Reactive oxygen species mediate oridonin-induced apoptosis through DNA damage response and activation of JNK pathway in diffuse large B cell lymphoma

Xu, Zhuang; Fu, Wanbin; Jin, Zhen; Guo, Peng; Wang, Wenfang; Jm, Li

doi:10.3109/10428194.2015.1061127

Cited by 24 publications

(18 citation statements)

References 33 publications

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“…Our previous studies have indicated that oridonin and NVP-BEZ235 have some antitumor effects in DLBCL cells [5, 6]. The aim of this study was to determine whether oridonin combined with NVP-BEZ235 could achieve a more significant antitumor effect on the non-GCB DLBCL, and to further investigate the underlying mechanism.…”

Section: Resultsmentioning

confidence: 98%

Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma

Qing

Jin

et al. 2016

J Hematol Oncol

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We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL) both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0303-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 98%

Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma

Qing

Jin

et al. 2016

J Hematol Oncol

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“…Oridonin, a diterpenoid isolated from medicinal herb Rabdosia rubescens , has been proved to possess potent antitumor effect on various cancers, such as colon cancer cells 28 , lymphoma cells 29 , breast cancer cells 30 and leukemia cells 31 . It has been documented that oridonin may induce apoptosis in numerous cancers 32 , 33 .…”

Section: Introductionmentioning

confidence: 99%

Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-γ and inhibiting Nrf2 pathway

et al. 2018

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Osteosarcoma is the most common high-grade human primary malignant bone sarcoma with lower survival in the past decades. Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens, has been proved to possess potent anti-cancer effects. However, its potential mechanism still remains not fully clear nowadays. In this study, we investigated the anticancer effect of oridonin on human osteosarcoma and illuminated the underlying mechanisms. In vitro, oridonin inhibited the cell viability of various osteosarcoma cells. We demonstrated that oridonin induced mitochondrial-mediated apoptosis by increasing Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (MMP), triggering reactive oxygen species (ROS) generation and activating caspase-3 and caspase-9 cleavage in MG-63 and HOS cells. Moreover, we found that oridonin triggered ROS by inhibiting NF-E2-related factor 2 (Nrf2) pathway and induced mitochondrial apoptosis via inhibiting nuclear factor-κB (NF-κB) activation by activating Peroxisome Proliferator-Activated Receptor γ (PPAR-γ) in MG-63 and HOS cells. We further confirmed the results by PPAR-γ inhibitor GW9662, PPAR-γ siRNA as well as overexpression of PPAR-γ and Nrf2 in vitro. Furthermore, our in vivo study showed that oridonin inhibited tumor growth with high safety via inducing apoptosis through activating PPAR-γ and inhibiting Nrf2 activation in xenograft model inoculated HOS tumor. Taken together, oridonin exerted a dramatic pro-apoptotic effect by activating PPAR-γ and inhibiting Nrf2 pathway in vitro and in vivo. Therefore, oridonin may be a promising and effective agent for human osteosarcoma in the future clinical applications.

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“…Recently, it was reported that several natural compounds resulted in a reduction in cell growth and an induction of cell death (such as autophagy and apoptosis) in cancer cells, accompanied by the accumulation of γ H2AX nuclear foci . Considering the previous studies reporting that oridonin caused a DNA damage response in human diffuse large B‐cell lymphoma and human breast cancer cells via induction of γ H2AX expression , it would be worthwhile to investigate whether oridonin facilitates the expression of γ H2AX in response to DNA damage in oral cancer. In the present study, we attempted to explore the possibility that oridonin acts as an apoptotic inducer upon DNA damage in the HSC‐3 and HSC‐4 human oral cancer cell lines.…”

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confidence: 99%

Oridonin induces apoptosis in human oral cancer cells via phosphorylation of histone H2AX

Yang

Shin

Lee

et al. 2017

European J Oral Sciences

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Oridonin, a natural diterpenoid purified from Rabdosia rubescens, has displayed beneficial biological activities, including anti-proliferation and anti-angiogenesis effects, in various types of cancers. However, the anti-cancer potential of oridonin and its mechanism in oral cancer have never previously been studied. In this study, we assessed the role of oridonin as an inducer of apoptosis in HSC-3 and HSC-4 human oral cancer cells. Our results showed that oridonin reduces the viability of human oral cancer cells and significantly increases the expression of γH2AX, a well-known marker of DNA damage. 4',6-Diamidino-2-phenylindole (DAPI) staining and western blotting showed that oridonin causes nuclear condensation and fragmentation, and induces cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, oridonin-induced γH2AX accumulation was partially abrogated by Z-VAD, a pan-caspase inhibitor. Taken together, our results suggest that oridonin can effectively induce apoptosis by augmenting the expression of γH2AX in response to DNA damage and might be a promising anti-cancer drug candidate for the treatment of oral cancer.

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Reactive oxygen species mediate oridonin-induced apoptosis through DNA damage response and activation of JNK pathway in diffuse large B cell lymphoma

Cited by 24 publications

References 33 publications

Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma

Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma

Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-γ and inhibiting Nrf2 pathway

Oridonin induces apoptosis in human oral cancer cells via phosphorylation of histone H2AX

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