Withaferin A-Caused Production of Intracellular Reactive Oxygen Species Modulates Apoptosis via PI3K/Akt and JNKinase in Rabbit Articular Chondrocytes

Yu, Seon‐Mi; Kim, Song Ja

doi:10.3346/jkms.2014.29.8.1042

Cited by 23 publications

(13 citation statements)

References 29 publications

(27 reference statements)

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“…The co-incubation of cells with WE extract and NAC, an established ROS scavenger, quenched the ROS generation induced by WE. This finding is in conformity with previous data that reported that NAC attenuates Withania -induced ROS production in several cell lines [ 32 , 36 , 37 , 38 ]. Co-incubation with o-Phe, an iron chelator that breaks Fenton reaction and stops ROS generation [ 39 ], attenuated ROS generation to a similar extent as NAC.…”

Section: Discussionsupporting

confidence: 94%

“…WE extract caused a dose-dependent ROS generation in Jurkat cells. This finding is in agreement with previous studies reporting the ROS-generating ability of a similar WE extract [ 32 ] and some of its components such as WFA [ 32 , 33 , 36 , 37 , 38 ]. ROS generation induced by WE extract reached a plateau after 6 h of incubation.…”

Section: Discussionsupporting

confidence: 93%

“…This suggests that the extract rapidly induces a pro-oxidative status in intoxicated cells. Similar results were obtained by Malik [ 32 ], who found a significant ROS increase following 1 to 3 h of exposure to WFA [ 38 ]. The co-incubation of cells with WE extract and NAC, an established ROS scavenger, quenched the ROS generation induced by WE.…”

Section: Discussionsupporting

confidence: 89%

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Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells

Turrini

Calcabrini

Sestili

et al. 2016

Toxins

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Cancer chemotherapy is characterized by an elevated intrinsic toxicity and the development of drug resistance. Thus, there is a compelling need for new intervention strategies with an improved therapeutic profile. Immunogenic cell death (ICD) represents an innovative anticancer strategy where dying cancer cells release damage-associated molecular patterns promoting tumor-specific immune responses. The roots of Withania somnifera (W. somnifera) are used in the Indian traditional medicine for their anti-inflammatory, immunomodulating, neuroprotective, and anticancer activities. The present study is designed to explore the antileukemic activity of the dimethyl sulfoxide extract obtained from the roots of W. somnifera (WE). We studied its cytostatic and cytotoxic activity, its ability to induce ICD, and its genotoxic potential on a human T-lymphoblastoid cell line by using different flow cytometric assays. Our results show that WE has a significant cytotoxic and cytostatic potential, and induces ICD. Its proapoptotic mechanism involves intracellular Ca2+ accumulation and the generation of reactive oxygen species. In our experimental conditions, the extract possesses a genotoxic potential. Since the use of Withania is suggested in different contexts including anti-infertility and osteoarthritis care, its genotoxicity should be carefully considered for an accurate assessment of its risk–benefit profile.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

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Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells

Turrini

Calcabrini

Sestili

et al. 2016

Toxins

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“…5). Previous studies have suggested that accumulation of ROS promotes p21 Waf1/Cip1 expression [47]. Therefore, our findings suggest that LYG-202 may induce G1/S phase cell cycle arrest via excessive generation of ROS.…”

Section: Discussionmentioning

confidence: 85%

LYG-202 exerts antitumor effect on PI3K/Akt signaling pathway in human breast cancer cells

