Ideal 1:1 stoichiometry curcumin inclusion complex induced potential apoptosisin colorectal adenocarcinoma cells: The clear image of necrosis and functionalized dying effect

2019 ◽  
Vol 14 ◽  
Author(s):  
Kavitha K ◽  
Muthu Mohamed J ◽  
Chitra Karthikeyini S
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cell Growth ◽  
Inclusion Complex ◽  
Colorectal Adenocarcinoma ◽  
Phase Solubility ◽  
Adenocarcinoma Cell ◽  
Adenocarcinoma Cells ◽  
Ic50 Value ◽  
Hot Melt

Background: This study investigates the inclusion complex of curcumin (CMN) enhance the solubility, which can be utilized for the treatment of colorectal cancer (CRC) greater to free CMN. Methods: CMN solid dispersion (SD) prepared by a hot melt method using CMN with several carriers of poloxamers (P-407 and P-188), gelucire 50/13 (GLR) and mannitol (MNT). Prior, molecular modelling and phase solubility studieswere performed with drug and carriers. The SD characterized by in vitrodrug release, SEM and functionalize dyeing test. Additionally, the cytotoxicity and image of apoptosisresolved to utilize the colorectal adenocarcinoma cell lines. Results: The result showed that CMN-P-407 inclusion complex produced significant properties towards solubility (318 ± 14.46 fold) and dissolution (91 ± 0.431% at 30 min). Similarly, these data fit with insilico model. The IC50 value for inclusion complex found to be 74 and 52 µM/mL, while that for free CMN ranged from 146 and 116 µM/mL on the SW480 and Caco-2 cells respectively. Apoptosis study described that the cells are undergoing cell death by apoptosis and the small number of necrosis. Conclusion: The profound efficiency of CMN-P-407 SD indicated its potential application for CRC treatment by showing a higher capability of inhibiting cell growth compared to that of free CMN.

Lysine-specific demethylase 2A expression is associated with cell growth and cyclin D1 expression in colorectal adenocarcinoma

2018 ◽  
Vol 33 (4) ◽  
pp. 407-414 ◽  
Author(s):  
Lin-Lin Cao ◽  
Changzheng Du ◽  
Hangqi Liu ◽  
Lin Pei ◽  
Li Qin ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cyclin D1 ◽  
Colorectal Adenocarcinoma ◽  
Chain Reaction ◽  
Adenocarcinoma Cell ◽  
Lysine Specific Demethylase ◽  
Adenocarcinoma Cells ◽  
Polymerase Chain ◽  
And Function

Objective: Lysine-specific demethylase 2A (KDM2A), a specific H3K36me1/2 demethylase, has been reported to be closely associated with several types of cancer. In this study, we aimed to investigate the expression and function of KDM2A in colorectal adenocarcinoma. Methods: A total of 215 colorectal adenocarcinoma specimens were collected, and then subjected to immunohistochemistry assay to evaluate the expression levels of KDM2A, cyclin D1 and other proteins in colorectal adenocarcinoma tissues. Real-time polymerase chain reaction, Western blot, and other molecular biology methods were used to explore the role of KDM2A in colorectal adenocarcinoma cells. Results: In this study, we report that the expression level of KDM2A is high in colorectal adenocarcinoma tissues, and this high expression promotes the proliferation and colony formation of colorectal adenocarcinoma cells, as demonstrated by KDM2A knockdown experiments. In addition, the expression of KDM2A is closely associated with cyclin D1 expression in colorectal adenocarcinoma tissues and cell lines. Conclusions: Our study reveals a novel role for high-expressed KDM2A in colorectal adenocarcinoma cell growth, and that the expression of KDM2A is associated with that of cyclin D1 in colorectal adenocarcinoma.

scholarly journals Modulating Properties of Piroxicam, Meloxicam and Oxicam Analogues against Macrophage-Associated Chemokines in Colorectal Cancer

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7375
Author(s):  
Paulina Lewandowska ◽  
Izabela Szczuka ◽  
Iwona Bednarz-Misa ◽  
Berenika M. Szczęśniak-Sięga ◽  
Katarzyna Neubauer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Adenocarcinoma ◽  
Normal Mucosa ◽  
Colorectal Tumors ◽  
Adjacent Tissue ◽  
Inflammatory Drug ◽  
Chemokine Expression ◽  
Adenocarcinoma Cells ◽  
Thiazine Ring ◽  
N Stage

