Trail sensitivity of nasopharyngeal cancer cells involves redox dependent upregulation of TMTC2 and its interaction with membrane caspase-3

Objective: To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)- Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown. Methods: Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying mechanisms were demonstrated at the cellular, molecular, and in vivo levels. Results: Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)- Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly (ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in the HepG2 nude mouse model. Conclusion: Pt(II)-Bpy is a potential candidate for cancer chemotherapy.

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Pyrrolizines as Potential Anticancer Agents: Design, Synthesis, Caspase-3 activation and Micronucleus (MN) Induction

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180409155520 ◽

2019 ◽

Vol 18 (15) ◽

pp. 2124-2130

Author(s):

Amany Belal

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Anticancer Agents ◽

Caspase 3 ◽

Assay Method ◽

Breast Adenocarcinoma ◽

Compound I ◽

Design Synthesis ◽

Ic50 Values ◽

New Compounds

Background: For further exploration of the promising pyrrolizine scaffold and in continuation of our previous work, that proved the potential anticancer activity of the hit compound I, a new series of pyrrolizines 2-5 and 7-9 were designed and synthesized. Methods: Structures of the new compounds were confirmed by IR, 1H-NMR, 13C-NMR and elemental analysis. Antitumor activity for the prepared compounds against human breast adenocarcinoma (MCF-7), liver (HEPG2) and colon (HCT116) cancer cell lines was evaluated using SRB assay method. Result: Compounds 2, 3 and 5 were the most potent on colon cancer cells, their IC50 values were less than 5 µM. Compounds 2, 3 and 8 were the most potent on liver cancer cells, their IC50 values were less than 10 µM. As for MCF7, compounds 2, 7, 8 and 9 were the most active with IC50 values less than 10 µM. We can conclude that combining pyrrolizine scaffold with urea gave abroad spectrum anticancer agent 2 against the three tested cell lines. Micronucleus assays showed that compounds 2, 3, 8 are mutagenic and can induce apoptosis. In addition, caspase-3 activation was evaluated and compound 2 showed increase in the level of caspase-3 (9 folds) followed by 3 (8.28 folds) then 8 (7.89 folds). Conclusion: The obtained results encourage considering these three compounds as novel anticancer prototypes.

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Elucidation of the Chemopreventive Role of Stigmasterol Against Jab1 in Gall Bladder Carcinoma

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190206124120 ◽

2019 ◽

Vol 19 (6) ◽

pp. 826-837 ◽

Cited By ~ 3

Author(s):

Pratibha Pandey ◽

Preeti Bajpai ◽

Mohammad H. Siddiqui ◽

Uzma Sayyed ◽

Rohit Tiwari ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Gall Bladder ◽

Cancer Cells ◽

Caspase 3 ◽

Annexin V ◽

Gall Bladder Cancer ◽

Apoptosis Induction ◽

Bladder Cancer Cells ◽

Hoechst Staining

Background:Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet.Objective:In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells.Methods:In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells.Results:Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis.Conclusion:Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.

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Light activation of cyclometalated ruthenium complexes drives towards caspase 3 dependent apoptosis in gastric cancer cells

Journal of Inorganic Biochemistry ◽

10.1016/j.jinorgbio.2020.111080 ◽

2020 ◽

Vol 208 ◽

pp. 111080 ◽

Cited By ~ 1

Author(s):

Jorge Andrés Solís-Ruiz ◽

Anaïs Barthe ◽

Gilles Riegel ◽

Rafael Omar Saavedra-Díaz ◽

Christian Gaiddon ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Caspase 3 ◽

Ruthenium Complexes ◽

Light Activation ◽

Gastric Cancer Cells

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Overexpression of ribophorin II is required for viability of nasopharyngeal cancer cells by regulating JAK1/STAT3 activation

Immunopharmacology and Immunotoxicology ◽

10.1080/08923973.2021.1942038 ◽

2021 ◽

pp. 1-7

Author(s):

Bin Wang ◽

Weiwei Liu ◽

Xue Jiang ◽

Jian Li ◽

Xiaodong Hu ◽

...

