Folate-Functionalized Amphiphilic Chitosan Polymeric Micelles Containing Andrographolide Analogue (3A.1) for Colorectal Cancer

2019 ◽  
Vol 819 ◽  
pp. 15-20
Author(s):  
Teeratas Kansom ◽  
Ekachai Dumkliang ◽  
Prasopchai Patrojanasophon ◽  
Warayuth Sajomsang ◽  
Rungnapha Saeeng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Physicochemical Properties ◽  
Cancer Cells ◽  
Delivery System ◽  
Polymeric Micelles ◽  
Loading Capacity ◽  
Site Specific ◽  
Anticancer Efficacy ◽  
Colorectal Cancer Cells

A site-specific drug delivery system of anticancer agents has been delveloped to enhance the therapeutic efficacy and reduce toxicity to the normal tissue. Semi-synthetic andrographolide analogue 3A.1 (19-tert-butyldiphenylsilyl-8,17-epoxy andrographolide) is one of the potential natural anticancer compounds against many types of cancer including colorectal cancer cells. However, the clinical applications of this compound are limited because of low water solubility and lack of suitable delivery carriers. This study aimed to increase the aqueous solubility and improve the anticancer efficacy of 3A.1 via active targeting approaches. In this study, 3A.1 was loaded into the polymeric micelles self-assembled from N-naphthyl-N,O-succinyl chitosan (NSC). The micelles were conjugated with folate moiety (Fol-NSC) for targeting to the cancer cells. All of the 3A.1-loaded micelles were prepared by dropping method, and the physicochemical properties (size, charge, morphology, encapsulating efficiency, loading capacity), in vitro release behavior and in vitro anticancer activities against HT29 colorectal cancer cells were investigated. The 3A.1-loaded micelles were successfully formulated by dropping method using NSC or Fol-NSC. The micelles loaded with 40% initial 3A.1 showed the maximum encapsulating efficiency and loading capacity. The micelles were in the nanometer range, having a negative surface charge and a spherical structure. The colon site-specific release of the 3A.1 from the 3A.1-loaded micelles was obtained. The release of 3A.1 from the Fol-NSC micelles was slower than that from the NSC micelles. Moreover, the Fol-NSC micelles exhibited superior anticancer efficacy than that of the NSC micelles and free 3A.1. In conclusions, the 3A.1-loaded Fol-NSC micelles developed in the present study had suitable physicochemical properties. These nanocarriers may be a potential delivery system for targeted delivery of the 3A.1 to colorectal cancer cells.

scholarly journals Preparation and Characterization of Self Nano-Emulsifying Drug Delivery System Loaded with Citraland Its Antiproliferative Effect on Colorectal Cells In Vitro

Nanomaterials ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 1028 ◽  
Author(s):  
Mira Nadiah Mohd Izham ◽  
Yazmin Hussin ◽  
Muhammad Nazirul Mubin Aziz ◽  
Swee Keong Yeap ◽  
Heshu Sulaiman Rahman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Drug Delivery System ◽  
Delivery System ◽  
Average Particle Size ◽  
Physicochemical Characterization ◽  
Average Particle ◽  
Colorectal Cancer Cells

