scholarly journals Chemopreventive Effects and Antioxidant Capacity of Combined Leaf Extracts of Sesamum angustifolium (Oliv.) Engl. and Hibiscus articulatus on Rhabdomyosarcoma

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Clayton E. Siamayuwa ◽  
Loveness K. Nyanga ◽  
Cathrine Chidewe

Sesamum angustifolium (Oliv.) Engl. and Hibiscus articulatus contain compounds that have antimutagenic properties. The rise in rhabdomyosarcoma in paediatrics and prognosis of the disease in infants compared to adults calls for newer, less toxic alternatives in treatment of the disease. The aim of this study was to determine the anticancer activity and antioxidant capacity of combined leaf extracts of Sesamum angustifolium (Oliv.) Engl. and Hibiscus articulatus (SAHA), against rhabdomyosarcoma (RMS) using rhabdomyosarcoma (RD) cell line and mouse (L20B) cell line. Cytotoxicity, morphology, apoptosis induction, and antioxidant capacity assays were done. Of the four solvents used for extraction, the dichloromethane SAHA extract was the most cytotoxic with IC50 of 106 μg/mL after doxorubicin, the reference anticancer drug with IC50 of 0.8 μg/mL. The SAHA extracts had a stronger cytotoxicity effect on the cancerous RD cells than on normal L20B cells. Morphological assessment showed untreated cells maintained their normal striated appearance of muscle cells whereas cells treated with doxorubicin or SAHA extracts exhibited cell shrinkage, loss of surface adherence, reduced cell density along with cell debris, which is a characteristic of apoptosis. Normal L20B cells when treated with doxorubicin or SAHA extracts, maintained their cell shape, and remained adherent to the surface. The apoptotic enzyme caspase-3 was induced in a concentration dependent manner upon treatment of the RD cells with SAHA extracts or doxorubicin. Induction of caspase-3 was ten times less in treated L20B cells compared to the RD cells. Low induction of caspase-9 enzyme was observed in both treated RD and L20B cells. Treatment of both RD and L20B cells with SAHA extracts or doxorubicin resulted in increased activity of peroxidase and reduction of oxidative stress. Results of the study show that the SAHA extracts are potential sources of compounds that may serve as useful agents for treatment of rhabdomyosarcoma.

2003 ◽  
Vol 104 (2) ◽  
pp. 171-179 ◽  
Author(s):  
Declan A. HEALY ◽  
R. William G. WATSON ◽  
Philip NEWSHOLME

We report here that monounsaturated fatty acids and polyunsaturated fatty acids (PUFAs) provoke the accumulation of neutral lipids and apoptosis in retinoic acid-treated HL-60 cells in a concentration- and time-dependent manner. The PUFAs (arachidonic acid, docosahexanoic acid and eicosapentaenoic acid) provoked higher levels of HL-60 apoptosis compared with the monounsaturated oleic acid or the saturated palmitic acid. Cell size and granularity were also altered by fatty acid treatment. The PUFA-induced apoptosis was correlated with increased activity of caspase 3 and caspase 9. Lipid peroxidation was also increased in the presence of PUFAs, but was not responsible for activating cell apoptosis. Lipid derived metabolites may be responsible for activation of caspases and induction of cell apoptosis.


2020 ◽  
Vol 10 (8) ◽  
pp. 1224-1229
Author(s):  
Shihong Yao ◽  
Pu Huang ◽  
Fen Liu ◽  
Fanyang Zeng ◽  
Wenxuan Zeng ◽  
...  

The aims of this work were to investigate the effect of a polymer-modified folate-targeted magnetic nano-delivery system on growth inhibition of CNE2 cells and expression of Caspase-3 mRNA, and Caspase-3, Caspase-8, and Caspase-9 proteins, and to explore the mechanism used by this nano-delivery system to inhibit proliferation and induce apoptosis of human nasopharyngeal carcinoma cells. The MTT method was used to detect the effect of the polymer-modified folate-targeted magnetic nano-delivery system at different concentrations (0, 0.25, 0.50, 0.75, 1.00, 1.50, 2.00 g/mL) on CNE2 cell proliferation; the fluorescence PCR method was used to detect changes in Caspase-3 mRNA at different concentrations (0, 0.75, 1.00, 1.50 g/mL); and western blotting was used to detect Caspase-3, Caspase-8, and Caspase-9 expression. The polymer-modified folate-targeted magnetic nanoparticles inhibited the expression of Caspase-3 mRNA, and of Caspase-3, Caspase-8, and Caspase-9 in CNE2 cells in a concentration-dependent manner. It may be concluded that the polymer-modified folate-targeted magnetic nano-delivery system can inhibit the growth of CNE2 cells and its effect is closely related to the upregulation of Caspase-3 mRNA and Caspase-3, Caspase-8, and Caspase-9 protein expression and initiation of the caspase cascade.


