Oridonin triggers apoptosis in colorectal carcinoma cells and suppression of microRNA-32 expression augments oridonin-mediated apoptotic effects

Yang, Jie; Jiang, Hongyun; Wang, Chunyu; Yang, Bo; Zhao, Lijun; Hu, Dongling; Qiu, Guang; Dong, Xiaolin; Xiao, Bin

doi:10.1016/j.biopha.2015.04.016

Cited by 30 publications

(27 citation statements)

References 46 publications

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“…16, 28, 30, 31, 32 But a very interesting finding grabbed our attention that although clear anti-proliferative activity was observed both in vitro and vivo, no typical apoptosis phenomenon was observed in SW480 cells, whereas clear apoptosis was detected in RKO cells using flow cytometry with Annexin V-FITC/PI labeling (Figure 1c). Thus, we hypothesized that oridonin caused cell death via a distinct process that was different from normal apoptosis in SW480 cells.…”

Section: Discussionmentioning

confidence: 96%

Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells

Mai

Xie

et al. 2017

Cell Death Dis

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The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells. Then miRNA profiling of SW480 cells revealed those intracellular signaling related to energy supply was affected by oridonin, suggesting that glucose metabolism is a potential target for CRC therapy. Moreover, our results indicated that oridonin induced metabolic imbalances by significantly inhibiting glucose uptake and reducing lactate export through significantly downregulating the protein levels of GLUT1 and MCT1 in vitro and vivo. However, the ATP level in oridonin-treated CRC cells was not decreased when oridonin blocked the glucose supply, indicating that oridonin induced autophagy process, an important ATP source in cancer cells. The observation was then supported by the results of LC3-II detection and transmission electron microscopy analysis, which confirmed the presence of autophagy. Furthermore, p-AMPK was rapidly deactivated following oridonin treatment, resulting in downregulation of GLUT1 and induction of autophagy in the cancer cells. Thus our finding helped to clarify the anticancer mechanisms of oridonin and suggested it could be applied as a glucose metabolism-targeting agent for cancer treatment.

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Section: Discussionmentioning

confidence: 96%

Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells

Mai

Xie

et al. 2017

Cell Death Dis

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“…1), is a diterpenoid compound (10). Previous studies have shown that oridonin has antitumor activities in vivo and in vitro (11)(12)(13), and oridonin inhibited proliferation of cancer cells by inducing autophagic pathways (14)(15)(16)(17)(18), arresting the cell cycle on G 0 /G 1 phase (19) or G 2 /M phase (20)(21)(22)(23)(24), inducing apoptosis of human laryngeal cancer cells (25), esophageal cancer (26), colorectal carcinoma (27), pancreatic cancer (28), hepato cellular carcinoma (29,30). However, few reports exist on oridonin-induced apoptosis on gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells

Gao

Tan

Zhu

et al. 2016

International Journal of Oncology

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Abstract.Oridonin is one of the most important antitumor active ingredients of Rabdosia rubescens. Recently published studies from our laboratory have demonstrated that oridonin was able to arrest human gastric cancer SGC-7901 cells at G 2 /M phase. However, little is known about inducing apoptosis in gastric cancer. The aim of this study was to investigate the effect of oridonin on antineoplastic capability of SGC-7901 cells and the detailed molecular mechanism of oridoninmediated intrinsic pathway of apoptosis. Cell proliferation was assessed by MTT assay while apoptosis induced by oridonin was determined by Hoechst 33342 staining assay and Annexin V/PI double staining assay. Early apoptotic rate was stained by Annexin V/PI and detected by flow cytometry. Apoptosis pathway was analyzed by western blot analysis of Bcl-2, Bax, cytochrome c and caspase-3 expression. The results showed that oridonin was able to inhibit the SGC-7901 cell proliferation, the 50% growth inhibition (IC 50 ) was 22.74 µM. Oridonin could induce cell apoptosis of SGC-7901 cells and the early apoptotic rates induced by 0, 20, 40, 80 µmol/l oridonin were 1.53±0.67, 3.33±0.29, 84.80±0.82 and 96.43±0.51%, respectively. Western blot analysis revealed that oridonin downregulated Bcl-2 protein (the anti-apoptotic factor) and upregulated Bax protein (pro-apoptotic factor), eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. Furthermore, oridonin induced the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase-3. Taken together, the current study suggested that oridonin induced apoptosis in SGC-7901 cells via the mitochondrial signal pathway, which may represent one of the major mechanisms of oridonin-mediated apoptosis in SGC-7901 cells.

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“…On the other hand, the diterpenoid C from Radix curcumae in human colon adenocarcinoma SW620 cells significantly inhibited cell proliferation and induced apoptosis by MAPK signalling and caspase‐3 dependent pathways (Shen et al , ). The other antiproliferative and apoptosis‐inducing diterpenes are pseudolaric acid B (Yu et al , ), oridonin (Yang et al , ), pseudolaric acid B (Li and Hong, ), crypotanshinone (Yao et al , ), tanshinone IIA (Zhang et al , ) and tonantzitlolone A and its synthetic enantiomer (Pfeffer et al , ). Penitrem A in MDA‐MB‐231 mammary cancer cells exerted antiproliferative, antimigratory and total β‐catenin suppressing effects (Sallam et al , ).…”

Section: Diterpenic Anticancer Traitsmentioning

confidence: 99%

“…The other antiproliferative 700 M.T. ISLAM and apoptosis-inducing diterpenes are pseudolaric acid B (Yu et al, 2015), oridonin (Yang et al, 2015a), pseudolaric acid B (Li and Hong, 2015), crypotanshinone (Yao et al, 2015b), tanshinone IIA (Zhang et al, 2016b) and tonantzitlolone A and its synthetic enantiomer (Pfeffer et al, 2016). Penitrem A in MDA-MB-231 mammary cancer cells exerted antiproliferative, antimigratory and total β-catenin suppressing effects (Sallam et al, 2013).…”

Section: Effects On Cell Proliferation and Differentiationmentioning

confidence: 99%

Diterpenes and Their Derivatives as Potential Anticancer Agents

Islam

2017

Phytotherapy Research

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As therapeutic tools, diterpenes and their derivatives have gained much attention of the medicinal scientists nowadays. It is due to their pledging and important biological activities. This review congregates the anticancer diterpenes. For this, a search was made with selected keywords in PubMed, Science Direct, Web of Science, Scopus, The American Chemical Society and miscellaneous databases from January 2012 to January 2017 for the published articles. A total 28, 789 published articles were seen. Among them, 240 were included in this study. More than 250 important anticancer diterpenes and their derivatives were seen in the databases, acting in the different pathways. Some of them are already under clinical trials, while others are in the nonclinical and/or pre-clinical trials. In conclusion, diterpenes may be one of the lead molecules in the treatment of cancer. Copyright © 2017 John Wiley & Sons, Ltd.

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Oridonin triggers apoptosis in colorectal carcinoma cells and suppression of microRNA-32 expression augments oridonin-mediated apoptotic effects

Cited by 30 publications

References 46 publications

Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells

Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells

Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells

Diterpenes and Their Derivatives as Potential Anticancer Agents

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