The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the expression/secretion of macrophage-associated chemokines (RTqPCR/Luminex xMAP) in colorectal adenocarcinoma cells, and on the expression of upstream the non-steroidal anti-inflammatory drug (NSAID)-activated genes NAG1, NFKBIA, MYD88, and RELA, as well as at the chemokine profiling in colorectal tumors. Meloxicam downregulated CCL4 9.9-fold, but otherwise the classic oxicams had a negligible/non-significant effect. Novel analogues with a thiazine ring substituted with arylpiperazine and benzoyl moieties significantly modulated chemokine expression to varying degree, upregulated NAG1 and NFKBIA, and downregulated MYD88. They inhibited CCL3 and CCL4, and their effect on CCL2 and CXCL2 depended on the dose and exposure. The propylene linker between thiazine and piperazine nitrogens and one arylpiperazine fluorine substituent characterized the most effective analogue. Only CCL19 and CXCL2 were not upregulated in tumors, nor was CXCL2 in tumor-adjacent tissue compared to normal mucosa. Compared to adjacent tissue, CCL4 and CXCL2 were upregulated, while CCL2, CCL8, and CCL19 were downregulated in tumors. Tumor CCL2 and CCL7 increased along with advancing T and CCL3, and CCL4 along with the N stage. The introduction of arylpiperazine and benzoyl moieties into the oxicam scaffold yields effective modulators of chemokine expression, which act by upregulating NAG1 and interfering with NF-κB signaling.

A serine protease extracted from Trichosanthes kirilowii induces apoptosis via the PI3K/AKT-mediated mitochondrial pathway in human colorectal adenocarcinoma cells

2016 ◽  
Vol 7 (2) ◽  
pp. 843-854 ◽  
Author(s):  
Li Song ◽  
Jiao Chang ◽  
Zhuoyu Li
Keyword(s):  
Colorectal Cancer ◽  
Serine Protease ◽  
Colorectal Adenocarcinoma ◽  
Mitochondrial Pathway ◽  
Adenocarcinoma Cells ◽  
Trichosanthes Kirilowii ◽  
Dependent Pathway ◽  
Cancer Activity ◽  
Novel Protein

A novel protein TKP extracted from T. kirilowii fruit exerted potential anti-colorectal cancer activity by inducing apoptosis, which was regulated by the PI3K/AKT-mediated mitochondria-dependent pathway.

scholarly journals Preparation of Soluble Complex of Curcumin for the Potential Antagonistic Effects on Human Colorectal Adenocarcinoma Cells

2021 ◽  
Vol 14 (9) ◽  
pp. 939
Author(s):  
Jamal Moideen Muthu Mohamed ◽  
Ali Alqahtani ◽  
Barkat A. Khan ◽  
Adel Al Fatease ◽  
Taha Alqahtani ◽  
...  
Keyword(s):  
Aqueous Solubility ◽  
In Vitro Cytotoxicity ◽  
Phase Solubility ◽  
Soluble Complex ◽  
Zebrafish Model ◽  
Adenocarcinoma Cells ◽  
Hot Melt ◽  
Central Composite

This study was designed to investigate the effects of curcumin (CMN) soluble complex (SC) prepared by melt casting (HM) and hot-melt extrusion (HME) technology. Phase solubility (PS) study, in silico molecular modeling, aqueous solubility, drug release, and physicochemical investigation including a novel dyeing test was performed to obtain an optimized complex by a central composite design (CCD). The results show that the HME-SC produces better improvements towards solubility (0.852 ± 0.02), dissolution (91.87 ± 0.21 % at 30 min), with an ideal stability constant (309 and 377 M−1 at 25 and 37 °C, respectively) and exhibits AL type of isotherm indicating 1:1 stoichiometry. Intermolecular hydrogen bonding involves the formation of SC, which does not undergo any chemical modification, followed by the complete conversion of the amorphous form which was identified by XRD. The in vitro cytotoxicity showed that IC50 was achieved in the SW480 (72 µM.mL−1) and Caco-2 (40 µM.mL−1) cells while that of pure CMN ranged from 146 to 116 µM/mL−1. Apoptosis studies showed that cell death is primarily due to apoptosis, with a low rate of necrosis. In vivo toxicity, confirmed by the zebrafish model, exhibited the safety of the HME-SC. In conclusion, the HME-SC potentially enhances the solubility and cytotoxicity to the treatment of colorectal cancer (CRC).

