Cytotoxic amounts of cisplatin induce either checkpoint adaptation or apoptosis in a concentration-dependent manner in cancer cells

2016 ◽  
Vol 108 (5) ◽  
pp. 127-148 ◽  
Author(s):  
Lucy H. Swift ◽  
Roy M. Golsteyn
Keyword(s):  
Cancer Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Checkpoint Adaptation

scholarly journals Effect of Palmitic Acid on Exosome-Mediated Secretion and Invasive Motility in Prostate Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2722
Author(s):  
Ivan V. Maly ◽  
Wilma A. Hofmann
Keyword(s):  
Prostate Cancer ◽  
Palmitic Acid ◽  
Cancer Cells ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Concentration Dependent Manner ◽  
Fat Consumption ◽  
Progression Markers

High fat consumption can enhance metastasis and decrease survival in prostate cancer, but the picture remains incomplete on the epidemiological and cell-biological level, impeding progress toward individualized recommendations in the clinic. Recent work has highlighted the role of exosomes secreted by prostate cancer cells in the progression of the disease, particularly in metastatic invasion, and also the utility of targeting these extracellular vesicles for diagnostics, as carriers of disease progression markers. Here, we investigated the question of a potential impact of the chief nutritional saturated fatty acid on the exosome secretion. Palmitic acid decreased the secretion of exosomes in human prostate cancer cells in vitro in a concentration-dependent manner. At the same time, the content of some prospective metastatic markers in the secreted exosomal fraction was also reduced, as was the ability of the cells to invade across extracellular matrix barriers. While by themselves our in vitro results imply that on the cell level, palmitic acid may be beneficial vis-à-vis the course of the disease, they also suggest that, by virtue of the decreased biomarker secretion, palmitic acid has the potential to cause unjustified deprioritization of treatment in obese and lipidemic men.

scholarly journals Efficient Delivery of Therapeutic siRNA by Fe3O4 Magnetic Nanoparticles into Oral Cancer Cells

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 615 ◽  
Author(s):  
Lili Jin ◽  
Qiuyu Wang ◽  
Jiayu Chen ◽  
Zixiang Wang ◽  
Hongchuan Xin ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
B Cell Lymphoma ◽  
Cell Counting ◽  
Blue Staining ◽  
Dependent Manner ◽  
Electronic Microscopy ◽  
Concentration Dependent Manner ◽  
Efficient Delivery ◽  
Oral Cancer Cells

The incidence of oral cancer is increasing due to smoking, drinking, and human papillomavirus (HPV) infection, while the current treatments are not satisfactory. Small interfering RNA (siRNA)-based therapy has brought hope, but an efficient delivery system is still needed. Here, polyethyleneimine (PEI)-modified magnetic Fe3O4 nanoparticles were prepared for the delivery of therapeutic siRNAs targeting B-cell lymphoma-2 (BCL2) and Baculoviral IAP repeat-containing 5 (BIRC5) into Ca9-22 oral cancer cells. The cationic nanoparticles were characterized by transmission electronic microscopy (TEM), scanning electronic microscopy (SEM), dynamic light scattering (DLS), and vibrating sample magnetometer (VSM). By gel retardation assay, the nanoparticles were found to block siRNA in a concentration-dependent manner. The cellular uptake of the nanoparticle/siRNA complexes under a magnetic field was visualized by Perl’s Prussian blue staining and FAM labeling. High gene silencing efficiencies were determined by quantitative real-time PCR and western blotting. Furthermore, the nanoparticle-delivered siRNAs targeting BCL2 and BIRC5 were found to remarkably inhibit the viability and migration of Ca9-22 cells, by cell counting kit-8 assay and transwell assay. In this study, we have developed a novel siRNA-based therapeutic strategy targeting BCL2 and BIRC5 for oral cancer.

scholarly journals Toxicological Effects of Traumatic Acid and Selected Herbicides on Human Breast Cancer Cells: In Vitro Cytotoxicity Assessment of Analyzed Compounds

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1710 ◽  
Author(s):  
Agata Jabłońska-Trypuć ◽  
Urszula Wydro ◽  
Elżbieta Wołejko ◽  
Andrzej Butarewicz
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner ◽  
Food Contaminants ◽  
Food Ingredient ◽  
Concentration Dependent Manner ◽  
Traumatic Acid

