Bioinspired silk fibroin nano-delivery systems protect against 5-FU induced gastrointestinal mucositis in a mouse model and display antitumor effects on HT-29 colorectal cancer cells in vitro

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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Synthesis, CYP24A1-Dependent Metabolism and Antiproliferative Potential against Colorectal Cancer Cells of 1,25-Dihydroxyvitamin D2 Derivatives Modified at the Side Chain and the A-Ring

International Journal of Molecular Sciences ◽

10.3390/ijms21020642 ◽

2020 ◽

Vol 21 (2) ◽

pp. 642

Author(s):

Magdalena Milczarek ◽

Michał Chodyński ◽

Anita Pietraszek ◽

Martyna Stachowicz-Suhs ◽

Kaori Yasuda ◽

...

Keyword(s):

Colorectal Cancer ◽

Vitamin D ◽

Cancer Cells ◽

Biologically Active ◽

Side Chain ◽

Anticancer Properties ◽

Colorectal Cancer Cells ◽

Ht 29

Experimental data indicate that low-calcemic vitamin D derivatives (VDDs) exhibit anticancer properties, both in vitro and in vivo. In our search for a vitamin D analog as potential anticancer agent, we investigated the influence of chirality in the side chain of the derivatives of 1,25-dihydroxyergocalciferol (1,25D2) on their activities. In this study, we synthesized modified analogs at the side chain and the A-ring, which differed from one another in their absolute configuration at C-24, namely (24S)- and (24R)-1,25-dihydroxy-19-nor-20a-homo-ergocalciferols (PRI-5105 and PRI-5106, respectively), and evaluated their activity. Unexpectedly, despite introducing double-point modifications, both analogs served as very good substrates for the vitamin D-hydroxylating enzyme. Irrespective of their absolute C-24 configuration, PRI-5105 and PRI-5106 showed relatively low resistance to CYP24A1-dependent metabolic deactivation. Additionally, both VDDs revealed a similar antiproliferative activity against HT-29 colorectal cancer cells which was higher than that of 1,25D3, the major biologically active metabolite of vitamin D. Furthermore, PRI-5105 and PRI-5106 significantly enhanced the cell growth-inhibitory activity of 5-fluorouracil on HT-29 cell line. In conclusion, although the two derivatives showed a relatively high anticancer potential, they exhibited undesired high metabolic conversion.

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1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane potentiates in vitro and in vivo antitumor effects of irinotecan on human colorectal cancer cells

Oncology Letters ◽

10.3892/ol.2016.4430 ◽

2016 ◽

Vol 11 (5) ◽

pp. 3551-3557

Author(s):

PO-SHENG YANG ◽

JANE-JEN WANG ◽

YEA-HWEY WANG ◽

WOAN-CHING JAN ◽

SHIH-PING CHENG ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Human Colorectal Cancer ◽

Antitumor Effects ◽

Colorectal Cancer Cells ◽

Human Colorectal Cancer Cells

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IL-24-armed oncolytic vaccinia virus exerts potent antitumor effects via multiple pathways in colorectal cancer

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504020x15942028641011 ◽

2020 ◽

Author(s):

Lili Deng ◽

Xue Yang ◽

Jun Fan ◽

Yuedi Ding ◽

Ying Peng ◽

...

Keyword(s):

