Targeting the pentose phosphate pathway increases reactive oxygen species and induces apoptosis in thyroid cancer cells

Background: The sesquiterpene lactone cynaropicrin, a major constituent of the artichoke leaves extracts, has shown several biologic activities in many preclinical experimental models, including anti-proliferative effects. Objective: Herein we evaluated the effects of cynaropicrin on the growth of three human anaplastic thyroid carcinoma cell lines, investigating the molecular mechanism underlying its action. Method: MTT assay was used to evaluate the viability of CAL-62, 8505C and SW1736 cells, and flow cytometry to analyse cell cycle distribution. Western blot was performed to detect the levels of STAT3 phosphorylation and NFkB activation. Antioxidant effects were analyzed by measuring the reactive oxygen species and malonyldialdehyde dosage was used to check the presence of lipid peroxidation. Results: Viability of CAL-62, 8505C and SW1736 cells was significantly reduced by cynaropicrin in a dose- and time-dependent way, with an EC50 of about 5 µM observed after 48 h of treatment with the compound. Cellular growth inhibition was accompanied both by an arrest of the cell cycle, mainly in the G2/M phase, and the presence of a significant percentage of necrotic cells. After 48 h of treatment with 10 µM of cynaropicrin, a reduced nuclear expression of NFkB and STAT3 phosphorylation were also revealed. Moreover, we observed an increase in lipid peroxidation, without any significant effect on the reactive oxygen species production. Conclusion: These results demonstrate that cynaropicrin reduces the viability and promotes cytotoxic effects in anaplastic thyroid cancer cells associated with reduced NFkB expression, STAT3 phosphorylation and increased lipid peroxidation. Further characterization of the properties of this natural compound may open the way for using cynaropicrin as an adjuvant in the treatment of thyroid cancer.

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Selenite Induces Cell Cycle Arrest and Apoptosis via Reactive Oxygen Species-Dependent Inhibition of the AKT/mTOR Pathway in Thyroid Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.668424 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhen Cheng ◽

Shuang Yu ◽

Weiman He ◽

Jie Li ◽

Tianyi Xu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Cycle ◽

Thyroid Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Sodium Selenite ◽

Oxygen Species ◽

Cycle Arrest ◽

Intracellular Ros ◽

Thyroid Cancer Cells

Thyroid cancer is the most common endocrine malignancy, and its incidence has increased in the past decades. Selenium has been shown to have therapeutic effects against several tumors. However, its role in thyroid cancer and its underlying molecular mechanism remains to be explored. In the present study, we demonstrated that sodium selenite significantly decreased cell viability and induced G0/G1 cell cycle arrest and apoptosis in thyroid cancer cells in a dose-dependent manner. Transcriptomics revealed that sodium selenite induced intracellular reactive oxygen species (ROS) by promoting oxidative phosphorylation. Increased intracellular ROS levels inhibited the AKT/mTOR signaling pathway and upregulated EIF4EBP3. Intracellular ROS inhibition by N-acetylcysteine (NAC) ameliorated the cellular effects of sodium selenite. The in vitro findings were reproduced in xenograft thyroid tumor models. Our data demonstrated that sodium selenite exhibits strong anticancer effects against thyroid cancer cells, which involved ROS-mediated inhibition of the AKT/mTOR pathway. This suggests that sodium selenite may serve as a therapeutic option for advanced thyroid cancer.

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Targeting the pentose phosphate pathway in thyroid cancer cells

Endocrine Abstracts ◽

10.1530/endoabs.63.p382 ◽

2019 ◽

Author(s):

Shih-Ping Cheng ◽

Chien-Liang Liu ◽

Jie-Jen Lee ◽

Yi-Chiung Hsu ◽

Shih-Yuan Huang

Keyword(s):

Thyroid Cancer ◽

Cancer Cells ◽

Pentose Phosphate Pathway ◽

Pentose Phosphate ◽

Thyroid Cancer Cells

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Sustained oxidative stress instigates differentiation of cancer stem cells into tumor endothelial cells: Pentose phosphate pathway, reactive oxygen species and autophagy crosstalk

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.111643 ◽

2021 ◽

Vol 139 ◽

pp. 111643

Author(s):

Zahra Ghanbari Movahed ◽

Reza Yarani ◽

Parisa Mohammadi ◽

Kamran Mansouri

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Stem Cells ◽

Endothelial Cells ◽

Cancer Stem Cells ◽

Pentose Phosphate Pathway ◽

Reactive Oxygen ◽

Pentose Phosphate ◽

Oxygen Species ◽

Tumor Endothelial Cells

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Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species

