated target genes. Then we collected CRC tissues and adjacent normal tissues from 169 CRC patients. Human CRC HCT116 and SW480 cells were treated with small interference RNA (siRNA) against RP11-468E2.5, AG490 (an inhibitor of the JAK/STAT signaling pathway), or both in combination. Next, we measured the effects of RP11-468E2.5 treatment on cellular activities such as cell viability, cycle distribution and cell apoptosis, and studied interactions among RP11-468E2.5, STAT5/STAT6, and the JAK/STAT signaling pathway. Finally, an in vivo tumor formation assay was performed to observe the effect of RP11-468E2.5 on tumor growth. Results The CRC-related gene microarray data showed low expression of RP11-468E2.5 in CRC surgical specimens. However, RP11-468E2.5 was confirmed to target STAT5 and STAT6, which participate in the JAK/STAT signaling pathway. CRC tissues showed lower expression of RP11-468E2.5, higher expression of STAT5, STAT6 and of the cell cycle marker Cyclin D1 (CCND1), compared to the findings in adjacent normal tissues. The treatment of siRNA against RP11-468E2.5 increased expression of JAK2, STAT3, STAT5, STAT6, CCND1 and Bcl-2 along with the extent of STAT3, STAT5 and STAT6 phosphorylation, while lowering expression of P21 and P27. Treatment with AG490 exhibited approximately opposite effects, whereas siRNA against RP11-468E2.5 treatment stimulated CRC cell proliferation and reduced cell apoptosis, while promoting cell cycle entry; AG490 treatment reversed these results. Conclusions Altogether, we conclude that up-regulation of RP11-468E2.5 inhibits the JAK/STAT signaling pathway by targeting STAT5 and STAT6, thereby suppressing cell proliferation and promoting cell apoptosis in CRC.

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Anticancer Activity of 2-O-caffeoyl Alphitolic Acid Extracted from the Lichen, Usnea barbata 2017-KL-10

Molecules ◽

10.3390/molecules26133937 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3937

Author(s):

Hae-Jung Chae ◽

Geum-Jin Kim ◽

Barsha Deshar ◽

Hyun-Jin Kim ◽

Min-Ji Shin ◽

...

Keyword(s):

Colorectal Cancer ◽

Biological Activities ◽

Biological Effects ◽

Cancer Cell Line ◽

Colorectal Cancer Cell Line ◽

Migration And Invasion ◽

Dependent Manner ◽

Anticancer Activities ◽

Concentration Dependent Manner ◽

Mortality And Morbidity

Colorectal cancer is one of the life-threatening ailments causing high mortality and morbidity worldwide. Despite the innovation in medical genetics, the prognosis for metastatic colorectal cancer in patients remains unsatisfactory. Recently, lichens have attracted the attention of researchers in the search for targets to fight against cancer. Lichens are considered mines of thousands of metabolites. Researchers have reported that lichen-derived metabolites demonstrated biological effects, such as anticancer, antiviral, anti-inflammatory, antibacterial, analgesic, antipyretic, antiproliferative, and cytotoxic, on various cell lines. However, the exploration of the biological activities of lichens’ metabolites is limited. Thus, the main objective of our study was to evaluate the anticancer effect of secondary metabolites isolated from lichen (Usnea barbata 2017-KL-10) on the human colorectal cancer cell line HCT116. In this study, 2OCAA exhibited concentration-dependent anticancer activities by suppressing antiapoptotic genes, such as MCL-1, and inducing apoptotic genes, such as BAX, TP53, and CDKN1A(p21). Moreover, 2OCAA inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that 2OCAA is a better therapeutic candidate for colorectal cancer.

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Molecular genetic evaluation of Cichorium endivia L. as an anticancer agent against colorectal cancer

International Journal of Phytomedicine ◽

10.5138/09750185.1916 ◽

2017 ◽

Vol 8 (4) ◽

pp. 551 ◽

Cited By ~ 3

Author(s):

Elsayed E Hafez ◽

Effat Badr ◽

Yasser Mabrouk ◽

Mohammed El-Seehy ◽

Sarah Aggag

Keyword(s):

Colorectal Cancer ◽

Body Weight ◽

Biological Activities ◽

Molecular Genetic ◽

Antioxidant Compounds ◽

Protective Effects ◽

Differential Display Pcr ◽

Wide Range ◽

Cichorium Endivia ◽

Different Doses

Medicinal plants confer protective effects against a wide range of cancers including colon cancer. Cichorium endivia L. has many biological activities and functions, such as anti-inflammation and hepatoprotective effects. This activity is mainly due to its high levels of antioxidant compounds. The effect of cichorium extract and fluorouracil (5-FU) against colorectal cancer (CRC) induced by 1, 2- Dimethyl hydrazine (DMH) was examined in male albino mice. Where, different doses of cichorium extract (200, 400 and 600 mg/kg body weight) were investigated to determine the significant effective dose against colorectal cancer using differential display-PCR (DD-PCR), DNA sequencing, histopathological and cytological techniques. The results showed that the cichorium extract dose 200 mg/kg body weight was the best one compared to the others (400 and 600 mg/kg body weight). This finding could be a powerful therapeutic against colorectal cancer.