Colorectal Cancer ◽

Vaccinia Virus ◽

Cancer Cells ◽

Treatment Options ◽

Antitumor Effects ◽

Colorectal Cancer Cells ◽

Cancer Tumor ◽

Induced Apoptosis

Colorectal cancer is an aggressive malignancy for which there are limited treatment options. Oncolytic vaccinia virus isbeing developed as a novel strategy for cancer therapy. Arming vaccinia virus with immunostimulatory cytokines can enhance the tumor cell-specific replication and antitumor efficacy. Interleukin-24 (IL-24) is an important immune mediator, as well as a broad-spectrum tumor suppressor. Here, we constructed a targeted vaccinia virus of Guang9 strain harbored IL-24 (VG9-IL-24) to evaluate its antitumor effects. In vitro, VG9-IL-24 induced increased number of apoptotic cells and blocked colorectal cancer cells in the G2/M phase of the cell cycle. VG9-IL-24 induced apoptosis in colorectal cancer cells via multiple apoptotic signaling pathways. In vivo,VG9-IL-24 significantly inhibited the tumor growth and prolonged the survival both in human and murine colorectal cancer models. Besides, VG9-IL-24 stimulated multiple antitumor immune responses and direct bystander antitumor activity. Our results indicate that VG9-IL-24 can inhibit the growth of colorectal cancer tumor by inducing oncolysis and apoptosis as well as stimulating the anti-tumor immune effects. These findings indicate that VG9-IL-24 may exert a potential therapeutic strategy for combating colorectal cancer

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Inhibitory effect of VEGF antisense oligonucleotide on HT-29 human colorectal cancer cells in vitro

World Chinese Journal of Digestology ◽

10.11569/wcjd.v16.i25.2831 ◽

2008 ◽

Vol 16 (25) ◽

pp. 2831

Author(s):

De-Chuang Jiao ◽

Ai-Guo Wu ◽

Guo-Li Shao ◽

Shu-Feng Ji

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Antisense Oligonucleotide ◽

Inhibitory Effect ◽

Human Colorectal Cancer ◽

Colorectal Cancer Cells ◽

Ht 29 ◽

Human Colorectal Cancer Cells

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Inhibitory effect of selenomethionine on carcinogenesis in the model of human colorectal cancer in vitro and its link to the Wnt/β-catenin pathway.

Acta Biochimica Polonica ◽

10.18388/abp.2018_2628 ◽

2018 ◽

Vol 65 (3) ◽

Cited By ~ 2

Author(s):

Edyta Korbut ◽

Agata Ptak-Belowska ◽

Tomasz Brzozowski

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Colorectal Carcinogenesis ◽

Mrna Levels ◽

Human Colorectal Cancer ◽

Bax Protein ◽

Colorectal Cancer Cells ◽

Gsk 3Β ◽

Ht 29

Selenium compounds have been implicated as anticancer agents; however, the mechanism of their inhibitory action against cancer development has not been extensively investigated. The constitutive activation of the Wnt/β-catenin pathway is a central event in colorectal carcinogenesis. In this pathway, the excessive cell proliferation is initiated by the generation of β-catenin followed by overexpression of proto-oncogenes such as c-Myc. It is believed that under physiological conditions the level of c-Myc is efficiently controlled by accessibility of β-catenin protein through the process of phosphorylation by glycogen synthase kinase 3β (GSK-3β). Here, we determined whether selenomethionine (SeMet) can inhibit cell growth and affect the Wnt/β-catenin pathway in HT-29 human colorectal cancer cells in vitro. The effective cytotoxic doses of SeMet have been selected after 48 h of incubation of this compound with colorectal cancer HT-29 cell line. The MTT assay was used to assess cell viability and the protein and mRNA levels of β-catenin and c-Myc were determined by Western blotting and qPCR, respectively. The SeMet potently inhibited growth of HT-29 cells, significantly decreased the β-catenin protein and mRNA concentration, down-regulated the c-Myc gene expression and up-regulated pro-apoptotic Bax protein expression. Moreover, SeMet increased the level of GSK-3β phosphorylated at serine 9 (S9) and significantly increased the level of β-catenin phosphorylated at S33 and S37. We conclude that SeMet suppresses the growth of HT-29 colorectal cancer cells by the mechanism linked to the Wnt/β-catenin pathway, however, the degradation of β-catenin may occur independently of GSK-3β catalytic activity and its phosphorylation status.

