Reactive oxygen species contribute to oridonin-induced apoptosis and autophagy in human cervical carcinoma HeLa cells

Zhang, Yahong; Wu, Yingliang; Tashiro, Shin‐ichi; Onodera, Satoshi; Ikejima, Takashi

doi:10.1038/aps.2011.92

Cited by 68 publications

(55 citation statements)

References 36 publications

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“…Oridonin could markedly increase Bax expression in mitochondria, and decreased Bcl-2 expression in both the cytosol and mitochondria, while NAC effectively blocked these effects in HeLa cells or human laryngeal HEp-2 cells. 25,26) As an evolutionarily conserved catabolic process that maintains cellular homeostasis under stress conditions, the occurrence of autophagy is also close links between ROS. Some report showed that recombinant macrophage migration inhibitory factor (rMIF) could induce ROS production and autophagy formation in human hepatoma cell line HuH-7 cells, while autophagy induced by rMIF was inhibited in the presence of NAC.…”

Section: Discussionmentioning

confidence: 99%

Hydroxyl Radical (·OH) Played a Pivotal Role in Oridonin-Induced Apoptosis and Autophagy in Human Epidermoid Carcinoma A431 Cells

Fan

Song

et al. 2012

Biological & Pharmaceutical Bulletin

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Oridonin, a diterpenoid compound extracted and purified from Rabdosia rubescen, has been reported to induce tumor cell apoptosis through tyrosine kinase pathway. To further examine the mechanism of oridonin, we selected human epidermoid carcinoma A431 cell as a test object. Besides apoptosis, oridonin also induced A431 cell autophagy, and this autophagy antagonized apoptosis and played a protective role for A431 cells. Reactive oxygen species (ROS) played a pivotal role in induction of cytotoxicity. Therefore, a ROS scavenger, N-acetylcysteine (NAC) combined with oridonin was appiled. Results of morphologic observation, flow cytometric analysis and Western blot analysis showed that NAC could significantly reverse both ROS generation and down-regulation of mitochondrial membrane potential in oridonin treated cells. NAC inhibited oridonin induced apoptosis through both the intrinsic and extrinsic apoptotic pathways. NAC effectively inhibited both oridonin-induced apoptosis and autophagy by reducing intracellular oxidative stress. To further examine the mechanism of ROS, exogenous enzyme antioxidants (superoxide dismutase (SOD), catalase (CAT)) and non-enzyme antioxidants (glutathione (GSH)) were applied to detect the effect of oridonin on ROS generation. Only GSH exerted a similar role with NAC, suggesting that hydroxyl radical (·OH) played the major role in oridonin-induced cell death. Oridonin could decrease the GSH level in A431 cells in a dosedependent manner. In addition, after treatment with ·OH donor, Fenton reagent, the changes in A431cells were similar to the results of oridonin treatment. All the results proved that ·OH played the pivotal role in oridonin induced apoptosis and autophagy in A431 cells.Key words oridonin; apoptosis; autophagy; reactive oxygen species; hydroxyl radical Reactive oxygen species (ROS) include highly reactive hydroxyl radicals (OH·), superoxide anions (O 2− ), singlet oxygen ( 1 O 2 ), and hydrogen peroxide (H 2 O 2 ), which form as natural products of the normal cellular metabolism of oxygen. 1) They play critical roles in the determination of cell fate by eliciting a wide variety of cellular responses, such as proliferation, differentiation and apoptosis.2) Under normal conditions, having been balanced by cell's antioxidant defense systems, low levels of ROS play important roles in cell signaling. However, under environmental stress, extended high levels of ROS would cause severe damage to cellular organisms, including DNA, RNA or proteins, which eventually lead to cell death via either apoptotic or other mechanisms.3) In many reports, ROS may also act as intracellular messengers, which are induced by a range of stimuli and triggered apoptosis. In these conditions, ROS are also produced in cell organelles, especially mitochondria. During oxidative stress-induced cell death, ROS can target the mitochondrial membrane potential. 4)Apoptosis (type I cell death) is one type of programmed cell death in multicellular organisms, and apoptotic cells are characterized by a series of mo...

