scholarly journals Chitosan-Based Microparticles Enhance Ellagic Acid’s Colon Targeting and Proapoptotic Activity

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 652 ◽  
Author(s):  
Nabil A. Alhakamy ◽  
Osama A. A. Ahmed ◽  
Mallesh Kurakula ◽  
Giuseppe Caruso ◽  
Filippo Caraci ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Annexin V ◽  
High Elevation ◽  
Colon Cancer Cells ◽  
Colon Targeting ◽  
M Phase ◽  
Hct 116 ◽  
Cell Fractions

This study aimed at improving the targeting and cytotoxic effect of ellagic acid (EA) on colon cancer cells. EA was encapsulated in chitosan (CHIT) polymers then coated by eudragit S100 (ES100) microparticles. The release of EA double-coated microparticles (MPs) was tested at simulative pH values. Maximum release was observed at 24 h and pH 7.4. The cytotoxicity of EA MPs on HCT 116 colon cancer cells was synergistically improved as compared with raw EA. Cell-cycle analysis by flow cytometry suggested enhanced G2-M phase colon cancer cell accumulation. In addition, a significantly higher cell fraction was observed in the pre-G phase, which highlighted the enhancement of the proapoptotic activity of EA formulated in the double-coat mixture. Annexin-V staining was used for substantiation of the observed cell-death-inducing activity. Cell fractions were significantly increased in early, late, and total cell death. This was backed by high elevation in cellular content of caspase 3. Effectiveness of the double-coated EA to target colonic tissues was confirmed using real-time iohexol dye X-ray radiography. In conclusion, CHIT loaded with EA and coated with ES100 formula exhibits improved colon targeting as well as enhanced cytotoxic and proapoptotic activity against HCT 116 colon cancer when compared with the administration of raw EA.

scholarly journals Chitosan Coated Microparticles Enhance Simvastatin Colon Targeting and Pro-Apoptotic Activity

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 226 ◽  
Author(s):  
Nabil A. Alhakamy ◽  
Usama A. Fahmy ◽  
Osama A. A. Ahmed ◽  
Giuseppe Caruso ◽  
Filippo Caraci ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Annexin V ◽  
Entrapment Efficiency ◽  
Cell Fraction ◽  
Colon Cancer Cells ◽  
Colon Targeting ◽  
Eudragit S100 ◽  
Hct 116 ◽  
Apoptotic Activity

This work aimed at improving the targeting and cytotoxicity of simvastatin (SMV) against colon cancer cells. SMV was encapsulated in chitosan polymers, followed by eudragit S100 microparticles. The release of SMV double coated microparticles was dependent on time and pH. At pH 7.4 maximum release was observed for 6 h. The efficiency of the double coat to target colonic tissues was confirmed using real-time X-ray radiography of iohexol dye. Entrapment efficiency and particle size were used in the characterization of the formula. Cytotoxicity of SMV microparticles against HCT-116 colon cancer cells was significantly improved as compared to raw SMV. Cell cycle analysis by flow cytomeric technique indicated enhanced accumulation of colon cancer cells in the G2/M phase. Additionally, a significantly higher cell fraction was observed in the pre-G phase, which highlighted enhancement of the proapoptotic activity of SMV prepared in the double coat formula. Assessment of annexin V staining was used for confirmation. Cell fraction in early, late and total cell death were significantly elevated. This was accompanied by a significant elevation of cellular caspase 3 activity. In conclusion, SMV-loaded chitosan coated with eudragit S100 formula exhibited improved colon targeting and enhanced cytotoxicity and proapoptotic activity against HCT-116 colon cancer cells.