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α-Linolenic and γ-linolenic acids exercise differential antitumor effects on HT-29 human colorectal cancer cells

Toxicology Research ◽

10.1093/toxres/tfaa046 ◽

2020 ◽

Vol 9 (4) ◽

pp. 474-483 ◽

Cited By ~ 1

Author(s):

María José González-Fernández ◽

Ignacio Ortea ◽

José Luis Guil-Guerrero

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Linolenic Acid ◽

Caspase 3 ◽

Colorectal Cancer Cell Line ◽

Human Colorectal Cancer ◽

Antitumor Effects ◽

Colorectal Cancer Cells ◽

Microscopy Images ◽

Ht 29

Abstract α-Linolenic acid (ALA, 18:3n-3) and γ-gamma linolenic acid (GLA, 18:3n-6) are polyunsaturated fatty acids (PUFA) that improve the human health. The present study focused on testing the in vitro antitumor actions of pure ALA and GLA on the HT-29 human colorectal cancer cell line. Cell viability was checked by MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test, cell membrane damage by the lactate dehydrogenase assay, apoptosis was tested by both caspase-3 activity trial and transmission electron microscopy images, and protein composition was analyzed by quantitative proteomics analysis. MTT test revealed IC50 values of 230 and 255 μM for ALA and GLA, respectively, at 72 h. After 24 h of incubation, both ALA and GLA induced apoptosis on HT-29 colorectal cancer cells according to the caspase-3 assay and microscopy images. SWATH/MS analysis evidenced that ALA significantly affected the mitochondrial protein import pathway and the citric acid cycle pathway, while GLA did not significantly affect any particular pathway. In summary, both ALA and GLA showed concentration-dependent inhibitory effects on HT-29 cells viability and induced cell death by apoptosis. ALA significantly affected cellular pathways, while GLA does not have specific actions on either pathway. Both n-3 and n-6 C18 PUFA are bioactive food components useful in the colorectal cancer prevention.

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Production of nanoliposomes with piperine from black pepper (Piper nigrum) and its improved growth inhibitory activity on colorectal cancer cells

Vietnam Journal of Biotechnology ◽

10.15625/1811-4989/18/4/16086 ◽

2021 ◽

Vol 18 (4) ◽

pp. 671-678

Author(s):

Le Nhat Minh ◽

Tran Thi Minh Anh ◽

Tran Van Loc ◽

Phung Thi Kim Hue ◽

Do Thi Thao

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Biological Activities ◽

Black Pepper ◽

Piper Nigrum ◽

Cytotoxic Activities ◽

Growth Inhibitory ◽

Colorectal Cancer Cells ◽

Ht 29

Black pepper (Piper nigrum) is an autoicous and decorous vine cultivated in many local regions of Gia Lai. Black pepper is one of the most commonly consumed spices, and its pungency is due to the presence of alkaloids, such as piperine. This compound represents diverse biological activities, including anti-inflammatory, anticancer, antiviral, anti-larvicidal, pesticide, anti-alzheimer’s activities, etc. However, due to its poor solubility as well as its toxic effects at high use concentration, piperine is still in limit of pharmaceutical applications. In this study, we have used black pepper seed collected at Chu Se - Gia Lai to extract piperine. The compound extracted efficiency was approximately 18% with 96.7% of purity. Based on the obtained pure piperine, the hybrid nanopiperine-CD133 monoclonal antibody (mAb^CD133) complexes were fabricated with the nanoparticle size of about 170 nm, the polydispersity index (PDI) of 0.23 and the zeta potential of -9.4 mV. The nanocomplex was subjected for growth inhibitory activities against cancer colorectal cells (HT-29 cell line). The results showed that the nanopiperine-mAb^CD133 complex exhibited significant in vitro growth inhibition HT-29 colorectal cancer cells (46.56 ± 2.78%), while the viability of healthy cells remained unaffected (17.77 ± 0.82 %). The nanocomplex could also label 12.17% of HT-29 cells, which was rather higher than 3.83% from mAb^CD133 conjugated phycoerythrin (PE) as positive control. The fabricated nanopiperine-mAb^CD133 complex has proved the enhanced cytotoxic activities against colorectal cancerous cells as well as promising biopharmaceutical potency.

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