Citral is an active compound naturally found in lemongrass, lemon, and lime. Although this pale-yellow liquid confers low water solubility, the compound has been reported to possess good therapeutic features including antiproliferative and anticancer modalities. The self nano-emulsifying drug delivery system (SNEDDS) is a type of liquid-lipid nanocarrier that is suitable for the loading of insolubilized oil-based compound such as Citral. This study reports the design and optimization of a SNEDDS formulation, synthesis and characterization as well as loading with Citral (CIT-SNEDDS). Further assessment of theantiproliferative effects of CIT-SNEDDS towards colorectal cancer cells was also conducted. SNEDDS composed of coconut oil, dimethyl sulfoxide (DMSO) and Tween 80. CIT-SNEDDS was prepared via gentle agitation of SNEDDS with 0.5% Citral for 72 h at room temperature. Physicochemical characterization was performed using several physicochemical analyses. The average particle size of CIT-SNEDDS was16.86 ± 0.15 nm, zeta potential of 0.58 ± 0.19 mV, and polydispersity index (PDI) of 0.23 ± 0.01. In vitro drug release of Citral from CIT-SNEDDS was 79.25% of release, and for Citral the release percentage was 93.56% over 72 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was done to determine the cytotoxicity effect of CIT-SNEDDS in human colorectal cancer cell lines HT29 and SW620. The half maximal inhibitory concentrations (IC50) for 72 hof CIT-SNEDDS and Citral on SW620 were 16.50 ± 0.87 µg/mL and 22.50 ± 2.50 µg/mL, respectively. The IC50 values of CIT-SNEDDS and Citral after 72 h of treatment on HT29 were 34.10 ± 0.30 µg/mL and 21.77 ± 0.23 µg/mL, respectively. This study strongly suggests that CIT-SNEDDS has permitted the sustained release of Citral and that CIT-SNEDDS constitutes a potential soluble drug nanocarrier that is effective against colorectal cancer cells.

The Antitumor Activity of Betulinic Acid-Loaded Nanoliposomes Against Colorectal Cancer In Vitro and In Vivo via Glycolytic and Glutaminolytic Pathways

2020 ◽  
Vol 16 (2) ◽  
pp. 235-251
Author(s):  
Gang Wang ◽  
Yu-Zhu Wang ◽  
Yang Yu ◽  
Pei-Hao Yin ◽  
Ke Xu
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Betulinic Acid ◽  
Anticancer Efficacy ◽  
Anti Cancer ◽  
Colorectal Cancer Cells ◽  
Cellular Apoptosis

The purpose of this study is to develop betulinic acid loaded nanoliposomes to improve the chemotherapy effect of colorectal cancer. The cellular uptake and anti-tumor effects of betulinic acid loaded nanoliposomes in vitro were characterized and evaluated, and their effects on glycolysis, glutamine decomposition and key anti-cancer targets were analyzed. Moreover, their anticancer efficacy was assessed in vivo. Compared with free betulinic acid in vitro, the cellular uptake and anti-tumor activity of betulinic acid-loaded nanoliposomes were significantly enhanced; these nanoliposomes significantly suppressed the proliferation and glucose uptake of colorectal cancer cells. Mechanistically, the anti-colorectal cancer effect of betulinic acid-loaded nanoliposomes was confirmed by their triggering of cellular apoptosis and regulating the potential glycolytic and glutaminolytic targets and pathways. After tumor proliferation was inhibited and colorectal cancer cells apoptosis, the anticancer effect of betulinic acid loaded nanoliposomes in vivo was significantly enhanced. All in all, betulinic acid loaded nanoliposomes are expected to be an effective drug delivery system for colorectal cancer treatment.

scholarly journals Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Simona Mareike Lüttgenau ◽  
Christin Emming ◽  
Thomas Wagner ◽  
Julia Harms ◽  
Justine Guske ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Scaffolding Protein ◽  
Migration And Invasion ◽  
Tight Junction Formation ◽  
Cell Metastasis ◽  
Colorectal Cancer Cells

AbstractLoss of apical-basal polarity and downregulation of cell-cell contacts is a critical step during the pathogenesis of cancer. Both processes are regulated by the scaffolding protein Pals1, however, it is unclear whether the expression of Pals1 is affected in cancer cells and whether Pals1 is implicated in the pathogenesis of the disease.Using mRNA expression data and immunostainings of cancer specimen, we show that Pals1 is frequently downregulated in colorectal cancer, correlating with poorer survival of patients. We further found that Pals1 prevents cancer cell metastasis by controlling Rac1-dependent cell migration through inhibition of Arf6, which is independent of the canonical binding partners of Pals1. Loss of Pals1 in colorectal cancer cells results in increased Arf6 and Rac1 activity, enhanced cell migration and invasion in vitro and increased metastasis of transplanted tumor cells in mice. Thus, our data reveal a new function of Pals1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells. Notably, this new function is independent of the known role of Pals1 in tight junction formation and apical-basal polarity.

