Gambogic Acid is a Novel Anti-cancer Agent that Inhibits Cell Proliferation, Angiogenesis and Metastasis

Wang, Xu; Chen, Wantao

doi:10.2174/187152012802650066

Cited by 81 publications

(49 citation statements)

References 34 publications

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“…Gambogic acid, a caged xanthone from G. hanburyi Hook. f., has been tested in vitro and in vivo as a novel anticancer agent that inhibits cell proliferation, angiogenesis, and metastasis [21][22][23]. Interestingly, many caged Garcinia xanthones have been identified in the past several decades, and most of them display high cytotoxic efficacy against various cancer cells [24].…”

Section: Abbreviationsmentioning

confidence: 99%

Identification and Characterization of Anticancer Compounds Targeting Apoptosis and Autophagy from Chinese Native Garcinia Species

Lao

et al. 2014

Planta Med

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Natural compounds from medicinal plants are important resources for drug development. Active compounds targeting apoptosis and autophagy are candidates for anti-cancer drugs. In this study, we collected Garcinia species from China and extracted them into water or ethanol fractions. Then, we performed a functional screen in search of novel apoptosis and autophagy regulators. We first characterized the anti-proliferation activity of the crude extracts on multiple cell lines. HeLa cells expressing GFP-LC3 were used to examine the effects of the crude extracts on autophagy. Their activities were confirmed by Western blots of A549 and HeLa cells. By using bioassay guided fractionation, we found that two caged prenylxanthones from Garcinia bracteata, neobractatin and isobractatin, can significantly induce apoptosis and inhibit autophagy. Our results suggest that different Garcinia species displayed various degrees of toxicity on different cancer cell lines. Furthermore, the use of a high content screening assay to screen natural products was an essential method to identify novel autophagy regulators.

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Section: Abbreviationsmentioning

confidence: 99%

Identification and Characterization of Anticancer Compounds Targeting Apoptosis and Autophagy from Chinese Native Garcinia Species

Lao

et al. 2014

Planta Med

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“…An increasing number of studies tried to elucidating the molecular mechanisms of GA anti-tumor effects, and several critical signaling steps in carcinogenesis have been reported to be influenced by GA treatment (Wang and Chen, 2012). For example, GA arrested cell cycle at G2/M phase via disturbing CDK7 mediated phosphorylation of CDC2/P34 (Yu et al, 2007); GA could interact with transferrin receptor and induce rapid apoptosis of tumor cells (Pandey et al, 2007); GA inhibited cell proliferation not only by repressing hTERT transcriptional activity but also by posttranslational modification of hTERT (Zhao et al, 2008); GA can also inhibit tumor growth by repressing angiogenesis (Lu et al, 2007).…”

Section: Autophagy Inhibition Promotes Gambogic Acid-induced Suppressmentioning

confidence: 99%

Autophagy Inhibition Promotes Gambogic Acid-induced Suppression of Growth and Apoptosis in Glioblastoma Cells

Luo¹,

Cai²,

Lin³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Xanthones, polycyclic polyprenylated acylphloroglucinols (PPAPs), and benzophenones are the main chemicals from Garcinia plants 22 . Gambogic acid, a caged xanthone from Garcinia hanburyi , has been tested in vitro and in vivo as a novel anticancer agent that inhibits cell proliferation, angiogenesis, and metastasis 23 - 25 . The PPAPs have been used in antiseptics, antidepressants, and antibiotics for centuries and their mimics also show fascinating biological activities 26 , 27 .…”

Section: Introductionmentioning

confidence: 99%

The natural compound oblongifolin C inhibits autophagic flux and enhances antitumor efficacy of nutrient deprivation

et al. 2014

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Metabolic stress induces autophagy as an alternative source of energy and metabolites. Insufficient autophagy in nutrient-deprived cancer cells would be beneficial for cancer therapy. Here, we performed a functional screen in search of novel autophagy regulators from natural products. We showed that oblongifolin C (OC), a natural small molecule compound extracted from Garcinia yunnanensis Hu, is a potent autophagic flux inhibitor. Exposure to OC results in an increased number of autophagosomes and impaired degradation of SQSTM1/p62. Costaining of GFP-LC3B with LysoTracker Red or LAMP1 antibody demonstrates that autophagosome-lysosome fusion is blocked by OC treatment. Furthermore, OC inhibits lysosomal proteolytic activity by altering lysosomal acidification and downregulating the expression of lysosomal cathepsins. Importantly, OC can eliminate the tolerance of cancer cells to nutrient starvation. Starvation dramatically increases the susceptibility of cancer cells to OC-induced CASP3-dependent apoptosis in vitro. Subsequent studies in xenograft mouse model showed that OC has anticancer potency as revealed by increased staining of cleaved CASP3, LC3 puncta, and SQSTM1, as well as reduced expression of lysosomal cathepsins. Combined treatment with OC and caloric restriction potentiates anticancer efficacy of OC in vivo. Collectively, these data demonstrated that OC is a novel autophagic flux inhibitor and might be useful in anticancer therapy.

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Gambogic Acid is a Novel Anti-cancer Agent that Inhibits Cell Proliferation, Angiogenesis and Metastasis

Cited by 81 publications

References 34 publications

Identification and Characterization of Anticancer Compounds Targeting Apoptosis and Autophagy from Chinese Native Garcinia Species

Identification and Characterization of Anticancer Compounds Targeting Apoptosis and Autophagy from Chinese Native Garcinia Species

Autophagy Inhibition Promotes Gambogic Acid-induced Suppression of Growth and Apoptosis in Glioblastoma Cells

The natural compound oblongifolin C inhibits autophagic flux and enhances antitumor efficacy of nutrient deprivation

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