scholarly journals Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83

2020 ◽  
Vol 21 (15) ◽  
pp. 5533 ◽  
Author(s):  
Daniela Cerretani ◽  
Giulia Collodel ◽  
Antonella Brizzi ◽  
Anna Ida Fiaschi ◽  
Andrea Menchiari ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Cell Viability ◽  
Annexin V ◽  
Ascorbic Acid Content ◽  
Carcinoma Cells ◽  
Cytotoxic Effects ◽  
Adenocarcinoma Cells ◽  
Malondialdehyde Content ◽  
Ht 29 ◽  
In Cells

In this study, we investigated the effects of exposition to IC50 dose for 24 h of a new synthetic cannabinoid (CB83) and of phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on HT-29 colorectal carcinoma cells. Cell viability and proliferative activity evaluated using the MTT, lactate dehydrogenase (LDH), and CyQUANT assays showed that cell viability was significantly affected when CB83, THC, and CBD were administered to cells. The results obtained showed that the reduced glutathione/oxidized glutathione ratio was significantly reduced in the cells exposed to CBD and significantly increased in the cells treated with the CB83 when compared to the controls. CBD treatment causes a significant increase in malondialdehyde content. The catalase activity was significantly reduced in HT-29 cells after incubation with CB83, THC, and CBD. The activities of glutathione reductase and glutathione peroxidase were significantly increased in cells exposed to THC and significantly decreased in those treated with CBD. The ascorbic acid content was significantly reduced in cells exposed to CB83, THC, and CBD. The ultrastructural investigation by TEM highlighted a significantly increased percentage of cells apoptotic and necrotic after CB83 exposition. The Annexin V-Propidium Iodide assay showed a significantly increased percentage of cells apoptotic after CB83 exposition and necrotic cells after CBD and THC exposition. Our results proved that only CBD induced oxidative stress in HT-29 colorectal carcinoma cells via CB receptor-independent mechanisms and that CB83 caused a mainly CB2 receptor-mediated antiproliferative effect comparable to 5-Fuorouracil, which is still the mainstay drug in protocols for colorectal cancer.

scholarly journals Cattleianal and Cattleianone: Two New Meroterpenoids from Psidium cattleianum Leaves and Their Selective Antiproliferative Action against Human Carcinoma Cells

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2891
Author(s):  
Engy A. Mahrous ◽  
Ahmed M. Al-Abd ◽  
Maha M. Salama ◽  
Magda M. Fathy ◽  
Fathy M. Soliman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Annexin V ◽  
Carcinoma Cells ◽  
Cell Cycle Analysis ◽  
Breast Adenocarcinoma ◽  
Human Carcinoma ◽  
Psidium Cattleianum ◽  
Antiproliferative Action ◽  
Adenocarcinoma Cells ◽  
Ht 29

The Myrteacae family is known as a rich source of phloroglucinols, a group of secondary metabolites with notable biological activities. Leaves of Psidium cattleianum were extracted with chloroform: methanol 8:2 to target the isolation of phloroglucinol derivatives. Isolated compounds were characterized using different spectroscopic methods: nuclear magnetic resonance (NMR), ultra-violet (UV) and mass spectrometry (MS). Two new phloroglucinols were evaluated for cytotoxicity against a panel of six human cancer cell lines, namely colorectal adenocarcinoma cells (HT-29 and HCT-116); hepatocellular carcinoma cells (HepG-2); laryngeal carcinoma (Hep-2); breast adenocarcinoma cells (MCF7 and MDA-MB231), in addition to normal human melanocytes HFB-4. Additionally, cell cycle analysis and annexin-V/FITC-staining were used to gain insights into the mechanism of action of the isolated compounds. The new phloroglucinol meroterpenoids, designated cattleianal and cattleianone, showed selective antiproliferative action against HT-29 cells with IC50’s of 35.2 and 32.1 μM, respectively. Results obtained using cell cycle analysis and annexin-V/FITC-staining implicated both necrosis and apoptosis pathways in the selective cytotoxicity of cattleianal and cattleianone. Our findings suggest that both compounds are selective antiproliferative agents and support further mechanistic studies for phloroglucinol meroterpenoids as scaffolds for developing new selective chemotherapeutic agents.

scholarly journals Anthracycline-induced cytotoxicity in the GL261 glioma model system

2021 ◽  
Author(s):  
Amber M. Tavener ◽  
Megan C. Phelps ◽  
Richard L. Daniels
Keyword(s):  
Cell Viability ◽  
Tumor Cells ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Effects ◽  
High Concentrations ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Gl261 Glioma

