The cytostatic and cytotoxic effects of oridonin (Rubescenin), a diterpenoid from Rabdosia rubescens, on tumor cells of different lineage

Chen, Sophie; Gao, Jian; Halicka, H. Dorota; Huang, Xuan; Traganos, Frank; Darżynkiewicz, Zbigniew

doi:10.3892/ijo.26.3.579

Cited by 56 publications

(75 citation statements)

References 32 publications

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“…21,22 In the present study, we found that EriB, a diterpene compound isolated from Isodon eriocalyx var. laxiflora, possessed an antiproliferation effect on leukemia/ lymphoma cells, especially on t(8;21) leukemia cells.…”

Section: Discussionmentioning

confidence: 74%

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner

et al. 2006

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Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-X L downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-jB inactivation by preventing NF-jB nuclear translocation and inducing IjBa cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8;21) leukemia blasts and caused AML1-ETO degradation. In murine t(8;21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8;21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways.

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Section: Discussionmentioning

confidence: 74%

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner

et al. 2006

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“…Research showed that oridonin was one of the most important antitumor active ingredient of Rabdosia rubescens (33)(34)(35)(36). Our previous studies showed that oridonin could arrest the cell cycle in G 2 /M phase in human gastric cancer SGC-7901 cells (3).…”

Section: Discussionmentioning

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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“…Oridonin, the most biologically active molecule purified from RRE, has been studied extensively for its effects on breast cancer (12,13), leukemia (14), cervical cancer (15), melanoma (16)(17)(18) and prostate cancer (19). Oridonin has previously been shown to inhibit the proliferation of a wide variety of human cancer cells, including prostate (lncap, du-145 and pc3), breast (mcF-7 and mda-mB-231) and non-small cell lung (nci-h520, nci-h460 and nci-h1299) cancers, acute promyelocytic leukemia (nB4) and glioblastoma multiforme (u118 and u138) (11).…”

Section: Discussionmentioning

confidence: 99%

Genomic and in vivo evidence of synergy of a herbal extract compared to its most active ingredient: Rabdosia rubescens vs. oridonin

Wong

Zhang

Kesler

et al. 2010

Experimental and Therapeutic Medicine

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Abstract. Rabdosia rubescens is a herbal root extract of traditional Chinese medicine (TCM) used to treat inflammatory diseases and oral cancers. a key principle of tcm is that multiple ingredients in a plant extract are more effective and less toxic than a single purified active ingredient or a purified drug derived from a plant product. Rabdosia rubescens extract (RRE) contains terpenoids and flavonoids, but the most active ingredient within the extract attributed to the inhibition of cancer is the kaurene diterpene, oridonin. in order to research synergy with a complete plant extract, the effects of rrE on the inhibition of prostate cancer cell proliferation were compared to the effects of pure oridonin alone in vitro. three groups of 8 Scid mice bearing human prostate cancer xenografts (lapc-4) were administered either rrE containing 0.02 mg/g oridonin, pure oridonin at a dose of 0.02 mg/g, or pure oridonin at a dose of 0.1 mg/g, by gavage for 5 days/week for 4 weeks. rrE and pure oridonin at 0.1 mg/g inhibited tumor growth to a similar extent, while oridonin at a dose of 0.02 mg/g did not. Therefore, in comparison to RRE, five times more pure oridonin was required to obtain equivalent prostate xenograft growth inhibition. Since the nuclear factor-κB signaling pathway and inflammation are implicated in prostate carcinogenesis, gene microarray analysis was conducted and demonstrated activation of genes by rrE that was not evident with oridonin treatment alone. this study demonstrated that genomic methods and xenograft studies are capable of demonstrating the benefits of the synergy of whole plant extracts rather than active ingredients isolated and purified as drugs. IntroductionBotanical extracts are used for the prevention and treatment of common conditions by 80% of the world's population according to estimates made by the World health Organization (1). drugs are produced from botanical sources by isolation and purification of the most active ingredients, while other substances in the raw fraction are separated. Synergistic interactions of mixtures of bioactive constituents and related substances or analogs in plant extracts have been proposed to occur with the most active ingredient. these interactions help explain the improved effectiveness of extracts containing multiple ingredients compared to drugs developed from single constituents.We previously studied the action and metabolism of chinese red yeast rice (Monascus purpureus Went) (crYr), a dietary supplement containing monacolins, one of which (monacolin K) is identical in structure to the statin drug lovastatin, and to unsaturated fatty acids and phytosterols capable of lowering low-density lipoprotein (ldl) cholesterol in humans (2-5). the apparent bioactivity of crYr containing 6 mg of Monacolin K was equivalent to 20 mg of purified lovastatin. moreover, crYr is well tolerated in patients who are intolerant to statin drugs (6), suggesting that the lower amounts of active substances, enhanced action and more complete metabolism in comparison to a d...

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The cytostatic and cytotoxic effects of oridonin (Rubescenin), a diterpenoid from Rabdosia rubescens, on tumor cells of different lineage

Cited by 56 publications

References 32 publications

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner

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

Genomic and in vivo evidence of synergy of a herbal extract compared to its most active ingredient: Rabdosia rubescens vs. oridonin

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