NF-κB and JNK mediated apoptosis and G 0 /G 1 arrest of HeLa cells induced by rubiarbonol G, an arborinane-type triterpenoid from Rubia yunnanensis.

Autor: Zeng GZ; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China; YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming 650500, PR China., Wang Z; School of Traditional Chinese Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, PR China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China., Zhao LM; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China., Fan JT; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China., Tan NH; School of Traditional Chinese Pharmacy and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, PR China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China. Electronic address: nhtan@cpu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2018 Jun 28; Vol. 220, pp. 220-227. Date of Electronic Publication: 2017 Oct 31.
DOI: 10.1016/j.jep.2017.10.026
Abstrakt: Ethnopharmacological Relevance: Rubia yunnanensis is a medicinal plant mainly grown in Yunnan province in Southwest China, and its root named "Xiaohongshen" has been used as a herb in Yunnan for the treatment of cancers. Three major types of chemical components, Rubiaceae-type cyclopeptides, quinones, and triterpenoids, were identified from R. yunnanensis, in which some of compounds including rubiarbonol G (RG), a unique arboriane-type triterpenoid, showed cytotoxicity on cancer cells. But the cytotoxic mechanism of RG has not been reported.
Aim of the Study: To investigate the cytotoxic mechanism of RG on cancer cells.
Materials and Methods: RG was evaluated its cytotoxicity on 7 cancer cell lines by the SRB assay, and detected the effect on apoptosis and cell cycle arrest by Annexin V-FITC/PI apoptosis assay and DNA contents analysis. The expression and activity of apoptosis and cell cycle related proteins were also investigated by western blot and caspase activity assay. Furthermore, the effect of RG on NF-κB signaling was also tested by luciferase assay, western blot, and immunofluorescence staining.
Results: RG showed potent cytotoxicity on 7 human cancer cell lines, whose activity was attributed to apoptosis induction and G 0 /G 1 arrest in HeLa cells. Results from the mechanism study showed that RG promoted the activation of ERK1/2 and JNK pathway in MAPK family, which in turn increased the expression of p53, thereby triggering the G 0 /G 1 arrest through p53/p21/cyclin D1 signaling. Moreover, RG-mediated JNK activation down-regulated the expression of the anti-apoptotic protein Bcl-2, which caused the release of cytochrome c to the cytosol and activated the cleavage of caspase cascade and poly(ADP-ribose) polymerase, thereby inducing apoptosis in HeLa cells. In addition, RG was also found to inhibit the activation of NF-κB signaling by down-regulating the expression and attenuating the translocation to nucleus of NF-κB p65, by which the down-stream p53, cyclin D1, Bcl-2, and caspases were regulated, thereby triggering apoptosis and G 0 /G 1 arrest in HeLa cells.
Conclusion: These results indicated that RG induces mitochondria-mediated apoptosis and G 0 /G 1 cell cycle arrest by activation of JNK signaling as well as inactivation of NF-κB pathway in HeLa cells, which suggests that RG is one of the key active ingredients accounting for the anti-tumor effect of R. yunnanensis.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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