Keyword(s):

Cancer Cells ◽

Nasopharyngeal Cancer

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Caspase‐3‐mediated GSDME induced Pyroptosis in breast cancer cells through the ROS/JNK signalling pathway

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.16574 ◽

2021 ◽

Author(s):

Ziwen Zhang ◽

Han Zhang ◽

Dongbo Li ◽

Xiaoping Zhou ◽

Qi Qin ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Caspase 3 ◽

Signalling Pathway

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Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells

Cancer Cell International ◽

10.1186/s12935-021-01942-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dongxiao Jiang ◽

Shufei Ding ◽

Zhujun Mao ◽

Liyan You ◽

Yeping Ruan

Keyword(s):

Colon Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Caspase 3 ◽

Time Dependent ◽

Integrated Analysis ◽

Dependent Manner ◽

Colon Cancer Cells ◽

Dapi Staining ◽

Aloe Emodin

Abstract Background Colon cancer is a malignant gastrointestinal tumour with high incidence, mortality and metastasis rates worldwide. Aloe-emodin is a monomer compound derived from hydroxyanthraquinone. Aloe-emodin produces a wide range of antitumour effects and is produced by rhubarb, aloe and other herbs. However, the mechanism by which aloe-emodin influences colon cancer is still unclear. We hope these findings will lead to the development of a new therapeutic strategy for the treatment of colon cancer in the clinic. Methods We identified the overlapping targets of aloe-emodin and colon cancer and performed protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, we selected apoptosis pathways for experimental verification with cell viability, cell proliferation, caspase-3 activity, DAPI staining, cell cycle and western blotting analyses to evaluate the apoptotic effect of aloe-emodin on colon cancer cells. Results The MTT assay and cell colony formation assay showed that aloe-emodin inhibited cell proliferation. DAPI staining confirmed that aloe-emodin induced apoptosis. Aloe-emodin upregulated the protein level of Bax and decreased the expression of Bcl-2, which activates caspase-3 and caspase-9. Furthermore, the protein expression level of cytochrome C increased in a time-dependent manner in the cytoplasm but decreased in a time-dependent manner in the mitochondria. Conclusion These results indicate that aloe-emodin may induce the apoptosis of human colon cancer cells through mitochondria-related pathways.

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Oxidative Stress and Apoptotic Responses Elicited by Nostoc-Synthesized Silver Nanoparticles against Different Cancer Cell Lines

Cancers ◽

10.3390/cancers12082099 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2099 ◽

Cited By ~ 3

Author(s):

Reham Samir Hamida ◽

Gadah Albasher ◽

Mashael Mohammed Bin-Meferij

Keyword(s):

Oxidative Stress ◽

Silver Nanoparticles ◽

Cancer Cells ◽

Hepg2 Cells ◽

Caspase 3 ◽

Mammalian Target Of Rapamycin ◽

B Cell Lymphoma ◽

Phosphorylated Akt ◽

Hct 116 ◽

Mcf 7

Green nanoparticles represent a revolution in bionanotechnology, providing opportunities to fight life-threatening diseases, such as cancer, with less risk to the environment and to human health. Here, for the first time, we systematically investigated the anticancer activity and possible mechanism of novel silver nanoparticles (N-SNPs) synthesized by Nostoc Bahar M against the MCF-7 breast cancer cells, HCT-116 colorectal adenocarcinoma cells, and HepG2 liver cancer cells, using cell viability assays, morphological characterization with inverted light and transmission electron microscopy, antioxidants and enzymes (glutathione peroxidase (GPx), glutathione (GSH), adenosine triphosphatase (ATPase), and lactate dehydrogenase (LDH)), and western blotting (protein kinase B (Akt), phosphorylated-Akt (p-Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma 2 (Bcl-2), tumor suppressor (p53), and caspase 3). N-SNPs decreased the viability of MCF-7, HCT-116, and HepG2 cells, with half-maximal inhibitory concentrations of 54, 56, and 80 µg/mL, respectively. They also significantly increased LDH leakage, enhanced oxidative stress via effects on antioxidative markers, and caused metabolic stress by significantly decreasing ATPase levels. N-SNPs caused extensive ultrastructural alterations in cell and nuclear structures, as well as in various organelles. Furthermore, N-SNPs triggered apoptosis via the activation of caspase 3 and p53, and suppressed the mTOR signaling pathway via downregulating apoptosis-evading proteins in MCF-7, HCT-116, and HepG2 cells. Ultrastructural analysis, together with biochemical and molecular analyses, revealed that N-SNPs enhanced apoptosis via the induction of oxidative stress and/or through direct interactions with cellular structures in all tested cells. The cytotoxicity of Nostoc-mediated SNPs represents a new strategy for cancer treatment via targeting various cell death pathways. However, the potential of N-SNPs to be usable and biocompatible anticancer drug will depend on their toxicity against normal cells.

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