Plumbagin induces apoptosis via the p53 pathway and generation of reactive oxygen species in human osteosarcoma cells

Aim: To investigate the effect of ultrasound during the synthesis of ZnO nanoparticles (NPs) on their anticancer activity. Materials & methods: ZnO NPs were synthesized in the presence and absence of ultrasonic irradiation. Biological tests were performed on human osteosarcoma cancer cells (Saos-2). Results: The sono-synthesized sample indicated higher cytotoxicity than the conventional one. (IC50 = 16.48 ± 0.41 μg/ml for sonochemical ZnO; 26.96 ± 0.33 μg/ml for conventional ZnO). Both sonochemical and conventional samples acted like antioxidants and reduced intracellular reactive oxygen species level. This reduction was more significant in cells treated with the sono-synthesized sample. The sono-synthesized ZnO NPs showed more tumor selectivity than the conventional sample. Conclusion: Sono-synthesis of ZnO NPs by a bath sonicator could improve their anticancer activity.

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Deoxyelephantopin Induces Reactive Oxygen Species-Mediated Apoptosis and Autophagy in Human Osteosarcoma Cells

Cellular Physiology and Biochemistry ◽

10.1159/000479537 ◽

2017 ◽

Vol 42 (5) ◽

pp. 1812-1821 ◽

Cited By ~ 8

Author(s):

Jilong Zou ◽

Yan Zhang ◽

Jiabing Sun ◽

Xiaoyan Wang ◽

Hualei Tu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Viability ◽

Morphological Changes ◽

Reactive Oxygen ◽

Annexin V ◽

Underlying Mechanism ◽

Ros Generation ◽

Oxygen Species ◽

Osteosarcoma Cells ◽

Human Osteosarcoma Cells

Background/Aims: Osteosarcoma is the predominant form of primary bone malignancy. Although the combinational application of neoadjuvant chemotherapy and surgical resection significantly increases the survival rate, the therapeutic outcome remains unsatisfactory. Deoxyelephantopin (DET), an active ingredient of Elephantopus scaber, has been reported to have an anti-tumor effect in recent publications. This study aimed to investigate whether DET has antineoplastic effects on osteosarcoma cells and its underlying mechanism. Methods: Cell viability and morphological changes were assessed by MTT and Live/dead assays. Cell apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential were detected utilizing Annexin V-FITC/PI double staining, DCFH-DA and JC-1 probes, respectively. Autophagy was detected by mRFP-GFP-LC3 adenovirus transfection and western blot. Results: DET dose-dependently reduced the viability of osteosarcoma cells following the increase in intracellular ROS levels. Pretreatment with N-acetylcysteine (NAC) reversed this effect. Furthermore, DET induced mitochondrial apoptosis. Depolarized cells were increased, and apoptosis-related proteins, such as Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3 and cleaved ploy ADP-ribose polymerase, were activated. Additionally, we found that DET could induce autophagy in osteosarcoma cells, but autophagy inhibition did not affect the decrease in cell viability. Conclusion: DET induced apoptosis in osteosarcoma cells through ROS generation, mitochondrial dysfunction and caspase activation; in addition, autophagy was involved in the effects of DET on osteosarcoma cells.

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Phyllanthus urinariaInduces Apoptosis in Human Osteosarcoma 143B Cells via Activation of Fas/FasL- and Mitochondria-Mediated Pathways

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/925824 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Hsin-Yi Wu ◽

Tsu-Kung Lin ◽

Hsiao-Mei Kuo ◽

Ya-Ling Huang ◽

Chia-Wei Liou ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Oxygen Species ◽

Mitochondrial Reactive Oxygen Species ◽

Extrinsic Pathway ◽

Membrane Potential Change ◽

Therapeutic Modalities ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells ◽

Ligand Expression

Phyllanthus urinaria (P. urinaria), in this study, was used for the treatment of human osteosarcoma cells, which is one of the tough malignancies with few therapeutic modalities. Herein, we demonstrated thatP. urinariainhibited human osteosarcoma 143B cells growth through an apoptotic extrinsic pathway to activate Fas receptor/ligand expression. Both intracellular and mitochondrial reactive oxygen species were increased to lead to alterations of mitochondrial membrane permeability and Bcl-2 family including upregulation of Bid, tBid, and Bax and downregulation of Bcl-2.P. urinariatriggered an intrinsic pathway and amplified the caspase cascade to induce apoptosis of 143B cells. However, upregulation of both intracellular and mitochondrial reactive oxygen species and the sequential membrane potential change were less pronounced in the mitochondrial respiratory-defective 143Bρ0cells compared with the 143B cells. This study offers the evidence that mitochondria are essential for the anticancer mechanism induced byP. urinariathrough both extrinsic and intrinsic pathways.

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Parthenolide Induces Reactive Oxygen Species-Mediated Autophagic Cell Death in Human Osteosarcoma Cells

Cellular Physiology and Biochemistry ◽

10.1159/000452532 ◽

2016 ◽

Vol 40 (1-2) ◽

pp. 146-154 ◽

Cited By ~ 8

Author(s):

Chen Yang ◽

Qing Ou Yang ◽

Qing-Jie Kong ◽

Wen Yuan ◽

Yue-Ping Ou Yang

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Cancer Cells ◽

Reactive Oxygen ◽

Annexin V ◽

Pharmacological Action ◽

Autophagic Cell Death ◽

Oxygen Species ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells

Background and Aim: Osteosarcoma is a devastating tumor of bone, primarily affecting adolescents. Parthenolide, a naturally occurring small molecule that interferes with NF-κB signaling, has recently attracted considerable attention because of its pharmacological action involving anti-cancer effects. However, the mechanism of the cytotoxic effect exerted by parthenolide on tumor cells is not clearly defined today. Methods: In this study, the effects of parthenolide were evaluated and characterized in human osteosarcoma cancer cell. Cell viability was assessed by CCK-8. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Results: Our results suggest that parthenolide did not cause caspase-dependent cell death in osteosarcoma cancer cells, as indicated by the absence of significant early apoptosis as well as caspase-3 cleavage. Instead, parthenolide increased the autophagy and mitophagy, as characterized by increased PINK1 and Parkin translocation to mitochondria and enhanced autophagy proteins. The induction of autophagy by parthenolide was associated with the increase of reactive oxygen species (ROS). ROS antioxidants N-acetylcysteine (NAC) attenuated parthenolide-induced autophagy activity. Conclusions: Our findings unveil a novel mechanism of drug action by parthenolide in osteosarcoma cancer cells and suggest a potential value of treating osteosarcoma cancer through a caspase-independent autophagic cell death by ROS activation.

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