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Saponin-Rich Extracts and Their Acid Hydrolysates Differentially Target Colorectal Cancer Metabolism in the Frame of Precision Nutrition

Cancers ◽

10.3390/cancers12113399 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3399

Author(s):

Marta Gómez de Cedrón ◽

Joaquín Navarro del Hierro ◽

Marina Reguero ◽

Sonia Wagner ◽

Adrián Bouzas ◽

...

Keyword(s):

Colorectal Cancer ◽

Lipid Metabolism ◽

Molecular Mechanisms ◽

Cancer Metabolism ◽

Therapeutic Potential ◽

Biological Activities ◽

Aerobic Glycolysis ◽

Metabolic Reprogramming ◽

Specific Subgroup ◽

Bioactive Agents

Saponins or their aglycone form, sapogenin, have recently gained interest as bioactive agents due to their biological activities, their antitumoral effects being among them. Metabolic reprogramming has been recognized as a hallmark of cancer and, together with the increased aerobic glycolysis and glutaminolysis, the altered lipid metabolism is considered crucial to support cancer initiation and progression. The purpose of this study was to assess and compare the inhibitory effects on colorectal cancer cell lines of saponin-rich extracts from fenugreek and quinoa (FE and QE, respectively) and their hydrolyzed extracts as sapogenin-rich extracts (HFE and HQE, respectively). By mean of the latest technology in the analysis of cell bioenergetics, we demonstrate that FE and HFE diminished mitochondrial oxidative phosphorylation and aerobic glycolysis; meanwhile, quinoa extracts did not show relevant activities. Distinct molecular mechanisms were identified for fenugreek: FE inhibited the expression of TYMS1 and TK1, synergizing with the chemotherapeutic drug 5-fluorouracil (5-FU); meanwhile, HFE inhibited lipid metabolism targets, leading to diminished intracellular lipid content. The relevance of considering the coexisting compounds of the extracts or their hydrolysis transformation as innovative strategies to augment the therapeutic potential of the extracts, and the specific subgroup of patients where each extract would be more beneficial, are discussed in the frame of precision nutrition.

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Palladium Nanoparticles Functionalized with PVP-Quercetin Inhibits Cell Proliferation and Activates Apoptosis in Colorectal Cancer Cells

Applied Sciences ◽

10.3390/app11051988 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1988

Author(s):

Hilda Amelia Piñón-Castillo ◽

Rigoberto Martínez-Chamarro ◽

Reyna Reyes-Martínez ◽

Yarely M. Salinas-Vera ◽

Laura A. Manjarrez-Nevárez ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Catalytic Activity ◽

Cancer Cells ◽

Palladium Nanoparticles ◽

Biological Activities ◽

Chemical Reduction ◽

Significant Inhibition ◽

Colorectal Cancer Cells

Nanotechnology is focused on the development and application of novel nanomaterials with particular physicochemical properties. Palladium nanoparticles (PdNPs) have been used as antimicrobials, antifungals, and photochemicals and for catalytic activity in dye reduction. In the present investigation, we developed and characterized PdNPs as a carrier of quercetin and initiated a study of its effects in colorectal cancer cells. PdNPs were first functionalized with polyvinylpyrrolidone (PVP) and then coupled to quercetin (PdNPs-PVP-Q). Our results showed that quercetin was efficiently incorporated to PdNPs-PVP, as demonstrated using UV/Vis and FT-IR spectroscopy. Using transmission electron microscopy, we demonstrated a reduction in size from 3–14.47 nm of PdNPs alone to 1.8–7.4 nm of PdNPs-PVP and to 2.12–3.14 of PdNPs-PVP-Q, indicating an increase in superficial area in functionalized PdNPs-Q. Moreover, hydrodynamic size studies using dynamic light scattering showed a reduction in size from 2120.33 nm ± 112.53 with PdNPs alone to 129.96 nm ± 6.23 for PdNPs-PVP-Q, suggesting a major reactivity when quercetin is coupled to nanoparticles. X-ray diffraction assays show that the addition of PVP or quercetin to PdNPs does not influence the crystallinity state. Catalytic activity assays of PdNPs-PVP-Q evidenced the chemical reduction of 4-nitrophenol, methyl orange, and methyl blue, thus confirming an electron acceptor capacity of nanoparticles. Finally, biological activity studies using MTT assays showed a significant inhibition (p < 0.05) of cell proliferation of HCT-15 colorectal cancer cells exposed to PdNPs-PVP-Q in comparison to untreated cells. Moreover, treatment with PdNPs-PVP-Q resulted in the apoptosis activation of HCT-15 cells. In conclusion, here we show for the first time the development of PdNPs-PVP-Q and evidence its biological activities through the inhibition of cell proliferation and apoptosis activation in colorectal cancer cells in vitro.

