scholarly journals Cytotoxicity and Cellular Uptake of 5-Fluorouracil Loaded Methylcellulose Nanohydrogel for Treatment of Oral Cancer

2020 ◽  
Vol 10 (1) ◽  
pp. 1904-1918

The objective of the study was to investigate the cytotoxicity and cellular uptake of prepared 5-Fluorouracil (5-FU) nano hydrogel formulation using KB oral cancer cell line and VERO fibroblast cell line. The biodegradable thermoresponsive modified methylcellulose (MMC) polymer was used for the preparation of nano hydrogel, whereas it shows a sol-gel phase transition at 36˚C to 40˚C. The physical crosslinking method was used, followed by probe sonication for the preparation of 5-FU loaded MMC nano hydrogel. The mechanism of crosslinking was studied by FT-IR and SEM. These experimental techniques explained physical crosslinking viz. H-bonding phenomenon with the interconnected porous structure of nanoscale pore size. Cytotoxicity assay in the concentration range from 1 µg/ml to 2000µg/ml shows an IC50 value at around 250µg/ml. This nano hydrogel shows concentration-dependent toxicity to the cancer cells while they were less toxic to normal fibroblast VERO cells. Cellular uptake was confirmed by the green fluorescence inside cells by Rhodamine-B conjugation using a fluorescent microscope. These results depict that 5-FU loaded thermosensitive nano hydrogel may be a promising candidate for intratumoral targeted drug delivery to cancer cells.

Author(s):  
Nenavath Vinay ◽  
Darling Chellathai David

Background: Cancer is rapidly evolving life-threatening ailment in the mankind due to changes in daily food intake and lifestyle changes. Oral carcinoma is 6th major cause of cancer death in the world and it is third major reason of cancer mortality in India. Every cell in the human body requires glucose for its metabolic energy. Besides normal cell, cancer cells also require the glucose for its endurance and multiplication. SGLT2 inhibitors which are aimed at diabetes therapy exhibited anticancer properties also in colon and pancreatic cancer lines. Present study aim is to evaluate the anticancer activity of SGLT2 inhibitors against oral cancer cell by MTT Assay.Methods: To evaluate the anticancer activity of SGLT2 inhibitors MTT Cytotoxic assay is performed as per standard protocols. Cancer cells were plated in 24-well plates and incubated at 370C with 5% CO2 condition. After convergence, samples are added to the plates in various concentrations and allowed to incubate then they are detached from the plates and cleansed with the reagents. The wells are coated with the dye and incubated. Later samples are analysed in UV-spectrophotometer.Results: Cytotoxic assay showed decrease in cell viability with increasing dose of SGLT2 inhibitors. IC50 values were determined graphically. The IC50 value of dapagliflozin is 400µg/ml and canagliflozin is 250µg/ml respectively after 24 hours of Assessment.Conclusions: The results of the current study give us an evidence that SGLT2 inhibitors dapagliflozin and canagliflozin exhibits anticancer property in Oral Cancer cell line.


2020 ◽  
Author(s):  
M. AYDIN AKBUDAK ◽  
Tevhide SUT ◽  
Nuraniye ERUYGUR ◽  
Ersin AKINCI

The Epilobium species are rich in various active phytochemicals and have seen wide use in folk medicine to treat several diseases, including benign prostatic hyperplasia. Although their benefits have been demonstrated on certain types of cancer cells, such as prostate cancer cells, their potential antiproliferative effects on colorectal adenocarcinoma cells have yet to be studied. The present study exhibited the antiproliferative activity of aqueous and ethanolic Epilobium parviflorum extracts in a colon cancer cell line, HT-29 cells in vitro. Both types of extracts reduced the cell viability of HT-29 cells in a dose-dependent manner. A gene expression analysis of the HT-29 cells demonstrated an increase in apoptotic genes, Caspase-3 and Caspase-8. Nuclear fragmentation of the apoptotic cells was also demonstrated through TUNEL assay and immunostaining experiments. On the other hand, the same lethal concentrations of the E. parviflorum extracts did not significantly affect a non-cancerous human fibroblast cell line, BJ cells. Our results confirmed that aqueous and ethanolic Epilobium parviflorum extracts can eliminate proliferation of human colorectal carcinoma cells in vitro. E. parviflorum may have the potential to become a therapeutic agent against colon cancers.


2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.


