Discovery and development of natural product oridonin-inspired anticancer agents

Ding, Ye; Ding, Chunyong; Ye, Na; Liu, Zhiqing; Wold, Eric A.; Chen, Haiying; Wild, Christopher; Shen, Qiang; Zhou, Jia

doi:10.1016/j.ejmech.2016.06.015

Cited by 144 publications

(107 citation statements)

References 127 publications

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“…It has a wide range of biological effects, such as anticancer, antibacterial, and anti‐inflammatory activities . And, many oridonin derivatives have been designed and synthesized . Oridonin has strong anticancer activity that can extend the survival period of models of transplanted human esophageal and gastric tumor in mice .…”

Section: Introductionmentioning

confidence: 99%

“…14 And, many oridonin derivatives have been designed and synthesized. 14,15 Oridonin has strong anticancer activity that can extend the survival period of models of transplanted human esophageal and gastric tumor in mice. 16 As reported in the literature, oridonin can induce apoptosis or cell cycle arrest in pancreatic cancer, gastric cancer, liver cancer, prostate cancer, and colorectal cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma

et al. 2019

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Oridonin could induce NB (neuroblastoma) cells growth inhibition by inducing apoptosis and cell cycle arrest, and the molecular mechanisms behind the effects deserve to be further explored. Here, oridonin was confirmed to cause the reactivation of p53 (cellular tumor antigen p53) to promote the expression of a series of apoptosis‐ and cell cycle arrest‐related proteins for the biological effects. During the process, oridonin relied on the caspase activation to cleave p53‐induced Mdm2 (E3 ubiquitin‐protein ligase Mdm2) to generate Mdm2‐p60. The generation of Mdm2‐p60 stabilized p53, and resulted in p53 accumulation for p53 continuous activation. In our research, it was also found that the reactivation of p53 induced by oridonin was closely related with the generation of ROS (reactive oxygen species). Taken together, these findings explain that oridonin exerts its anticancer activity partially by targeting the Mdm2‐p53 axis in NB cells, which lay an experimental base for future research of exploring the effects and molecular mechanisms of oridonin.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma

et al. 2019

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“…Oridonin is the main active ingredient in an herb named Rabdosia rubescens . This herb has been found to exhibit various medical effects, such as anti‐cancer, antibacterial, and anti‐inflammatory effects (Bohanon et al, ; Ding et al, ; He et al, ; J. Xu, Wold, Ding, Shen, & Zhou, ). As a natural compound extracted from Rabdosia rubescens , oridonin has been increasingly gaining attention (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Oridonin ameliorates carbon tetrachloride‐induced liver fibrosis in mice through inhibition of the NLRP3 inflammasome

Liu

Qin

Bi-xian

et al. 2020

Drug Development Research

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Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) and accumulation of the extracellular matrix. There are limitations in the current therapies for liver fibrosis. Recently, oridonin was shown to induce apoptosis in HSCs. Thus, we aimed to determine the roles of oridonin in chronic liver injury and fibrosis. Liver fibrosis was induced by CCl 4 in mice injected intraperitoneally with oridonin for 6 weeks. The administration of oridonin significantly attenuated liver injury and reduced ALT levels. In addition, Sirius Red staining and the expression of α-smooth muscle actin (α-SMA) were significantly reduced by oridonin in murine livers with fibrosis. The expression of NLRP3, caspase-1, and IL-1β was downregulated with the oridonin treatment. Furthermore, the expression of F4/80 in liver tissues was also decreased by oridonin treatment. These results demonstrate that oridonin ameliorates chronic liver injury and fibrosis. Mechanically, oridonin may inhibit the activity of the NLRP3 inflammasome and inflammation in the liver. These results highlight the potential of oridonin as a therapeutic agent for liver fibrosis. K E Y W O R D Scollagen deposition, HSCs activation, liver fibrosis, NLRP3, oridonin

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“…Natural products have historically been invaluable as a source of therapeutic agents, and served human kind in the treatment of various diseases for centuries [6, 7]. It is roughly estimated that half of modern marketed drugs originate from natural products [8].…”

Section: Introductionmentioning

confidence: 99%

Plumbagin Triggers ER Stress-Mediated Apoptosis in Prostate Cancer Cells via Induction of ROS

Huang

Xie

Pan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide. Currently available therapies for hormone-refractory PCa are only marginally effective. Plumbagin (PLB), a natural naphthoquinone isolated from the traditional folk medicine Plumbago zeylanica, is known to selectively kill tumor cells. Nevertheless, antitumor mechanisms initiated by PLB in cancer cells have not been fully defined. Methods: MTT assay was used to evaluate the effect of PLB on the viability of cancer cells. Cell apoptosis and reactive oxygen species (ROS) production were determined by flow cytometry. Protein expression was detected by western blotting. In vivo anti-tumor effect was measured by using tumor xenoqraft model in nude mice. Results: In the present study, we found that PLB decreases cancer cell growth and induces apoptosis in DU145 and PC-3 cells. In addition, by increasing intracellular ROS levels, PLB induced a lethal endoplasmic reticulum stress response in PCa cells. Importantly, blockage of ROS production significantly reversed PLB-induced ER stress activation and cell apoptosis. In vivo, we found that PLB inhibits the growth of PCa xenografts without exhibiting toxicity Treatment of mice bearing human PCa xenografts with PLB was also associated with induction of ER stress activation. Conclusion: Inducing ER stress by PLB thus discloses a previously unrecognized mechanism underlying the biological activity of PLB and provides an in-depth insight into the action of PLB in the treatment of hormone-refractory PCa.

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Discovery and development of natural product oridonin-inspired anticancer agents

Cited by 144 publications

References 127 publications

Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma

Oridonin induces Mdm2‐p60 to promote p53‐mediated apoptosis and cell cycle arrest in neuroblastoma

Oridonin ameliorates carbon tetrachloride‐induced liver fibrosis in mice through inhibition of the NLRP3 inflammasome

Plumbagin Triggers ER Stress-Mediated Apoptosis in Prostate Cancer Cells via Induction of ROS

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