The main consequence of herbicides use is the presence of their residues in food of plant origin. A growing body of evidence indicates that herbicides cause detrimental effects upon human health while demonstrating a direct link of pesticides exposure with the occurrence of human chronic diseases, including cancer. There is a pressing need to develop our knowledge regarding interactions of food contaminants and food components both in vitro and in vivo. Pesticides are highly undesirable food contaminants, and traumatic acid (TA) is a very beneficial food ingredient, therefore we decided to study if TA may act as a compound that delays the stimulatory effect of pesticides on breast cancer cells. To analyze the potential effects that selected herbicides (MCPA, mesotrione, bifenox and dichlobenil) may have upon cancerous cells, we conducted studies of the cytotoxicity of physiological concentrations of four pesticides and the mix of TA with tested herbicides in three different breast cancer cell lines (MCF-7, ZR-75-1 and MDA-MB-231) and one normal healthy breast cell line MCF-12A. Based on the obtained results we conclude that TA in a concentration-dependent manner might influence selected effects of the studied herbicides for particular cancer cells lines.

Mechanism of Cepharanthine Cytotoxicity in Human Ovarian Cancer Cells

Planta Medica ◽  
2018 ◽  
Vol 85 (01) ◽  
pp. 41-47 ◽  
Author(s):  
Vilawan Payon ◽  
Chanaporn Kongsaden ◽  
Wannarasmi Ketchart ◽  
Apiwat Mutirangura ◽  
Piyanuch Wonganan
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cell ◽  
Apoptotic Cell ◽  
Chemotherapeutic Agents ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ovarian Cancer Cell Lines ◽  
Underlying Mechanisms

AbstractCepharanthine (CEP), a medicinal product derived from Stephania cephalantha Hayata, possesses a potent cytotoxicity against several types of cancers. Recently, we have found that CEP could efficiently inhibit the growth of mutated p53 colon cancer cells, which are often resistant to commonly used chemotherapeutic agents. In this study, we evaluated the cytotoxic effect and the underlying mechanisms of CEP on both chemosensitive CaOV-3 and chemoresistant OVCAR-3 ovarian cancer cell lines. The present study demonstrated that CEP significantly inhibited the growth of CaOV-3 and OVCAR-3 cells in a time- and concentration-dependent manner. CEP arrested CaOV-3 and OVCAR-3 cells in the G1 phase and S phase of cell cycle, respectively. Western blot analysis demonstrated that CEP markedly increased the expression of p21Waf1 protein and decreased the expression of cyclins A and D proteins in both CaOV-3 and OVCAR-3 cells. Additionally, CEP triggered apoptotic cell death in OVCAR-3 cells. Taken together, the above results suggest that CEP is a promising anticancer drug for ovarian cancer.

scholarly journals Effect of thimerosal on Ca2+ movement and viability in human oral cancer cells

2009 ◽  
Vol 28 (5) ◽  
pp. 301-308 ◽  
Author(s):  
LN Kuo ◽  
CJ Huang ◽  
YC Fang ◽  
CC Huang ◽  
JL Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Phospholipase C ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Flow Cytometry Data ◽  
Entry Inhibitors ◽  
Oral Cancer Cells ◽  
Induced Apoptosis

The effect of thimerosal on cytosolic free Ca2+ concentrations ([Ca2+]i ) in human oral cancer cells (OC2) is unclear. This study explored whether thimerosal changed basal [Ca2+]i levels in suspended OC2 cells using fura-2. Thimerosal at concentrations between 1and 50 μM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca 2+. Thimerosal-induced Ca2+ influx was not blocked by L-type Ca2+ entry inhibitors and protein kinase C modulators (phorbol 12-myristate 13-acetate [PMA] and GF109203X). In Ca2+-free medium, 50 μM thimerosal failed to induce a [Ca2+]i rise after pretreatment with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Inhibition of phospholipase C with U73122 did not change thimerosal-induced [Ca2+]i rises. At concentrations between 5 and 10 μM, thimerosal killed cells in a concentration-dependent manner. The cytotoxic effect of 8 μM thimerosal was potentiated by prechelating cytosolic Ca2+ with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetate/acetomethyl (BAPTA/ AM). Flow cytometry data suggested that 1—7 μM thimerosal-induced apoptosis in a concentration-dependent manner. Collectively, in OC2 cells, thimerosal-induced [Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx through non—L-type Ca2+ channels. Thimerosal killed cells in a concentration-dependent manner through apoptosis.