Abstract 3957: Cell death and growth arrest pathways mediating the actions of stilbene 5C in HCT-116 colon cancer cells

2012 ◽  
Author(s):  
Moureq R. Alotaibi ◽  
Matthew J. Beckman ◽  
Xu Di ◽  
Ray Lee ◽  
David A. Gewirtz
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Growth Arrest ◽  
Colon Cancer Cells ◽  
Hct 116

Effect of inhibition of nuclear protein export using a novel CRM1 inhibitor on the apoptotic response to SN38 in preclinical colon cancer models.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 609-609 ◽  
Author(s):  
Hye Won Chung ◽  
Roberto A. Salas Fragomeni ◽  
Sharon Shacham ◽  
Michael Kauffman ◽  
James C. Cusack
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Synergistic Effect ◽  
Cancer Cells ◽  
Topoisomerase I ◽  
Annexin V ◽  
Elisa Assay ◽  
Colon Cancer Cells ◽  
Cell Death Detection Elisa ◽  
Ht29 Cells

609 Background: Resistance to conventional chemotherapy remains a major challenge in Stage IV colon cancer. CRM1 inhibition leads to nuclear sequestration of proteins such as tumor suppressor p53, growth regulatory proteins, and chemotherapy targets such as topoisomerase I/II. We examined the effects of combination use of KPT185 (a novel CRM1 inhibitor) with SN38 (active metabolite of irinotecan) and the effect of drug administration sequence in human colon cancer cell lines to determine if CRM1 inhibition enhances the cytotoxic effect of chemotherapy. Methods: We evaluated the combination effect of KPT185 with SN-38 on both Lovo (KPT-sensitive, IC50 = ∼ 500nM) and HT29 cells (KPT-resistant, IC50 = 1000 ∼ 3000nM) by the Chou-Talalay method, an MTT-based assay that interrogates response across a spectrum of drug dosages: KPT185 (0, 1, 10, 100, 1000, 10000 nM) and SN38 (0, 100, 500, 1000 nM). Cell cycle analysis by FACS with propidium iodide (PI) staining was performed. Effects on apoptosis were determined by FACS (Annexin V/PI staining) and Cell Death Detection ELISA assay. Results: The Chou-Talalay method determined that there is a synergistic effect when KPT185 is combined with SN38 in both Lovo and HT29 cells (combination index > 1). FACS analysis demonstrated combination use of KPT185 and SN38 induced an increase in the apoptotic sub-G1 fraction and a shift toward G2/M arrest. Combination treatment also significantly increased the Annexin V/PI-positive fraction compared with SN38 alone case (P < 0.05). Treatment sequence studies demonstrated that pretreatment of SN38 followed by KPT185 (KPT-post) produced the maximum synergistic effect compared with pretreatment of KPT185 followed by SN38 (KPT-pre) or concurrent use (KPT-con); Cell Death Detection ELISA assay showed KPT-post increased apoptosis most (4.3-fold) compared with KPT-pre (4.2-fold), KPT-con (3.8-fold) and SN38 alone (1-fold). Conclusions: Our results show KPT185, a novel CRM1 inhibitor, sensitizes the response to SN38 in KPT-sensitive as well as KPT-resistant colon cancer cells. This method of sensitizing colon cancer cells warrants further evaluation in preclinical models of colon cancer.

Translation inhibition during cell cycle arrest and apoptosis: Mcl-1 is a novel target for RNA binding protein CUGBP2

2008 ◽  
Vol 294 (4) ◽  
pp. G1025-G1032 ◽  
Author(s):  
Dharmalingam Subramaniam ◽  
Gopalan Natarajan ◽  
Satish Ramalingam ◽  
Ilangovan Ramachandran ◽  
Randal May ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Rna Binding ◽  
Mrna Translation ◽  
Cyclin B1 ◽  
Colon Cancer Cells ◽  
Translation Inhibition ◽  
M Phase ◽  
Hct 116