2019 ◽  
Vol 16 (5) ◽  
pp. 522-532 ◽  
Author(s):  
Bedia Kocyigit-Kaymakcioglu ◽  
Senem Sinem Yazici ◽  
Fatih Tok ◽  
Miriş Dikmen ◽  
Selin Engür ◽  
...  

Background: Hydrazones, one of the important classes of organic molecules, are pharmaceutical agents comprising –CO-NH-N=CH- group in the structure therefore and exhibiting significant biological activity. Methods: 5-Chloro-N’-[(substituted)methylidene] pyrazine-2-carbohydrazide (3a-g) and their Pd(II) complexes (4a-h) were synthesized and investigated in vitro anticancer activity on A549, Caco2 cancer and normal 3T3 fibroblast cell lines, using the MTT assay. Results: Anticancer activity screening results revealed that some compounds showed remarkable cytotoxic effect. Among them, 5-chloro-N'-[(4-hydroxyphenyl)methylidene] pyrazine-2-carbohydrazide (3c) displayed higher cytotoxic activity against A549 cancer cell line than the reference drug cisplatin. Conclusion: Compound 3c showed high cytotoxic activity against A549 cancer cell line but it showed low cytotoxic effect against normal 3T3 fibroblast cell line. Antiproliferative and antimetastatic effects of 3c were determined by the real-time monitoring of cell proliferative system (RTCA DP). The cell proliferation, metastatic and invasive activities of A549 cells were decreased due to increased concentration of 3c.


2020 ◽  
Vol 19 (18) ◽  
pp. 2223-2230 ◽  
Author(s):  
Poonam Verma ◽  
Sanjukta Naik ◽  
Pranati Nanda ◽  
Silvi Banerjee ◽  
Satyanarayan Naik ◽  
...  

Background: Coconut oil is an edible oil obtained from fresh, mature coconut kernels. Few studies have reported the anticancer role of coconut oil. The fatty acid component of coconut oil directly targets the liver by portal circulation and as chylomicron via lymph. However, the anti-cancer activity of coconut oil against liver cancer cells and oral cancer cells is yet to be tested. The active component of coconut oil, that is responsible for the anticancer activity is not well understood. In this study, three different coconut oils, Virgin Coconut Oil (VCO), Processed Coconut Oil (PCO) and Fractionated Coconut Oil (FCO), were used. Objective: Based on previous studies, it can be hypothesized that fatty acids in coconut oil may have anticancer potential and may trigger cell death in cancer cell lines. Methods: Each cell line was treated with different concentrations of Virgin Coconut Oil (VCO), Processed Coconut Oil (PCO) and Fractionated Coconut Oil (FCO). The treated cells were assayed by MTT after 72 hr of incubation. The fatty acid composition of different coconut oils was analyzed by gas chromatography. Result: Different concentrations of coconut oils were used to treat the cells. Interestingly, the anticancer efficacy of VCO, PCO and FCO was not uniform, rather the efficacy varied from cell line to cell line. Only 20% VCO showed significant anticancer activity in HepG2 cells in comparison to 80% PCO against the KB cell line. Remarkably, 20% of PCO and 5% of FCO showed potential growth inhibition in the KB cell line as compared to 80% PCO in HepG2 cells. Moreover, there was a difference in the efficacy of VCO, PCO and FCO, which might be due to their fatty acid composition. Comparing the anticancer efficacy of VCO, PCO and FCO in this study helped to predict which class of fatty acids and which fatty acid might be associated with the anticancer activity of VCO. Conclusion: This study shows that VCO, PCO and FCO have anticancer efficacy and may be used for the treatment of cancer, especially liver and oral cancer.


Author(s):  
Abdel Qader Al Bawab ◽  
Malek Zihlif ◽  
Yazan Jarrar ◽  
Ahmad Saleh

Background: Hypoxia (deprived oxygen in tissues) may induce molecular and genetic changes in cancer cells. Objective: Investigating the genetic changes of glucose metabolism in breast cancer cell line (MCF7) after exposure to continuous hypoxia (10 and 20 cycles exposure of 72 hours continuously on a weekly basis). Method: Gene expression of MCF7 cells was evaluated using real-time polymerase chain reaction- array method. Furthermore, cell migration and wound healing assays were also applied. Results: It was found that 10 episodes of continuous hypoxia activated Warburg effect in MCF7 cells via the significant up-regulation of genes involved in glycolysis (ANOVA, p value < 0.05). The molecular changes were associated with the ability of MCF7 cells to divide and migrate. Interestingly, after 20 episodes of continuous hypoxia, the expression glycolysis mediated genes has dropped significantly (from 30 to 9 folds). This could be attributed to the adaptive ability of cancer cells. Conclusion: It is concluded that 10 hypoxic episodes increased the survival rate and the aggressiveness of MCF7 cells and induced Warburg effect by up-regulation of the glycolysis mediating genes expression.