et al. 2015

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In this study, we aimed to investigate the antitumor effect of LYG-202, a newly synthesized piperazine-substituted derivative of flavonoid on human breast cancer cells and illustrate the potential mechanisms. LYG-202 induced apoptosis in MCF-7, MDA-MB-231 and MDA-MB-435 cells. LYG-202 triggered the activation of mitochondrial apoptotic pathway through multiple steps: increasing Bax/Bcl-2 ratio, decreasing mitochondrial membrane potential (ΔΨ(m)), activating caspase-9 and caspase-3, inducing cleavage of poly(ADP-ribose) polymerase, cytochrome c release and apoptosis-inducing factor translocation. Furthermore, LYG-202 inhibited cell cycle progression at the G1/S transition via targeting Cyclin D, CDK4 and p21(Waf1/Cip1). Additionally, LYG-202 increased the generation of intracellular ROS. N-Acetyl cysteine, an antioxidant, reversed LYG-202-induced apoptosis suggesting that LYG-202 induces apoptosis by accelerating ROS generation. Further, we found that LYG-202 deactivated the PI3K/Akt pathway, activated Bad phosphorylation, increased Cyclin D and Bcl-xL expression, and inhibited NF-κB nuclear translocation. Activation of PI3K/Akt pathway by IGF-1 attenuated LYG-202-induced apoptosis and cell cycle arrest. Our in vivo study showed that LYG-202 exhibited a potential antitumor effect in nude mice inoculated with MCF-7 tumor through similar mechanisms identified in cultured cells. In summary, our results demonstrated that LYG-202 induced apoptosis and cell cycle arrest via targeting PI3K/Akt pathway, indicating that LYG-202 is a potential anticancer agent for breast cancer.

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“…However, the protective effect of LBP on chondrocytes has not yet been examined in detail and the underlying mechanisms are still indistinct. It is reported that reactive oxygen species (ROS) acted as signaling intermediates of intracellular signaling that participate in cartilage homeostasis maintenance [23,24]. Excessive ROS exposure would lead to disruption of cartilage homeostasis [25,26].…”

Section: Introductionmentioning

confidence: 99%

Lycium barbarum polysaccharides exert an antioxidative effect on rat chondrocytes by activating the nuclear factor (erythroid-derived 2)-like 2 signaling pathway

Zhu

et al. 2020

aoms

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Introduction: Oxidative stress is the main cause of osteoarthritis (OA). Lycium barbarum polysaccharides (LBP) have antioxidant properties. Thus, the potential effect of LBP on H 2 O 2-stimulated chondrocytes was examined. Material and methods: The cell viability was detected by CCK-8. The reactive oxygen species (ROS) production and apoptosis rates were determined by flow cytometric analysis. The DNA damage was detected by comet assay. Real-time polymerase chain reaction (qPCR) and Western blot assays were performed to examine the expression of histone 2A family member X (γH2AX), checkpoint kinase 1 (Chk1), poly ADP-ribose polymerase (PARP), cysteinyl aspartate specific proteinase (caspase)-3/8/9, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its antioxidant-response element (ARE) dependent factors including heme oxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO-1). Results: Compared to the H 2 O 2 group, LBP inhibited the ROS production and DNA damage caused by H 2 O 2 (p < 0.05), respectively. LBP inhibited the mRNA and protein expressions of γH2AX and Chk1 (p < 0.05). Meanwhile, LBP significantly decreased apoptosis (p < 0.05). And LBP inhibited the expression levels of PARP and Caspase-3/8/9 (p < 0.05). Moreover, LBP increased the expression of Nrf2, HO-1and NQO-1 (p < 0.05). Furthermore, the depletion of Nrf2 that mediated by RNA interference reversed the apoptosis and DNA damage inhibition effect of LBP (p < 0.05). Conclusions: LBP protected chondrocytes through inhibiting DNA damage and apoptosis caused by H 2 O 2 , in which the Nrf2/ARE signaling pathway played a positive role. It provided an inspiration for clinical applicationdeveloping LBP as a therapeutic agent and Nrf2 as a promising candidate.

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Withaferin A-Caused Production of Intracellular Reactive Oxygen Species Modulates Apoptosis via PI3K/Akt and JNKinase in Rabbit Articular Chondrocytes

Cited by 23 publications

References 29 publications

Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells

Withania somnifera Induces Cytotoxic and Cytostatic Effects on Human T Leukemia Cells

LYG-202 exerts antitumor effect on PI3K/Akt signaling pathway in human breast cancer cells

Lycium barbarum polysaccharides exert an antioxidative effect on rat chondrocytes by activating the nuclear factor (erythroid-derived 2)-like 2 signaling pathway

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