AbstractGlioblastoma (GBM) is a lethal astrocyte-derived tumor that is currently treated with a multi-modal approach of surgical resection, radiotherapy, and temozolomide-based chemotherapy. Alternatives to current therapies are urgently needed as its prognosis remains poor. Anthracyclines are a class of compounds that show great potential as GBM chemotherapeutic agents and are widely used to treat solid tumors outside the central nervous system. Here we investigate the cytotoxic effects of doxorubicin and other anthracyclines on GL261 glioma tumor cells in anticipation of novel anthracycline-based CNS therapies. Three methods were used to quantify dose-dependent effects of anthracyclines on adherent GL261 tumor cells, a murine cell-based model of GBM. MTT assays quantified anthracycline effects on cell viability, comet assays examined doxorubicin genotoxicity, and flow cytometry with Annexin V/PI staining characterized doxorubicin-induced apoptosis and necrosis. Dose-dependent reductions in GL261 cell viability were found in cells treated with doxorubicin (EC50 = 4.9 μM), epirubicin (EC50 = 5.9 μM), and idarubicin (EC50 = 4.4 μM). Comet assays showed DNA damage following doxorubicin treatments, peaking at concentrations of 1.0 μM and declining after 25 μM. Lastly, flow cytometric analysis of doxorubicin-treated cells showed dose-dependent induction of apoptosis (EC50 = 5.2 μM). Together, these results characterized the cytotoxic effects of anthracyclines on GL261 glioma cells. We found dose-dependent apoptotic induction; however at high concentrations we find that cell death is likely necrotic. Our results support the continued exploration of anthracyclines as compounds with significant potential for improved GBM treatments.

Homoharringtonine Contributes to Imatinib Sensitivity by Blocking EphB4/RhoA Pathway in Ph+ Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4420-4420
Author(s):  
Liu Xiaoli ◽  
Bintao Huang ◽  
Qingfeng Du ◽  
Jinfang Zhang ◽  
Na Xu ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Viability ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Annexin V ◽  
Apoptosis Rate ◽  
Xenograft Models ◽  
Stimulation Of ◽  
In Cells

Abstract Abstract 4420 Objective: The purpose was to investigate the role of the EphB4 in imatinib (IM) resistance and the mechanism why the homoharringtonine (HHT)+IM regimen gained more treatment profits than simple HHT or IM treating myeloid leukemia. Method: The stable under-expressing EphB4 cells (K562-R-EphB4-sh) were obtained. The cell viability and IC50 under the incubation of IM or HHT+IM was tested by MTT. PE Annexin V apoptosis detected the apoptosis rate of K562-R cells. Subcutaneous K562 xenograft models were established. The activated signal proteins in cells and tissues such as RhoA, MEK and ERK were tested by Western blot. Result: K562-R-EphB4-sh cell and xenograft were sensitivity to IM. Activated RhoA was not involved in K562-R-EphB4-sh cell and xenograft tissue. But phosphorylation of MEK/ERK was overexpression in K562-R-EphB4-sh cell and tissue. The apoptosis rate reached 58.71 ± 2.39% with K562-R cell incubated with HHT+IM, which was higher to K562-R cell incubated with IM (P=0.002). IC50 of K562-R cell incubated by IM was 5.45 mg/L. But under the stimulation of HHT+IM, IC50 of K562-R decreased from 5.45 to 1.17 mg/L (P<0.001). K562-R xenograft volumes significantly decreased with IM+HHT treatment comparing with before treatment (1692.82 ± 317.14 mm3 versus 975.56 ± 132.42 mm3, P<0.001). HHT blocked the expressions of EphB4/RhoA in K562-R cell and xenograft, but HHT cannot down-regulate the expression of P- MEK/ERK. Conclusions: A new marker of IM resistance mediated by the activation of EphB4/RhoA pathway. HHT+IM regimen gained more treatment profits than simple HHT or IM treating myeloid leukemia by blocking EphB4/RhoA pathway in Ph+ myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Benzo(a)pyrene, an Active Product of Cigarette Smoke, Role in PLA2 Isoforms Activation in Colon Cancer

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 193s-193s
Author(s):  
S. Sharma ◽  
S. Yadav ◽  
S. Rana ◽  
P. Avti ◽  
K.L. Khanduja
Keyword(s):  
Colon Cancer ◽  
Cell Viability ◽  
Cigarette Smoke ◽  
Membrane Integrity ◽  
Annexin V ◽  
Cell Types ◽  
Ros Generation ◽  
Dependent Manner ◽  
Colon Cells ◽  
Ht 29

