Anticancer activity and underlying mechanism of neogambogic acid

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Abstract

Garcinia, a kind of dry resin secreted by Garcinia hanburyi Hook. F. G., is a traditional Chinese medicine with various biological functions such as detoxification, anti-inflammatory, and anthelmintic activities. Recent studies suggest that garcinia has potential anticancer activity. Increasing evidences indicate that the main active monomer gambogic acid isolated from garcinia can inhibit the growth of various cancer cells. Neogambogic acid is an isolated compound with a similar chemical structure as gambogic acid. Preliminary studies show that the neogambogic acid can selectively inhibit the growth of various cancer cells, and has a broader antitumor activity and lower toxicity than gambogic acid. In this review, we summarize the advances made in the investigation of the anti-tumor effect of neogambogic acid in recent years.

Most cited references 4

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Proteomic identification of molecular targets of gambogic acid: role of stathmin in hepatocellular carcinoma.

Pao-Hung Lin, X. Wang, Liang He … (2008)

Gamboge has been developed as an injectable drug for cancer treatment in China. In this study, the inhibition ratio and their IC(50) values of two derivatives from Gamboge in hepatocellular carcinoma (HCC) were determined. Proteomic approach was employed to reveal the target proteins of these two derivatives, gambogic acid (GA), and gambogenic acid (GEA). HCC cells were cultured under varied conditions with the addition of either GA or GEA. Twenty differentially expressed proteins were identified and the four most distinctly expressed proteins were further validated by Western blotting. GA and GEA revealed inhibitory effects on HCC cell proliferation. The expression of cyclin-dependent kinase 4 inhibitor A and guanine nucleotide-binding protein beta subunit 1 were upregulated by both xanthones, whilst the expression of 14-3-3 protein sigma and stathmin 1 (STMN1) were downregulated. Furthermore, overexpression of STMN1 in HCC cells decreased their sensitivity, whilst small interfering RNAs targeting STMN1 enhanced their sensitivity to GA and GEA. In conclusion, our study suggested for the first time that STMN1 might be a major target for GA and GEA in combating HCC. Further investigation may lead to a new generation of anticancer drugs exerting synergistic effect with conventional therapy, thus to promote treatment efficacy.

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Gambogenic acid induced mitochondrial-dependent apoptosis and referred to phospho-Erk1/2 and phospho-p38 MAPK in human hepatoma HepG2 cells.

Fenggen Yan, Mei Wang, Jiaming Li … (2012)

Gambogenic acid, identified from Gamboge, is responsible for anti-tumor effects, and has been shown to be a potential molecule against human cancers. In this study, the molecular mechanism of gambogenic acid-induced apoptosis in HepG2 cells was investigated. Gambogenic acid significantly inhibited cell proliferation and induced apoptosis. Acridine orange/ethidium bromide (AO/EB) staining was used to observe apoptosis, and then confirmed by transmission electron microscopy. Gambogenic acid induced apoptosis and morphological changes in mitochondria, and intracellular reactive oxygen species (ROS) and mitochondrial membrane permeabilization (MMP) in mitochondrial apoptosis pathway were also examined. Results showed that the levels of phospho-p38 and its downstream phospho-Erk1/2 of HepG2 cells increased in time- and concentration-dependent manners after gambogenic acid treatments. Additionally, gambogenic acid increased expression ratio of Bcl-2/Bax in mRNA levels, Western blotting analysis also further confirmed the reduced level of Bcl-2 and increase the expression level of Bax in HepG2 cells. These results indicated that gambogenic acid induced mitochondrial oxidative stress and activated caspases through a caspase-3 and caspase-9-dependent apoptosis pathway. Moreover, gambogenic acid mediated apoptosis and was involved in the phospho-Erk1/2 and phospho-p38 MAPK proteins expression changes in HepG2 cells. Copyright © 2011 Elsevier B.V. All rights reserved.

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Apoptosis induced by 1,3,6,7-tetrahydroxyxanthone in Hepatocellular carcinoma and proteomic analysis.

Wei-Ming Fu, Jin-Fang Zhang, Hua Wang … (2012)

Gamboge is a traditional Chinese medicine and our previous study showed that gambogic acid and gambogenic acid suppress the proliferation of HCC cells. In the present study, another active component, 1,3,6,7-tetrahydroxyxanthone (TTA), was identified to effectively suppress HCC cell growth. In addition, our Hoechst-PI staining and flow cytometry analyses indicated that TTA induced apoptosis in HCC cells. In order to identify the targets of TTA in HCC cells, a two-dimensional gel electrophoresis was performed, and proteins in different expressions were identified by MALDA-TOF MS and MS/MS analyses. In summary, eighteen proteins with different expressions were identified in which twelve were up-regulated and six were down-regulated. Among them, the four most distinctively expressed proteins were further studied and validated by western blotting. The β-tubulin and translationally controlled tumor protein were decreased while the 14-3-3σ and P16 protein expressions were up-regulated. In addition, TTA suppressed tumorigenesis partially through P16-pRb signaling. 14-3-3σ silence reversed the suppressive effect of cell growth and apoptosis induced by introducing TTA. In conclusion, TTA effectively suppressed cell growth through, at least partially, up-regulation of P16 and 14-3-3σ.

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Author and article information

Journal

Journal ID (publisher-id): CJNM

Title: Chinese Journal of Natural Medicines

Publisher: Elsevier

ISSN (Electronic): 1875-5364

Publication date (Electronic): 20 September 2018

Volume: 16

Issue: 9

Pages: 641-643

Affiliations

[1] ¹Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China

Author notes

*Corresponding author: CHEN Bao-An, Tel/Fax: +86-25-83272006, E-mail: cba8888@ 123456hotmail.com

These authors have no conflict of interest to declare.

Article

Publisher ID: S1875-5364(18)30103-1

DOI: 10.1016/S1875-5364(18)30103-1

SO-VID: 8cff3a03-c823-463d-8e24-1b85b44281ae

History

Date received : 02 November 2017

Funding

Funded by: Fundamental Research Funds for the Central Universities

Award ID: KYLX15-0186

Funded by: Key Medical Projects of Jiangsu Province

Award ID: BL2014078

Funded by: Key Discipline of Jiangsu Province

Award ID: 2016-2020

This work is supported by the Fundamental Research Funds for the Central Universities (No. KYLX15-0186), the Key Medical Projects of Jiangsu Province (No. BL2014078), and the Key Discipline of Jiangsu Province (No. 2016-2020).

Anticancer activity and underlying mechanism of neogambogic acid

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Abstract

Most cited references 4

Proteomic identification of molecular targets of gambogic acid: role of stathmin in hepatocellular carcinoma.

Gambogenic acid induced mitochondrial-dependent apoptosis and referred to phospho-Erk1/2 and phospho-p38 MAPK in human hepatoma HepG2 cells.

Apoptosis induced by 1,3,6,7-tetrahydroxyxanthone in Hepatocellular carcinoma and proteomic analysis.

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