Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 113 ◽  
Author(s):  
Alaa A. A. Aljabali ◽  
Hamid A. Bakshi ◽  
Faruck L. Hakkim ◽  
Yusuf A. Haggag ◽  
Khalid M. Al-Batanyeh ◽  
...  

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC–BSA nanoparticles (NPs). These PIC–BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC–BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC–BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC–BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC–BSA NPs, enhances its therapeutic potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possible human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.


2017 ◽  
Vol 12 (2) ◽  
pp. 196-200 ◽  
Author(s):  
Samira Rasouli Koohi ◽  
Mohammad Ali Derakhshan ◽  
Faramarz Faridani ◽  
Samad Muhammad Nejad ◽  
Saeid Amanpour ◽  
...  

Author(s):  
Mayson Alkhatib ◽  
Retnowati . ◽  
Amalia F.

Combining drugs with different mechanism of action in nanocarriers is becoming a promising strategy in cancer therapy. In the present study, the anticancer activity of the combination of doxorubicin (DOX) and pravastatin (PRV) loaded in nanoemulsions (NEs) was evaluated in HCT 116 colon cancer cells. The NE formulas (NEa and NEb) consisted of different weight fractions of the surfactant mixture of Eumulgin HRE 40/ Soya phosphatidylcholine/ sodium oleate at a fixed weight ratio of 3.5:3.0:3.5, cholesterol (CHO), Tris- HCl buffer (pH 7.22), and 1-octanol. The cytotoxicity of the drug formulas, loaded in either water or NEs, was assessed through 3-(4, 5 Dimethylthiazole- 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, while the mechanism of cell death was determined by observing the morphological changes of treated cells under light microscope and identifying apoptosis by using the ApopNexin FITC kit and DAPI nuclear staining. It has been found that reducing the concentration of DOX from 15 to 7.5µM by formulating it with 7.5µM of PRV in NEa (NEa (1 DOX:1 PRV)) has preserved its cytotoxicity against HCT-116 cancer cells. The present study proved that the combination of the PRV and DOX loaded in NEa formulations improved the therapeutic potential of both of PRV and DOX as anticancer drugs.


Author(s):  
Mohd Adzim Khalili Rohin ◽  
Norhayati Abd Hadi ◽  
Norhaslinda Ridzwan

Aims: To examine the anti-proliferative properties of different extracts of new variety an organic rice MRQ74 towards colon cancer cells: in-vitro study. Study Design: Experimental study. Place and Duration of Study: Central Laboratory, Tissue Culture Laboratory, University of Sultan Zainal Abidin, Terengganu from November 2019 until February 2020. Methodology: The organic rice MRQ74 extracts had been led to tetrazolium salt reduction (MTT) assay and an inhibition concentration of 50 (IC50) value for their cytotoxic potential against colon cancer cells. Meanwhile, cells morphology observation and fluorescence double staining of treatment cells were determined using a light inverted microscope and acridine orange/propidium iodide staining. Results: Results showed that 50% aqueous ethanol of rice grains gave the lowest IC50 values towards HCT-116 and CT-26 cell lines, while an aqueous solution of rice grains gave the lowest IC50 values towards HT-29 cells (p<0.05). Thoroughly, the treated colon cancer cells had shown morphological alterations after treated with different solvent extracts of an organic rice MRQ74. Conclusion: The outcomes had observed preliminary results on cancer study for better health by inspiring the consumption of an organic rice MRQ74 and future product developments.


2017 ◽  
Vol 18 (7) ◽  
pp. 1396 ◽  
Author(s):  
Magdalena Fic ◽  
Agnieszka Gomulkiewicz ◽  
Jedrzej Grzegrzolka ◽  
Marzenna Podhorska-Okolow ◽  
Maciej Zabel ◽  
...  

Author(s):  
Mattias Lepsenyi ◽  
Nader Algethami ◽  
Amr A. Al-Haidari ◽  
Anwar Algaber ◽  
Ingvar Syk ◽  
...  

AbstractPeritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.


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