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ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2018.10.052 ◽

2019 ◽

Vol 161 ◽

pp. 456-467 ◽

Cited By ~ 1

Author(s):

Satya Narayan ◽

Srinivasa Ramisetti ◽

Aruna S. Jaiswal ◽

Brian K. Law ◽

Ashona Singh-Pillay ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Anticancer Agent ◽

Biological Activities

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Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients

Journal of Translational Medicine ◽

10.1186/s12967-021-02939-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Wei Zhang ◽

Liewen Lin ◽

Ligang Xia ◽

Wanxia Cai ◽

Weier Dai ◽

...

Keyword(s):

Colorectal Cancer ◽

Biological Activities ◽

Predictive Biomarkers ◽

Chromatin Accessibility ◽

Mitochondrial Genes ◽

Vital Role ◽

Mechanism Study ◽

Protein Levels ◽

Risk Patients ◽

Poor Outcomes

Abstract Background The identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment. However, no prognostic biomarker has been applied for colorectal cancer (CRC) in the clinic. Methods Integrated with transcriptomic data from public databases, multi-omics examinations were conducted to search prognostic biomarkers for CRC. Moreover, the potential biological functions and regulatory mechanism of these predictive genes were also explored. Results In this study, we revealed that three mitochondrial genes were associated with the poor prognosis of CRC. Integrated analyses of transcriptome and proteome of CRC patients disclosed numerous down-regulated mitochondrial genes at both mRNA and protein levels, suggesting a vital role of mitochondria in carcinogenesis. Combined with the bioinformatics studies of transcriptomic datasets of 538 CRC patients, three mitochondrial prognostic genes were eventually selected out, including HIGD1A, SUCLG2, and SLC25A24. The expression of HIGD1A exhibited a significant reduction in two subtypes of adenoma and six subtypes of CRC, while the down-regulation of SUCLG2 and SLC25A24 showed more advantages in rectal mucinous adenocarcinoma. Moreover, we unveiled that these three genes had common expressions and might collaboratively participate in the synthesis of ribosomes. Our original multi-omics datasets, including DNA methylation, structural variants, chromatin accessibility, and phosphoproteome, further depicted the altered modifications on their potential transcriptional factors. Conclusions In summary, HIGD1A, SUCLG2, and SLC25A24 might serve as predictive biomarkers for CRC. The biological activities they involved in and their upstream regulators we uncovered would provide a functional context for the further-in-depth mechanism study. Graphic abstract

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Polyphenols in Colorectal Cancer: Current State of Knowledge including Clinical Trials and Molecular Mechanism of Action

BioMed Research International ◽

10.1155/2018/4154185 ◽

2018 ◽

Vol 2018 ◽

pp. 1-29 ◽

Cited By ~ 42

Author(s):

Md Nur Alam ◽

Muhammad Almoyad ◽

Fazlul Huq

Keyword(s):

Colorectal Cancer ◽

Clinical Trials ◽

Molecular Mechanisms ◽

Biological Activities ◽

Wide Spectrum ◽

Future Directions ◽

Mortality And Morbidity ◽

Beneficial Effects ◽

Current State ◽

Molecular Mechanism Of Action

Polyphenols have been reported to have wide spectrum of biological activities including major impact on initiation, promotion, and progression of cancer by modulating different signalling pathways. Colorectal cancer is the second most major cause of mortality and morbidity among females and the third among males. The objective of this review is to describe the activity of a variety of polyphenols in colorectal cancer in clinical trials, preclinical studies, and primary research. The molecular mechanisms of major polyphenols related to their beneficial effects on colorectal cancer are also addressed. Synthetic modifications and other future directions towards exploiting of natural polyphenols against colorectal cancer are discussed in the last section.

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