Molecules ◽

10.3390/molecules25051229 ◽

2020 ◽

Vol 25 (5) ◽

pp. 1229

Author(s):

Abdul Q. Khan ◽

Elham A. N. Mohamed ◽

Ishrat Hakeem ◽

Aneeza Nazeer ◽

Shilpa Kuttikrishnan ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Therapeutic Potential ◽

Reactive Oxygen ◽

Dependent Manner ◽

Oxygen Species ◽

Papillary Thyroid ◽

Anticancer Effects ◽

Thyroid Cancer Cells

Sanguinarine (SNG), a natural compound with an array of pharmacological activities, has promising therapeutic potential against a number of pathological conditions, including malignancies. In the present study, we have investigated the antiproliferative potential of SNG against two well-characterized papillary thyroid cancer (PTC) cell lines, BCPAP and TPC-1. SNG significantly inhibited cell proliferation of PTC cells in a dose and time-dependent manner. Western blot analysis revealed that SNG markedly attenuated deregulated expression of p-STAT3, without affecting total STAT3, and inhibited growth of PTC via activation of apoptotic and autophagy signaling cascade, as SNG treatment of PTC cells led to the activation of caspase-3 and caspase-8; cleavage of PARP and activation of autophagy markers. Further, SNG-mediated anticancer effects in PTC cells involved the generation of reactive oxygen species (ROS) as N-acetyl cysteine (NAC), an inhibitor of ROS, prevented SNG-mediated antiproliferative, apoptosis and autophagy inducing action. Interestingly, SNG also sensitized PTC cells to chemotherapeutic drug cisplatin, which was inhibited by NAC. Finally, SNG suppressed the growth of PTC thyrospheres and downregulated stemness markers ALDH2 and SOX2. Altogether, the findings of the current study suggest that SNG has anticancer potential against PTC cells as well its derived cancer stem-like cells, most likely via inactivation of STAT3 and its associated signaling molecules.

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Correlation of Reactive Oxygen Species Levels with Resveratrol Sensitivities of Anaplastic Thyroid Cancer Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/6235417 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Xu Zheng ◽

Bin Jia ◽

Xiao-Ting Tian ◽

Xue Song ◽

Mo-Li Wu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Thyroid Carcinoma ◽

Cancer Cells ◽

Reactive Oxygen ◽

Anaplastic Thyroid Cancer ◽

Anaplastic Thyroid Carcinoma ◽

Ros Generation ◽

Therapeutic Effects ◽

Oxygen Species ◽

Thyroid Cancer Cells

Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid malignancy without a reliable therapeutic agent. Resveratrol possesses cancer-suppressive effects, while its effect(s) on ATC cells remains unknown. Because oxidative damage caused by increased reactive oxygen species (ROS) is one of the therapeutic effects of anticancer drugs and oxidative stress-caused mitochondria swelling is observed in resveratrol-treated cancer cells, the oxidative statuses and their relevance with resveratrol sensitivities are elucidated using THJ-16T and THJ-11T ATC cells established from two human anaplastic thyroid carcinoma cases. The results revealed that resveratrol-treated THJ-16T rather than THJ-11T cells showed remarkable growth arrest and extensive apoptosis accompanied with the elevated ROS generation and the attenuated superoxide dismutase 2 (SOD2) and catalase (CAT) levels. Mitochondrial impairment and the enhanced caspase-9/caspase-3 activation are found only in resveratrol-sensitive THJ-16T cells. Treatment with the antioxidant N-acetylcysteine (NAC) partly attenuated resveratrol-induced ROS generation and apoptosis of THJ-16T cells. The levels of resveratrol metabolic enzymes (SULT1A1 and SULT1C2) in THJ-16T cells were lower than those in THJ-11T cells and therefore reversely related with resveratrol sensitivities of ATC cells. Our findings demonstrate the ability of resveratrol to increase ROS generation and oxidative-related cellular lesions in resveratrol-sensitive THJ-16T cells presumably through activating the ROS-mitochondrial signal pathway. The levels of SULTs and ROS may reflect the response manners of ATC cells to resveratrol.

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Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180209152215 ◽

2019 ◽

Vol 18 (9) ◽

pp. 1313-1322 ◽

Cited By ~ 5

Author(s):

Manjula Devi Ramamoorthy ◽

Ashok Kumar ◽

Mahesh Ayyavu ◽

Kannan Narayanan Dhiraviam

Keyword(s):

Prostate Cancer ◽

Reactive Oxygen Species ◽

Cell Cycle ◽

Membrane Potential ◽

Cancer Cells ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Reactive Oxygen ◽

Oxygen Species ◽

Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

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