CUGBP2, a translation inhibitor, induces colon cancer cells to undergo apoptosis. Mcl-1, an antiapoptotic Bcl-2 family protein, interferes with mitochondrial activation to inhibit apoptosis. Here, we have determined the effect of CUGBP2 on Mcl-1 expression. We developed a HCUG2 cell line by stably expressing CUGBP2 in the HCT-116 colon cancer cells. HCUG2 cells demonstrate decreased levels of proliferation and increased apoptosis, compared with HCT-116 cells. Flow cytometry analysis demonstrated higher levels of cells in the G2-M phase. Western blot analyses demonstrated that there was decreased Bcl-2 and Mcl-1 protein but increased expression of Bax, cyclin B1, and Cdc2. Immunocytochemistry also demonstrated increased levels of cyclin B1 and Cdc2 in the nucleus of HCUG2 cells. However, there was colocalization of phosphorylated histone H3 with transferase-mediated dUTP nick-end labeling (TUNEL). Furthermore, immunostaining for α-tubulin demonstrated that there was disorganization of microtubules. These data suggest that CUGBP2 expression in HCUG2 cells induces the cells to undergo apoptosis during the G2-M phase of the cell cycle. We next determined the mechanism of CUGBP2-mediated reduction in Mcl-1 expression. Mcl-1 protein, but not Mcl-1 mRNA, was lower in HCUG2 cells, suggesting translation inhibition. CUGBP2 binds to Mcl-1 3′-untranslated region (3′-UTR) both in vitro and in HCUG2 cells. Furthermore, CUGBP2 increased the stability of both endogenous Mcl-1 and luciferase mRNA containing the Mcl-1 3′-UTR. However, luciferase protein expression from the luciferase-Mcl-1 3′-UTR mRNA was suppressed. Taken together, these data demonstrate that CUGBP2 inhibits Mcl-1 expression by inhibiting Mcl-1 mRNA translation, resulting in driving the cells to apoptosis during the G2 phase of the cell cycle.

scholarly journals Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1261
Author(s):  
Nurul Fattin Che Rahim ◽  
Yazmin Hussin ◽  
Muhammad Nazirul Mubin Aziz ◽  
Nurul Elyani Mohamad ◽  
Swee Keong Yeap ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Lines ◽  
Curcuma Longa ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Sw620 Cell

Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012–2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.

scholarly journals Ultrasound-enhanced biosynthesis of uniform ZnO nanorice using Swietenia macrophylla seed extract and its in vitro anticancer activity

2021 ◽  
Vol 10 (1) ◽  
pp. 572-585
Author(s):  
Darren Yi Sern Low ◽  
Camille Keisha Mahendra ◽  
Janarthanan Supramaniam ◽  
Loh Teng Hern Tan ◽  
Learn Han Lee ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Hexagonal Wurtzite Structure ◽  
Colon Cancer Cells ◽  
Swietenia Macrophylla ◽  
Zno Nps ◽  
Human Colon Cancer ◽  
Hct 116

Abstract In this study, ultrasonically driven biosynthesis of zinc oxide nanoparticles (ZnO NPs) using Swietenia macrophylla seed ethyl acetate fraction (SMEAF) has been reported. X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) analyses confirmed the presence of a pure hexagonal wurtzite structure of ZnO. Field emission scanning electron microscope images revealed the formation of uniquely identifiable uniform rice-shaped biologically synthesized ZnOSMEAF particles. The particle sizes of the biosynthesized NPs ranged from 262 to 311 nm. The underlying mechanisms for the biosynthesis of ZnOSMEAF under ultrasound have been proposed based on FTIR and XRD results. The anticancer activity of the as-prepared ZnOSMEAF was investigated against HCT-116 human colon cancer cell lines via methyl thiazolyl tetrazolium assay. ZnOSMEAF exhibited significant anticancer activity against colon cancer cells with higher potency than ZnO particles prepared using the chemical method and SMEAF alone. Exposure of HCT-116 colon cancer cells to ZnOSMEAF promoted a remarkable reduction in cell viability in all the tested concentrations. This study suggests that green sonochemically induced ZnO NPs using medicinal plant extract could be a potential anticancer agent for biomedical applications.

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