scholarly journals Dehydrodiisoeugenol inhibits colorectal cancer growth by endoplasmic reticulum stress-induced autophagic pathways

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Changhong Li ◽  
Kui Zhang ◽  
Guangzhao Pan ◽  
Haoyan Ji ◽  
Chongyang Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endoplasmic Reticulum ◽  
Cell Growth ◽  
Er Stress ◽  
Cancer Cells ◽  
Tumor Xenograft ◽  
Anticancer Activities ◽  
Colorectal Cancer Cells

Abstract Background Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated. Methods In this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo. Results Our findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models. Conclusions Collectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.

scholarly journals MicroRNA-124 Regulates the Proliferation of Colorectal Cancer Cells by TargetingiASPP

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Kuijie Liu ◽  
Hua Zhao ◽  
Hongliang Yao ◽  
Sanlin Lei ◽  
Zhendong Lei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Target Prediction ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Small Noncoding Rnas ◽  
Colorectal Cancer Cells ◽  
Microrna 124

MicroRNAs are a class of small, noncoding RNAs that function as critical regulators of gene expression by targeting mRNAs for translational repression or degradation. In this study, we demonstrate that expression of microRNA-124 (miR-124) is significantly downregulated in colorectal cancer tissues and cell lines, compared to the matched adjacent tissues. We identified and confirmed inhibitor of apoptosis-stimulating protein of p53 (iASPP) as a novel, direct target of miR-124 using target prediction algorithms and luciferase reporter gene assays. Overexpression of miR-124 suppressed iASPP protein expression, upregulated expression of the downstream signaling molecule nuclear factor-kappa B (NF-κB), and attenuated cell viability, proliferation, and colony formation in SW480 and HT-29 colorectal cancer cells in vitro. Forced overexpression ofiASPPpartly rescued the inhibitory effect of miR-124 on SW480 and HT29 cell proliferation. Taken together, these findings shed light on the role and mechanism of action of miR-124, indicate that the miR-124/iASPP axis can regulate the proliferation of colorectal cancer cells, and suggest that miR-124 may serve as a potential therapeutic target for colorectal cancer.

scholarly journals Current Status, Distribution, and Future Directions of Natural Products against Colorectal Cancer in Indonesia: A Systematic Review

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4984
Author(s):  
Didi Nurhadi Illian ◽  
Ihsanul Hafiz ◽  
Okpri Meila ◽  
Ahmad Rusdan Handoyo Utomo ◽  
Arif Nuryawan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Natural Products ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Cell Line ◽  
Current Status ◽  
Vitro Assay ◽  
Colorectal Cancer Cells

In 2020, an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths have occurred worldwide, with colorectal cancer ranking as the third most frequently diagnosed (10.0%). Several attempts have been conducted against cancer, including surgery, radiation, monoclonal antibodies, and chemotherapy. Many people choose natural products as alternatives against cancer. These products will not only help in human life preservation but also work as a source of up-to-date information, leading people away from incorrect information. We discuss the current status, distribution, and future implications of protecting populations with natural products as an alternative against colorectal cancer in Indonesia. Thirty-eight studies were included in this review for data extraction. The distribution of natural products in Indonesia that have potential activity against colorectal cancer cells was predominated by terpenoids, followed by phytosterols, phenolics, alkaloids, and polyisoprenoids. The type of cell line utilized in the cytotoxic activity analysis of natural products was the WiDr cell line, followed by HT-29 cells and HCT-116 cells. This review showed that MTT in vitro assay is a general method used to analyze the cytotoxic activity of a natural product against colorectal cancer cells, followed by other in vitro and in vivo methods. The systematic review provided predictions for several secondary metabolites to be utilized as an alternative treatment against colorectal cancer in Indonesia. It also might be a candidate for a future co-chemotherapy agent in safety, quality, and standardization. In addition, computational methods are being developed to predict the drug-likeness of compounds, thus, drug discovery is already on the road towards electronic research and development.

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