Background and aim: One of the active combustion product of cigarette smoke, Benzo[a]pyrenes, role in pulmonary cancer is clearly understood. However, its role in gastrointestinal cancer including colon cancer is not clearly understood. Methods: In this study, benzo(a)pyrenes was treated to colon cells to evaluate its role in cell viability, cellular ROS, and gene expression of various PLA2 isoforms was evaluated by FACS and PCR. The identified PLA2 was silenced at the gene level to evaluate its role in cell viability and ROS generation. Results: B(a)P treatment at 1 µg/mL for 48 h to HCT-15 male colon cells significantly reduced the cell viability without affecting HT-29 female colon cells. Higher doses and longer treatment duration with B(a)P showed that female colon cells were highly sensitive than male colon cells. Annexin-V/PI staining for preapoptotic detection showed that B(a)P treatment increased the apoptosis in both the cell types in a concentration and time-dependent manner. The cytosolic ROS (cROS) and superoxide radical (SOR) formation in the female colon cells was significantly higher than male colon cells unlike the mitochondrial ROS (mtROS) production which was significantly higher in male colon cells. Treatment with B(a)P significantly upregulated the IID and IVA PLA2 isoform groups in HCT-15 male colon cells, whereas IB was upregulated in HT-29 female colon cells among the various PLA2 isozyme gene studied (IB, IID, III, IVA, IVB, IVC, VI, X, aiPLA2 and iPLA2). Gene silencing experiments targeting PLA2 IID and IVA in the HCT-15 male colon cells and IB in HT-29 female colon cells showed no effect with B(a)P treatment on the cell proliferation, apoptosis, membrane integrity and free radicals (ROS, mtROS, and SOR) generation. Conclusion: Targeting specific PLA2 isozymes in a cell-specific manner abolished the B(a)P-induced PLA2-mediated oxidative damage–related signaling pathways.

scholarly journals Effects of Polar Steroids from the Starfish Patiria (=Asterina) pectinifera in Combination with X-Ray Radiation on Colony Formation and Apoptosis Induction of Human Colorectal Carcinoma Cells

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3154 ◽  
Author(s):  
Olesya S. Malyarenko ◽  
Timofey V. Malyarenko ◽  
Alla A. Kicha ◽  
Natalia V. Ivanchina ◽  
Svetlana P. Ermakova
Keyword(s):  
Colorectal Carcinoma ◽  
Colony Formation ◽  
Soft Agar ◽  
Carcinoma Cells ◽  
Rational Approach ◽  
Apoptosis Induction ◽  
Dna Comet Assay ◽  
X Ray ◽  
Asterina Pectinifera ◽  
Ht 29

Despite significant advances in the understanding, prevention, and treatment of cancer, the disease continues to affect millions of people worldwide. Chemoradiation therapy is a rational approach that has already proven beneficial for several malignancies. However, the existence of toxicity to normal tissue is a serious limitation of this treatment modality. The aim of the present study is to investigate the ability of polar steroids from starfish Patiria (=Asterina) pectinifera to enhance the efficacy of radiation therapy in colorectal carcinoma cells. The cytotoxic activity of polar steroids and X-ray radiation against DLD-1, HCT 116, and HT-29 cells was determined by an MTS assay. The effect of compounds, X-ray, and their combination on colony formation was studied using the soft agar method. The molecular mechanism of the radiosensitizing activity of asterosaponin P1 was elucidated by western blotting and the DNA comet assay. Polar steroids inhibited colony formation in the tested cells, and to a greater extent in HT-29 cells. Asterosaponin P1 enhanced the efficacy of radiation and, as a result, reduced the number and size of the colonies of colorectal cancer cells. The radiosensitizing activity of asterosaponin P1 was realized by apoptosis induction through the regulation of anti- and pro-apoptotic protein expression followed by caspase activation and DNA degradation.

scholarly journals High Concentrations of Aspartame Induce Pro-Angiogenic Effects in Ovo and Cytotoxic Effects in HT-29 Human Colorectal Carcinoma Cells

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3600 ◽  
Author(s):  
Anca Laura Maghiari ◽  
Dorina Coricovac ◽  
Iulia Andreea Pinzaru ◽  
Ioana Gabriela Macașoi ◽  
Iasmina Marcovici ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
In Vitro Cytotoxicity ◽  
Scientific Data ◽  
Carcinoma Cells ◽  
Artificial Sweetener ◽  
In Ovo ◽  
Human Colorectal Carcinoma ◽  
Ht 29