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Section: Discussionmentioning

confidence: 99%

Hydroxyl Radical (·OH) Played a Pivotal Role in Oridonin-Induced Apoptosis and Autophagy in Human Epidermoid Carcinoma A431 Cells

Fan

Song

et al. 2012

Biological & Pharmaceutical Bulletin

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“…Previous studies have presupposed that autophagy and apoptosis might be triggered by common upstream signals. On a molecular level, this means that the apoptotic and autophagic response mechanisms share common pathways that either link or polarize cellular responses (Maiuri et al 2007, Zhang et al 2011. ROS could induce mitochondrial damage; conversely, mitochondrial damage is also a major source of intracellular ROS.…”

Section: Figurementioning

confidence: 99%

Autophagy protects osteoblasts from advanced glycation end products-induced apoptosis through intracellular reactive oxygen species

Yang

Meng

Yang

2016

Journal of Molecular Endocrinology

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Patients with type II diabetes are susceptible to fracture; however, these patients typically have normal bone mineral density. Thus, such fractures cannot be entirely explained by advanced glycation end products (AGEs)-induced osteoblast apoptosis. Autophagy is a molecular process allowing cells to degrade unnecessary or dysfunctional cellular organelles, and closely interacts with apoptosis. The aim of this study was to determine whether autophagy participated in the pathology of AGEs-treated osteoblasts, and the possible mechanism of such an involvement. Osteoblastic MC3T3-E1 cells were used. Autophagy was evaluated by detecting the level of LC3 via western blotting and immunofluorescence. p62/SQSTM1 expression was also assessed by western blotting. The autophagy inducer rapamycin (RA) and the autophagy inhibitor 3-methyladenine were used to determine whether autophagy has effect on AGEs-induced apoptosis. N-Acetylcysteine (NAC), reactive oxygen species (ROS) inhibitor, was used to determine whether ROS and mitochondrial damage were involved in autophagy regulation. The results showed that the autophagy level was increased in MC3T3-E1 cells treated with AGEs, as represented by an increase in both the total LC3 level and the LC3II/LC3I ratio, as well as a decrease in p62/SQSTMI expression. Further inducing autophagy by RA attenuated AGEs-induced apoptosis. The antioxidant NAC suppresses AGEs-induced autophagy in osteoblastic MC3T3-E1 cells. These results demonstrate that autophagy participates in the pathology of AGEs-treated osteoblasts, and may play a protective role in AGEs-induced apoptosis in osteoblastic MC3T3-E1 cells. ROS and mitochondrial damage are essential in upregulating AGEs-induced autophagy.

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“…However, the precise mechanism by which these V-ATPase inhibitors mediate these effects remains to be elucidated. Depending on the surrounding cell environment, cells experience oxidative stress and cell death when the levels of reactive oxygen species (ROS) exceed the counter-regulatory antioxidant capacity of the cell (Martindale and Holbrook, 2002;Zhang et al, 2011;Kim et al, 2011). Therefore, in this study, we clarified whether the V-ATPase inhibitors bafilomycin A1 and concanamycin A induce ROS production in RAW 264 cells.…”

Section: Introductionmentioning

confidence: 98%

Increased production of reactive oxygen species by the vacuolar-type (H<sup>+</sup>)-ATPase inhibitors bafilomycin A1 and concanamycin A in RAW 264 cells

Yokomakura

Hong²,

Ohuchi³

et al. 2012

J. Toxicol. Sci.

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-Treatment of the mouse leukemic cell line RAW 264 with bafilomycin A1 or concanamycin A, inhibitors of vacuolar-type (H + )-ATPases (V-ATPases), significantly increased the production of reactive oxygen species (ROS) and decreased cell viability. These effects were significantly suppressed by the presence of N-acetyl cysteine (NAC), an ROS scavenger. si-RNA mediated knockdown of the gene for the c subunit of the V0 domain of V-ATPase also resulted in an increase in ROS production and a decrease in cell viability. These results suggest that decreased cellular V-ATPase activity decreases cell viability by increasing ROS production in RAW 264 cells.

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Reactive oxygen species contribute to oridonin-induced apoptosis and autophagy in human cervical carcinoma HeLa cells

Cited by 68 publications

References 36 publications

Hydroxyl Radical (·OH) Played a Pivotal Role in Oridonin-Induced Apoptosis and Autophagy in Human Epidermoid Carcinoma A431 Cells

Hydroxyl Radical (·OH) Played a Pivotal Role in Oridonin-Induced Apoptosis and Autophagy in Human Epidermoid Carcinoma A431 Cells

Autophagy protects osteoblasts from advanced glycation end products-induced apoptosis through intracellular reactive oxygen species

Increased production of reactive oxygen species by the vacuolar-type (H<sup>+</sup>)-ATPase inhibitors bafilomycin A1 and concanamycin A in RAW 264 cells

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