2020 ◽  
Vol 20 (6) ◽  
pp. 930-942 ◽  
Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Irfan A. Ansari

Background: In recent years, natural products have received great attention for cancer prevention owing to their various health benefits, noticeable lack of toxicity and side effects, and the limitations of chemotherapeutic agents. Andrographolide, a labdane diterpenoid is a principal bioactive constituent of Andrographis paniculata Nees, exhibits significant anticancer activity. Objective: The efficacy of andrographolide on colon cancer cells is yet to be elucidated completely. Therefore, we investigated the anticancer efficiency of andrographolide in colon cancer DLD1 cell line. Methods: Antiproliferative activity of andrographolide on DLD1 cells was evaluated by MTT assay, LDH release assay, morphological analysis and colony formation assay. Induction of apoptosis was determined by DAPI staining, Annexin V-FITC staining assay, and caspase-3 activation assay. Role of andrographolide induced cellular reactive oxygen species (ROS) and its association with apoptosis induction in DLD1 cells was elucidated by DCFDA dye. Synergistic ability of andrographolide with 5- fluorouracil (5-FU) and paclitaxel (PTX) was evaluated by MTT assay. Results: Results of the present study indicated that andrographolide declined cell viability of DLD1 cells in a concentration and time-dependent manner. Andrographolide induced apoptosis via nuclear condensation, phosphatidylserine externalization and caspase-3 activation. It also augmented cellular ROS levels which were in turn associated with apoptosis induction in DLD1 cells. Moreover, andrographolide displayed synergistic activity with 5-FU and PTX against DLD1 cells. Conclusion: The present study showed that andrographolide demonstrated antiproliferative and apoptotic properties, moreover it also displayed synergistic effect with chemotherapeutic drugs in colon cancer DLD1 cells.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Prisca Bustamante Alvarez ◽  
Alexander Laskaris ◽  
Alicia A. Goyeneche ◽  
Yunxi Chen ◽  
Carlos M. Telleria ◽  
...  

Abstract Background Uveal melanoma (UM), the most prevalent intraocular tumor in adults, is a highly metastatic and drug resistant lesion. Recent studies have demonstrated cytotoxic and anti-metastatic effects of the antiprogestin and antiglucocorticoid mifepristone (MF) in vitro and in clinical trials involving meningioma, colon, breast, and ovarian cancers. Drug repurposing is a cost-effective approach to bring approved drugs with good safety profiles to the clinic. This current study assessed the cytotoxic effects of MF in human UM cell lines of different genetic backgrounds. Methods The effects of incremental concentrations of MF (0, 5, 10, 20, or 40 μM) on a panel of human UM primary (MEL270, 92.1, MP41, and MP46) and metastatic (OMM2.5) cells were evaluated. Cells were incubated with MF for up to 72 h before subsequent assays were conducted. Cellular functionality and viability were assessed by Cell Counting Kit-8, trypan blue exclusion assay, and quantitative label-free IncuCyte live-cell analysis. Cell death was analyzed by binding of Annexin V-FITC and/or PI, caspase-3/7 activity, and DNA fragmentation. Additionally, the release of cell-free DNA was assessed by droplet digital PCR, while the expression of progesterone and glucocorticoid receptors was determined by quantitative real-time reverse transcriptase PCR. Results MF treatment reduced cellular proliferation and viability of all UM cell lines studied in a concentration-dependent manner. A reduction in cell growth was observed at lower concentrations of MF, with evidence of cell death at higher concentrations. A significant increase in Annexin V-FITC and PI double positive cells, caspase-3/7 activity, DNA fragmentation, and cell-free DNA release suggests potent cytotoxicity of MF. None of the tested human UM cells expressed the classical progesterone receptor in the absence or presence of MF treatment, suggesting a mechanism independent of the modulation of the cognate nuclear progesterone receptor. In turn, all cells expressed non-classical progesterone receptors and the glucocorticoid receptor. Conclusion This study demonstrates that MF impedes the proliferation of UM cells in a concentration-dependent manner. We report that MF treatment at lower concentrations results in cell growth arrest, while increasing the concentration leads to lethality. MF, which has a good safety profile, could be a reliable adjuvant of a repurposing therapy against UM.