scholarly journals Global transcriptome analysis reveals partial estrogen-like effects of karanjin in MCF-7 breast cancer cells

2021 ◽  
Author(s):  
Gaurav Bhatt ◽  
Akshita Gupta ◽  
Latha Rangan ◽  
Anil Mukund Limaye
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Biological Activities ◽  
Biological Effects ◽  
Dependent Manner ◽  
Cell Type ◽  
Concentration Dependent Manner ◽  
Mcf 7

Karanjin, an abundantly occurring furanoflavonoid in edible and non-edible legumes, exerts diverse biological effects in vivo, and in vitro. Its potential as an anticancer agent is also gaining traction following recent demonstrations of its anti-proliferative, cell cycle inhibitory, and pro-apoptotic effects. However, the universality of its anticancer potential is yet to be scrutinized, particularly so because flavonoids can act as selective estrogen receptor modulators (SERMs). Even the genomic correlates of its biological activities are yet to be examined in hormone responsive cells. This paper presents the early and direct transcriptomic footprint of 10 μM karanjin in MCF-7 breast cancer cells, using next generation sequencing technology (RNA-seq). We show that karanjin-modulated gene-expression repertoire is enriched in several hallmark gene sets, which include early estrogen-response, and G2/M checkpoint genes. Genes modulated by karanjin overlapped with those modulated by 1 nM 17β-estradiol (E2), or 1 μM tamoxifen. Karanjin altered the expression of selected estrogen-regulated genes in a cell-type, and concentration dependent manner. It downmodulated the expression of ERα protein in MCF-7 cells. Furthermore, ERα knockdown negatively impacted karanjins ability to modulate the expression of selected E2 target genes. Our data suggest that karanjin exerts its effects on ERα-positive breast cancer cells, at least in part, via ERα. The apparent SERM-like effects of karanjin pose a caveat to the anticancer potential of karanjin. In-depth studies on cell-type and concentration-dependent effects of karanjin may bring out its true potential in endocrine therapies.

scholarly journals Antiproliferation Activity and Mechanism of c9, t11, c15-CLNA and t9, t11, c15-CLNA from Lactobacillus plantarum ZS2058 on Colon Cancer Cells

2020 ◽  
Author(s):  
Qing Ren ◽  
Bo Yang ◽  
Guangzhen Zhu ◽  
Shunyu Wang ◽  
Chengli Fu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Lactobacillus Plantarum ◽  
Linolenic Acid ◽  
Antioxidant Defenses ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Alpha Linolenic Acid ◽  
Concentration Dependent Manner ◽  
Caspase 1

The probiotic bacterial strain Lactobacillus plantarum ZS2058 has been proved to manifest comprehensive functions, which were due to ability to synthesise conjugated fatty acids (CFAs). To investigate the specific functions of CFAs produced by this probiotic bacterium, α-linolenic acid was isomerized by Lactobacillus plantarum strain ZS2058, and two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated lipid peroxidation was related to the antiproliferation activity of CLNAs. Examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. And no sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first report showing the ability of CLNAs to activate antioxidant defenses resulting in pyroptosis.

scholarly journals A Novel Synthetic Dihydroindeno[1,2-b] Indole Derivative (LS-2-3j) Reverses ABCB1- and ABCG2-Mediated Multidrug Resistance in Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3264 ◽  
Author(s):  
Chao Guo ◽  
Fangyuan Liu ◽  
Jie Qi ◽  
Jiahui Ma ◽  
Shiqi Lin ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Protein Expression ◽  
Atpase Activity ◽  
Cancer Cells ◽  
Abc Transporter ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Expression Levels ◽  
Chemotherapy Drugs ◽  
Diphenyltetrazolium Bromide