scholarly journals Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death

2010 ◽  
Vol 67 (5) ◽  
pp. 1167-1178 ◽  
Author(s):  
Bettina M. Kaminski ◽  
Andreas Weigert ◽  
Bernhard Brüne ◽  
Marco Schumacher ◽  
Uwe Wenzel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Growth Inhibition ◽  
Colorectal Cancer Cells

scholarly journals Expression of HER2 in Colorectal Cancer Does Not Correlate with Prognosis

2010 ◽  
Vol 29 (5) ◽  
pp. 207-212 ◽  
Author(s):  
Wiesław Janusz Kruszewski ◽  
Robert Rzepko ◽  
Maciej Ciesielski ◽  
Jarosław Szefel ◽  
Jacek Zieliński ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Membrane ◽  
Predictive Factor ◽  
Colorectal Adenocarcinoma ◽  
Prognostic Significance ◽  
Staining Intensity ◽  
Her2 Expression ◽  
Prognostic Information ◽  
Adenocarcinoma Cells ◽  
Entire Cell

Estimation of HER2 membranous expression is routinely used in breast and gastric cancers, as both a prognostic and a predictive factor. To date there is no evidence for similar application of HER2 expression in colorectal cancer (CRC) cells. In CRC, HER2 is sometimes overexpressed in the cell membrane and very often in the cytoplasm. This study was conducted to determine possible correlations between both membranous and cytoplasmatic expression of HER2 in CRC cells and the outcome of the disease. The prognostic significance of combined staining intensity in the cell membrane and cytoplasm in the entire CRC cell was also investigated. HER2 expression in resectable colorectal adenocarcinoma cells was evaluated by immunohistochemistry in specimens taken from 202 patients. The percentage of cancer cells with membranous or cytoplasmatic reactions and the staining intensity of the reaction in the whole cell were recorded. A membranous reaction was present in 27% of cases, and cytoplasmatic reaction in 66% of cases. The total staining intensity in the entire cell was evaluated as moderate (2+) in 32% of cases and strong (3+) staining in 15%. There was no correlation found between either membranous or cytoplasmatic HER2 expression and survival. Furthermore combined staining intensity did not provide any prognostic information. We conclude that HER2 expression in CRC does not correlate with prognosis.

scholarly journals Serum DJ-1 Is a Biomarker of Colorectal Cancer and DJ-1 Activates Mitophagy to Promote Colorectal Cancer Progression

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4151
Author(s):  
William Tzu-Liang Chen ◽  
Han-Bin Yang ◽  
Tao-Wei Ke ◽  
Wen-Ling Liao ◽  
Shih-Ya Hung
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Colorectal Adenocarcinoma ◽  
Reactive Oxygen Species Generation ◽  
Cancer Drug ◽  
Adenocarcinoma Cells ◽  
Colorectal Cancer Progression ◽  
Colorectal Cancer Patients

Colorectal cancer is the second most common cancer and the third cancer-associated death in Taiwan. Currently used serum markers for detecting colorectal cancer lack excellent diagnostic accuracy, which results in colorectal cancer being often recognized too late for successful therapy. Mitophagy is the selective autophagic degradation of damaged or excessive mitochondria. DJ-1 is an antioxidant protein that attenuates oxidative stress and maintains mitochondrial quality through activating mitophagy. Mitophagy activation contributes to anti-cancer drug resistance. However, the role of DJ-1-induced mitophagy in colorectal cancer progression remains unclear. In the present study, we collected matched tumor and adjacent normal tissues and serum from patients and cancer cells to demonstrate the clinical value and physiological function of DJ-1 in colorectal cancer. We found that DJ-1 increased in tumor tissues and serum; it was positively correlated with TNM (tumor-node-metastasis) stages of colorectal cancer patients. Through stable knockdown DJ-1 expression in metastatic colorectal adenocarcinoma cells SW620, DJ-1 knockdown inhibited cancer cell survival, migration, and colony formation. In SW620 cells, DJ-1 knockdown induced an incomplete autophagic response that did not affect ATP production; DJ-1 knockdown enhanced intracellular reactive oxygen species generation and damaged mitochondrial accumulation and mitophagy inhibition. It suggests that DJ-1 knockdown inhibits mitophagy that causes metastatic colorectal adenocarcinoma cells to be unable to remove damaged mitochondria and further enhance cancer cell apoptosis. Our data indicate that DJ-1 might be clinically valuable as serum and tissue biomarkers for predicting the TNM stage in colorectal cancer patients. Since DJ-1-induced mitophagy promotes tumor progression, DJ-1 inhibition is a potential therapeutic strategy for colorectal cancer treatment.

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