2020 ◽  
Vol 10 (8) ◽  
pp. 2684
Author(s):  
María González-Locarno ◽  
Yarley Maza Pautt ◽  
Alberto Albis ◽  
Edwin Florez López ◽  
Carlos David Grande Tovar

Cape gooseberry (Physalis peruviana L.) is one of the main exotic fruits in demand throughout the world market. However, this fruit has problems with physical and microbial decay causing losses up to thirty percent during post-harvest stage and market storage. As an alternative for conservation, technologies based on edible coatings of biopolymers incorporating essential oils have been developed. In this paper we studied the effect of edible coatings based on chitosan (CS) and Ruta graveolens L. essential oil (RGEO) at different concentrations applied on the surface gooseberries at 18 ± 2 °C. The emulsions exhibited a reduction in the viscosity and the particle size with the increasing in the RGEO amount (from 124.7 cP to 26.0 cP for CS + RGEO 0.5% and CS + RGEO 1.5%, respectively). A lower weight loss was obtained for fruits coated with CS + RGEO 0.5% (12.7%) as compared to the uncoated (15%), while the maturity index increased in a lower amount for CS + RGEO coated than the uncoated fruits. The mesophyll growth was delayed three days after the coating applications for CS + RGEO 1.0% and 1.5%. At day twelve of the coating process, fruits with CS + RGEO 1.5% presented only 3.1 Log UFC/g of aerobic mesophylls and 2.9 Log UFC/g of molds and yeasts, while the uncoated fruits presented 4.2 Log UFC/g of aerobic mesophylls and 4.0 Log UFC/g of molds and yeasts, demonstrating a microbial barrier of the coatings incorporating RGEO in a concentration dependent manner. The CS + RGEO coating also preserve the antioxidant property of case gooseberries after twelve days of treatment under storage according to the 2,2′-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethyl-benzothiazoline-6-sulphonic acid) (ABTS) results. It was demonstrated by the ABTS method that T5 antioxidant capacity from day one to day twelve only decreases from 55% to 44%, while in the uncoated fruits (T1) the antioxidant capacity decreased from 65% to 18%. On the other hand, using the DPPH method the reduction was from 73% to 24% for the uncoated samples and 55% to 43% for T5. From the sensorial analysis, we recommend the use of CS + RGEO 0.5% that was still accepted by the panelists after the sixth day of application. These results show the potential application of these coatings as postharvest treatment under storage and low temperature conditions during twelve days of treatment for cape gooseberry fruits.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Christopher Platen ◽  
Stephan Dreschers ◽  
Jessica Wappler ◽  
Andreas Ludwig ◽  
Stefan Düsterhöft ◽  
...  

Neonates are extremely susceptible to bacterial infections, and evidences suggest that phagocytosis-induced cell death (PICD) is less frequently triggered in neonatal monocytes than in monocytes from adult donors. An insufficient termination of the inflammatory response, leading to a prolonged survival of neonatal monocytes with ongoing proinflammatory cytokine release, could be associated with the progression of various inflammatory diseases in neonates. Our previous data indicate that amphiregulin (AREG) is increasingly expressed on the cell surface of neonatal monocytes, resulting in remarkably higher soluble AREG levels after proteolytic shedding. In this study, we found that E. coli-infected neonatal monocytes show an increased phosphorylation of ERK, increased expression of Bcl-2 and Bcl-XL, and reduced levels of cleaved caspase-3 and caspase-9 compared to adult monocytes. In both cell types, additional stimulation with soluble AREG further increased ERK activation and expression of Bcl-2 and Bcl-XL and reduced levels of cleaved caspase-3 and caspase-9 in an EGFR-dependent manner. These data suggest that reduced PICD of neonatal monocytes could be due to reduced intrinsic apoptosis and that AREG can promote protection against PICD. This reduction of the intrinsic apoptosis pathway in neonatal monocytes could be relevant for severely prolonged inflammatory responses of neonates.


2008 ◽  
Vol 5 (2) ◽  
pp. 165-171 ◽  
Author(s):  
Sang Chan Kim ◽  
Sook Jahr Park ◽  
Jong Rok Lee ◽  
Jung Cheol Seo ◽  
Chae Ha Yang ◽  
...  

Licorice,Glycyrrhizae radix, is one of the herbal medicines in East Asia that has been commonly used for treating various diseases, including stomach disorders. This study investigated the effect of licorice on arsenite (As)-induced cytotoxicity in H4IIE cells, a rat hepatocyte-derived cell line. Cell viability was significantly diminished in As-treated H4IIE cells in a time and concentration-dependent manner. Furthermore, results from flow cytometric assay and DNA laddering in H4IIE cells showed that As treatment induced apoptotic cell death by activating caspase-3. Licorice (0.1 and 1.0 mg ml−1) treatment significantly inhibited cell death and the activity of caspase-3 in response to As exposure. These results demonstrate that licorice induced a cytoprotective effect against As-induced cell death by inhibition of caspase-3.


2005 ◽  
Vol 393 (1) ◽  
pp. 171-180 ◽  
Author(s):  
Mariko Omatsu-Kanbe ◽  
Kazuko Inoue ◽  
Yusuke Fujii ◽  
Takefumi Yamamoto ◽  
Takahiro Isono ◽  
...  