2021 ◽  
Vol 22 (14) ◽  
pp. 7698
Author(s):  
Sara Peri ◽  
Alessio Biagioni ◽  
Giampaolo Versienti ◽  
Elena Andreucci ◽  
Fabio Staderini ◽  
...  

Chemotherapy is still widely used as a coadjutant in gastric cancer when surgery is not possible or in presence of metastasis. During tumor evolution, gatekeeper mutations provide a selective growth advantage to a subpopulation of cancer cells that become resistant to chemotherapy. When this phenomenon happens, patients experience tumor recurrence and treatment failure. Even if many chemoresistance mechanisms are known, such as expression of ATP-binding cassette (ABC) transporters, aldehyde dehydrogenase (ALDH1) activity and activation of peculiar intracellular signaling pathways, a common and universal marker for chemoresistant cancer cells has not been identified yet. In this study we subjected the gastric cancer cell line AGS to chronic exposure of 5-fluorouracil, cisplatin or paclitaxel, thus selecting cell subpopulations showing resistance to the different drugs. Such cells showed biological changes; among them, we observed that the acquired chemoresistance to 5-fluorouracil induced an endothelial-like phenotype and increased the capacity to form vessel-like structures. We identified the upregulation of thymidine phosphorylase (TYMP), which is one of the most commonly reported mutated genes leading to 5-fluorouracil resistance, as the cause of such enhanced vasculogenic ability.


2021 ◽  
pp. 1-7
Author(s):  
Prihantono Prihantono ◽  
Rizal Irfandi ◽  
Indah Raya

BACKGROUND: With essential metals being studied and developed as anticancer agents, this study aims to explore the anticancer activity of Zn(II) arginine dithiocarbamate in the T47D and fibroblast cell lines. METHOD: The Zn(II) arginine dithiocarbamate complex was prepared by the in situ method and characterized using infra-red spectroscopy, melting point, X-ray fluorescence, and X-ray diffraction instruments. The complex compound was tested for its cytotoxicity to the T47D breast cancer and fibroblast cell lines. RESULTS: The cytotoxicity of the Zn(II) arginine dithiocarbamate complex to the T47D breast cancer cell line obtained IC50 = 3.16 μg/mL, while cisplatin obtained IC50 = 28.18 μg/mL. The cytotoxicity of the Zn(II) arginine dithiocarbamate complex to fibroblast cells obtained IC50 = 8709.63 μg/mL. CONCLUSION: The Zn(II) arginine dithiocarbamate complex has increased active cytotoxicity compared to cisplatin in inducing morphological changes in the T47D breast cancer cell line and is relatively non-toxic to fibroblast cells.


2021 ◽  
Vol 17 ◽  
pp. 174480692110240
Author(s):  
Silvia Gutierrez ◽  
James C Eisenach ◽  
M Danilo Boada

Some types of cancer are commonly associated with intense pain even at the early stages of the disease. The mandible is particularly vulnerable to metastasis from breast cancer, and this process has been studied using a bioluminescent human breast cancer cell line (MDA-MB-231LUC+). Using this cell line and anatomic and neurophysiologic methods in the trigeminal ganglion (TG), we examined the impact of cancer seeding in the mandible on behavioral evidence of hypersensitivity and on trigeminal sensory neurons. Growth of cancer cells seeded to the mandible after arterial injection of the breast cancer cell line in Foxn1 animals (allogeneic model) induced behavioral hypersensitivity to mechanical stimulation of the whisker pad and desensitization of tactile and sensitization of nociceptive mechanically sensitive afferents. These changes were not restricted to the site of metastasis but extended to sensory afferents in all three divisions of the TG, accompanied by widespread overexpression of substance P and CGRP in neurons through the ganglion. Subcutaneous injection of supernatant from the MDA-MB-231LUC+ cell culture in normal animals mimicked some of the changes in mechanically responsive afferents observed with mandibular metastasis. We conclude that released products from these cancer cells in the mandible are critical for the development of cancer-induced pain and that the overall response of the system greatly surpasses these local effects, consistent with the widespread distribution of pain in patients. The mechanisms of neuronal plasticity likely occur in the TG itself and are not restricted to afferents exposed to the metastatic cancer microenvironment.


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