Aspartame (ASP), an artificial sweetener abundantly consumed in recent years in an array of dietary products, has raised some concerns in terms of toxicity, and it was even suggested a link with the risk of carcinogenesis (colorectal cancer), though the present scientific data are rather inconclusive. This study aims at investigating the potential role of aspartame in colorectal cancer by suggesting two experimental approaches: (i) an in vitro cytotoxicity screening in HT-29 human colorectal carcinoma cells based on cell viability (Alamar blue assay), cell morphology and cell migration (scratch assay) assessment and (ii) an in ovo evaluation in terms of angiogenic and irritant potential by means of the chorioallantoic membrane method (CAM). The in vitro results showed a dose-dependent cytotoxic effect, with a significant decrease of viable cells at the highest concentrations tested (15, 30 and 50 mM) and morphological cellular changes. In ovo, aspartame (15 and 30 mM) proved to have a pro-angiogenic effect and a weak irritant potential at the vascular level. These data suggest new directions of research regarding aspartame’s role in colorectal cancer.

Catechol cytotoxicity in vitro: Induction of glioblastoma cell death by apoptosis

2010 ◽  
Vol 29 (3) ◽  
pp. 199-212 ◽  
Author(s):  
DM de Oliveira ◽  
BPS Pitanga ◽  
MS Grangeiro ◽  
RMF Lima ◽  
MFD Costa ◽  
...  
Keyword(s):  
Cell Death ◽  
Morphological Changes ◽  
Public Health Problem ◽  
Annexin V ◽  
Toxic Effects ◽  
Cytotoxic Effects ◽  
The Central Nervous System ◽  
Hematopoietic Toxicity ◽  
In Cells

The exposure to benzene is a public health problem. Although the most well-known effect of benzene is hematopoietic toxicity, there is little information about the benzene and its metabolites effects on the central nervous system (CNS). This study examined the toxic effects of 1,2-dihydroxybenzene (catechol), a benzene metabolite, to human glioblastoma GL-15 cells. GL-15 cell cultures were used as a model to provide more information about the toxic effects of aromatic compounds to the CNS. Catechol induced time- and concentration-dependent cytotoxic effects. Morphological changes, such as the retraction of the cytoplasm and chromatin clumping, were seen in cells exposed to 200 μM catechol for 48 hours. In cells exposed to 600 μM catechol for 48 hours, 78.0% of them presented condensed nuclei, and the Comet assay showed DNA damage. The percentage of cells labeled with annexin V (apoptotic cells) was greater in the group exposed to catechol (20.7%) than in control cells (0.4%). Exposure to catechol at concentrations greater than 100 μM enhanced Bax levels, and a decrease in Bcl-2 level was observed after the exposure to 600 μM catechol for 48 hours. Furthermore, catechol depleted reduced glutathione. Hence, catechol induced cell death mainly by apoptosis.

Assessment of anti-cancer effects of koenimbine on colon cancer cells

2020 ◽  
Vol 28 (3) ◽  
pp. 185-190
Author(s):  
Maliheh Astaneh ◽  
Soudeh Ghafouri-Fard ◽  
Zahra Fazeli ◽  
Zahra Taherian-Esfahani ◽  
Sepideh Dashti ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Annexin V ◽  
Colon Cancer Cells ◽  
Cytotoxic Effects ◽  
Anti Cancer ◽  
Ht 29

BACKGROUND: Recent studies have highlighted the role of natural elements in reduction of cancer cell growth and apoptosis. Koenimbine, a natural product isolated from Murraya koenigii (L) Spreng is a substance with cytotoxic effects on cancer cells. AIM: The effects of koenimbine on HT-29 and SW48 colon cancer cells were evaluated by MTT and Annexin V assays. Expression levels of Wnt/β-catenin pathway genes were quantified by real time PCR. RESULTS: The IC50 values of koenimbine in HT-29 and SW48 was calculated to be 50 μg/ml based on the results of MTT assay. This value was 75 μg/ml in IEC-18 cells which were used as normal control. Annexin V assays revealed induction of cell apoptosis and necrosis in HT-29 and SW48 cells but not IEG18 cells by koenimbine. Koenimbin treatment resulted in significant down-regulation of CYCLD1 expression in SW48 cell line, but up-regulation of this gene in HT29 cell line. Expression of TBLR1, DKK1, GSK3B and β-catenin was significantly decreased after koenimbin treatment in HT-19 cell line. Moreover, expression of DKK1 and GSK3B was significantly decreased after koenimbin treatment in SW-40 cell line. TCF4 expression was not detected in any of cell lines either before or after treatment with koenimbin. CONCLUSION: The current in vitro study showed the cytotoxic effects of koenimbin on two colon cancer cell lines and the effects of this substance on expression of selected genes from Wnt-β catenin pathway. Future in vivo studies are needed before suggestion of this substance as an anti-cancer drug.

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