10-oxo-5-(3-(pyrrolidin-1-yl) propyl)-5,10-dihydroindeno [1,2-b] indol-9-yl propionate (LS-2-3j) is a new chemically synthesized indole compound and some related analogues are known to be inhibitors (such as alectinib and Ko143) of ATP-binding cassette (ABC) transporters, especially the ABC transporter subfamily B member 1 (ABCB1) and the ABC transporter subfamily G member 2 (ABCG2). This study aimed to evaluate the multidrug resistance (MDR) reversal effects and associated mechanisms of LS-2-3j in drug-resistant cancer cells. The inhibition of cell proliferation in tested agents was evaluated by the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. Accumulation or efflux of chemotherapy drugs was analyzed by flow cytometry. The ATPase activity was measured using an ATPase activity assay kit. The mRNA transcripts and protein expression levels were detected by real-time PCR and Western blot, respectively. In this connection, LS-2-3j significantly enhanced the activity of chemotherapeutic drugs in MDR cells and could significantly increase the intracellular accumulation of doxorubicin (DOX) and mitoxantrone (MITX) by inhibiting the function of the efflux pumps in ABCB1- or ABCG2-overexpressing cells. Furthermore, reduced ATPase activity, mRNA transcription, and protein expression levels of ABCB1 and ABCG2 were observed in a concentration dependent manner in MDR cancer cells.

scholarly journals Essential Oil from Zingiber ottensii Induces Human Cervical Cancer Cell Apoptosis and Inhibits MAPK and PI3K/AKT Signaling Cascades

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1419
Author(s):  
Jirapak Ruttanapattanakul ◽  
Nitwara Wikan ◽  
Kittinan Chinda ◽  
Thanathorn Jearanaikulvanich ◽  
Napatsorn Krisanuruks ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Essential Oil ◽  
Western Blot ◽  
Cancer Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Growth And Survival ◽  
Anti Cancer ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer

Zingiber ottensii (ZO) is a local plant in Thailand and has been used as a Thai traditional therapy for many conditions. ZO has been reported to exhibit many pharmacological effects, including anti-cancer activity. Nevertheless, its anti-cancer effects explored at the signaling level have not been elucidated in cervical cancer, which is one of the leading causes of fatality in females. We discovered that the essential oil of ZO significantly increased the apoptosis of human cervical cancer cells (HeLa) after 24 h of treatment in a concentration-dependent manner. Our data also clearly demonstrated that ZO essential oil reduced IL-6 levels in the culture supernatants of the cancer cells. Moreover, Western blot analysis clearly verified that cells were induced to undergo apoptotic death via caspase activation upon treatment with ZO essential oil. Interestingly, immunofluorescence studies and Western blot analyses showed that ZO essential oil suppressed epidermal growth factor (EGF)-induced pAkt and pERK1/2 signaling pathway activation. Together, our study demonstrates that ZO essential oil can reduce the proliferation and survival signaling of HeLa cervical cancer cells. Our study provides convincing data that ZO essential oil suppresses the growth and survival of cervical cancer cells, and it may be a potential choice for developing an anti-cancer agent for treating certain cervical cancers.

scholarly journals Antiausterity Activity of Arctigenin Enantiomers: Importance of (2R,3R)-Absolute Configuration

2014 ◽  
Vol 9 (1) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Suresh Awale ◽  
Mamoru Kato ◽  
Dya Fita Dibwe ◽  
Feng Li ◽  
Chika Miyoshi ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Absolute Configuration ◽  
The Other ◽  
Dependent Manner ◽  
Meoh Extract ◽  
Concentration Dependent Manner ◽  
Akt Activation ◽  
Other Hand

From a MeOH extract of powdered roots of Wikstroema indica, six dibenzyl-γ-butyrolactone-type lignans with (2 S,3 S)-absolute configuration [(+)-arctigenin (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)-hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl-γ-butyrolactone-type lignans with (2 R,3 R)-absolute configuration [(-)-arctigenin (1), (-)-matairesinol (2), (-)-trachelogenin (3)] were isolated from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in nutrient-deprived medium (NDM), but none of the six lignans (1–6) with (2 S,3 S)-absolute configuration showed preferential cytotoxicity. On the other hand, three lignans (1*–3*) with (2 R,3 R)-absolute configuration exhibited preferential cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82, and 5.85 μM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin was evaluated against the activation of Akt, which is a key process in the tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*) strongly suppressed the activation of Akt. These results indicate that the (2 R,3 R)-absolute configuration of (-)-enantiomers should be required for the preferential cytotoxicity through the inhibition of Akt activation.

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