The effect of extracellular ATP on adipogenesis was investigated using the mouse 3T3-L1 cell line. Incubation of cells with ATP (1–100 μM) for 5 min induced actin filament reorganization and membrane ruffling mediated through P2Y receptors. Enhancement of preadipocyte migration into fat cell clusters is one of the essential processes of adipose tissue development in vivo and cell migration assays revealed that stimulation of P2Y receptors enhanced chemokinesis (migration) in a concentration dependent manner. In this cell line, growth arrest is required before initiation of differentiation and growth-arrested post-confluent cells can be converted into adipocytes by the presence of the adipogenic hormones dexamethasone, 3-isobutyl-1-methylxanthine and insulin. On the other hand, those hormones alone do not trigger differentiation in proliferating cells. ATP did not induce differentiation when applied alone to either proliferating or postconfluent cells. By contrast, proliferating cells (density <50%) preincubated with ATP for 5 min and subsequently given the adipogenic hormones in the continued presence of ATP, underwent adipocyte differentiation mediated through phospholipase C-coupled P2Y receptors. These adipocytes were found to show very similar characteristics, including morphology and intracellular triacylglycerol accumulation compared with adipocytes differentiated from post-confluent preadipocytes with those adipogenic hormones. When proliferating cells were preincubated with ATP before the addition of the adipogenic hormones, gene expression of aP2 (adipose protein 2) was markedly increased within 6 days, whereas without ATP pretreatment the expression level stayed very low. These results suggest that extracellular ATP renders preadipocytes responsive to adipogenic hormones during the growth phase.


2018 ◽  
Vol 37 (12) ◽  
pp. 1293-1309 ◽  
Author(s):  
Y Xue ◽  
J Wang ◽  
Y Huang ◽  
X Gao ◽  
L Kong ◽  
...  

Silver nanoparticles are used in many commercial products in daily life. Exposure to nanosilver has hepatotoxic effects in animals. This study investigated the cytotoxicity associated with polyvinylpyrrolidone-coated nanosilver (23.44 ± 4.92 nm in diameter) exposure in the human hepatoma cell line (HepG2) and normal hepatic cell line (L02), and the molecular mechanisms induced by nanosilver in HepG2 cells. Nanosilver, in doses of 20–160 μg mL−1 for 24 and 48 h, reduced cell viability in a dose- and time-dependent manner and induced cell membrane leakage and mitochondria injury in both cell lines; these effects were more pronounced in HepG2 cells than in L02 cells. Intracellular oxidative stress was documented by reactive oxygen species (ROS) being generated in HepG2 cells but not in L02 cells, an effect possibly due to differential uptake of nanosilver by cancer cells and normal cells. In HepG2 cells, apoptosis was documented by finding that ROS triggered a decrease in mitochondrial membrane potential, an increase in cytochrome c release, activation of caspase 3 and caspase 9, and a decrease in the ratio of Bcl-2/Bax. Furthermore, nanosilver activated the Fas death receptor pathway by downregulation of nuclear factor-κB and activation of caspase 8 and caspase 3. These results suggest that apoptosis induced by nanosilver in HepG2 cells is mediated via a mitochondria-dependent pathway and the Fas death receptor pathway. These findings provide toxicological and mechanistic information that can help in assessing the effects of nanosilver in biological systems, including the potential for anticancer activities.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Dian-lei Wang ◽  
Chen-yin Wang ◽  
Yin Cao ◽  
Xian Zhang ◽  
Xiu-hua Tao ◽  
...  

Multidrug resistance-associated protein 1 (MRP1), a member of the ATP-binding cassette (ABC) superfamily of transporters, plays an important role in normal lung physiology by protecting cells against oxidative stress and toxic xenobiotics. The present study investigates the effects of allyl isothiocyanate (AITC) onMRP1mRNA and MRP1 protein expression and transporter activity in the immortalised human bronchial epithelial cell line 16HBE14o-.MRP1mRNA and MRP1 protein expression in 16HBE14o- cells that were treated with allyl isothiocyanate were analysed by real-time PCR assay and Western blotting. The transport of carboxyfluorescein, a known MRP1 substrate, was measured by functional flow cytometry to evaluate MRP1 activity. Treatment with AITC at concentrations of 5–40 μM increased MRP1 protein levels in a concentration-dependent manner. AITC treatments at concentrations of 1–40 μM caused concentration-dependent increases inMRP1mRNA levels that were up to seven times greater than the levels found in control cells. Finally, AITC treatment at concentrations of 5–40 μM significantly increased MRP1-dependent efflux in 16HBE14o- cells. These results suggest that AITC can increase the expression and activity of MRP1 in 16HBE14o- cells in a concentration-dependent manner. The upregulation of MRP1 activity and expression by AITC could produce therapeutic effects in the treatment of lung disease.


Sign in / Sign up

Export Citation Format

Share Document