Gambogenic Acid Inhibits Proliferation of A549 Cells through Apoptosis-Inducing and Cell Cycle Arresting

Li, Qinglin; Cheng, Hui; Zhu, Guoqi; Li, Yang; Zhou, An; Wang, Xiaoshan; Fang, Nianbai; Lun-zhu, Xia; Su, Jingjing; Wang, Mei; Peng, D Z; Xu, Qi

doi:10.1248/bpb.33.415

Cited by 80 publications

(72 citation statements)

References 18 publications

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“…GNA has been confirmed as the anti-tumor component of the traditional Chinese drug cambogia (Lei et al, 2003). Accumulating evidence indicates that GNA has a potential anti-tumor effect in many tumor cells (Li et al, 2010;Chen et al, 2012;Yan et al, 2012), but only Li et al demonstrated that GNA inhibited tumor growth in A549 xenograft nude mouse models (Li et al, 2010). In order to determine whether GNA plays an anti-tumor role in other tumors in vivo, MDA-MB-231 cell, an aggressive breast cancer cell line, was been chosen.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, we did not continue to investigate the detail signaling pathways. Li et al have reported that GNA can inhibit A549 cell proliferation through apoptosis by inducing the up-regulation of the p38 MAPK cascade and cell cycle arrest (Li et al, 2010;Yan et al, 2012). Chen et al found that GNA induced time-and dose-dependent growth inhibition and apoptosis Akt pathway inactivation in U251 glioblastoma cells (Chen et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Only one study demonstrated that GNA could effectively inhibit tumor growth in A549 xenograft nude mice models (Li et al, 2010). However, the detail mechanism of GNA suppressed tumor growth was not studied in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Gambogenic Acid Induction of Apoptosis in a Breast Cancer Cell Line

Zhou¹,

Luo²,

Wang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Gambogenic acid is a major active compound of gamboge which exudes from the Garcinia hanburyi tree. Gambogenic acid anti-cancer activity in vitro has been reported in several studies, including an A549 nude mouse model. However, the mechanisms of action remain unclear. Methods: We used nude mouse models to detect the effect of gambogenic acid on breast tumors, analyzing expression of apoptosis-related proteins in vivo by Western blotting. Effects on cell proliferation, apoptosis and apoptosis-related proteins in MDA-MB-231 cells were detected by MTT, flow cytometry and Western blotting. Inhibitors of caspase-3,-8,-9 were also used to detect effects on caspase family members. Results: We found that gambogenic acid suppressed breast tumor growth in vivo, in association with increased expression of Fas and cleaved caspase-3,-8,-9 and bax, as well as decrease in the anti-apoptotic protein bcl-2. Gambogenic acid inhibited cell proliferation and induced cell apoptosis in a concentration-dependent manner. Conclusion: Our observations suggested that Gambogenic acid suppressed breast cancer MDA-MB-231 cell growth by mediating apoptosis through death receptor and mitochondrial pathways in vivo and in vitro.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Gambogenic Acid Induction of Apoptosis in a Breast Cancer Cell Line

Zhou¹,

Luo²,

Wang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Gamboge, a well-known herbal medicine derived from the Garcinia hanburyi tree, shows widely pharmacological activities including detoxification, anti-inflammatory and parasiticide effects (Asano et al, 1996;Li et al, 2010). Its main active components includes gambogenic acid (GNA, Figure 1a) and gamboge acid (GA, Figure 1b), and GNA exhibits stronger and broader pharmacological activities (Zhou et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Nanosuspensions as delivery system for gambogenic acid: characterization and in vitro/in vivo evaluation

Yuan

Zhang

et al. 2015

Drug Delivery

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Nanosuspensions (NS) can enhance the saturation solubility and dissolution velocity of poorly soluble drugs. PEG as a non-ionic surfactant plays an important role in surface modification of nanoparticles for prolonging in vivo circulation. In this study, anti-solvent precipitation method was introduced to prepare gambogenic acid nanosuspensions (GNA-NS) with PVPK30 and PEG2000 as stabilizers to settle the disadvantages of GNA. The obtained nanoparticles were spherical with a mean particle size of 183.7 nm and a zeta potential of À22.8 mV.The entrapment efficiency and drug loading of the resultant formulation were 97.3 and 29.73%. X-ray diffraction analysis confirmed the amorphous phase of GNA in NS. Fourier transform infrared indicated there may be hydrogen bond interaction between the drug and excipients. After lyophilization of GNA-NS, the freeze-dried powder displayed sufficient longterm physical stability at 4 and 25 C. In comparison to GNA solution, in vitro studies of GNA-NS showed much slower release and higher cytotoxicity in HepG2 cells. What's more, the pharmacokinetic study in rats revealed that the AUC 0-1 and t 1/2 of GNA-NS were increased 2.63-and 1.77-fold than that of the reference formulation. Taken together, in vitro/in vivo evaluations showed NS would be an effectively strategy to change the poor aqueous solubility and prolong the half-life for GNA. The GNA-NS with enhanced bioavailability and drug efficacy provided a promising delivery system for the application of GNA. KeywordsCytotoxicity, gambogenic acid, in vivo pharmacokinetics, in vitro release, nanosuspensions History

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“…Available evidence suggests that GNA being the best representative, has the most potential of broad spectrum anticancer drug candidate, which has shown to have a strong anti-tumor activity against gastric carcinoma, hepatoma, breast cancer and lymphatic sarcoma in vitro and in vivo (Li et al, 2010), which mostly attributes that GNA is capable in arresting the cancerous cells to G 0 /G 1 with regulating expression of cyclin D1 and cyclo-oxygenase(COX)-2 (Yan et al, 2011). However, its therapeutic potential has been restricted mainly due to its irritation to the blood vessel, very low aqueous solubility and poor bioavailability or toxicity profiles.…”

Section: Introductionmentioning

confidence: 99%

PEGylated non-ionic surfactant vesicles as drug delivery systems for Gambogenic acid

et al. 2013

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Gambogenic acid (GNA), a popular Chinese traditional medicine, has its limitations of coming into use due to its low aqueous solubility and poor bioavailability. In this study, therefore, the PEGylated non-ionic surfactant vesicles drug delivery systems were prepared from biocompatible non-ionic surfactant of Span60, cholesterol and dicetyl phosphate (DCP) by the improved ethanol injection method, and were modified with a polyethylene glycol monostearate15 (PEG15-SA). PEG15-SA, as a biocompatible, non-toxic and non-immunogenic hydrophilic segment, was grafted onto the surface of colloidal niosomes carries to reduce the uptake by the reticuloendothelial system (RES), prolonging the circulation time and attaining higher entrapment efficiency. To our knowledge, this work is the first to report that PEG15-SA was applied to coating of niosomes for encapsulation of GNA. The optimized PEG-GNA-NISVs (P-GNA-NISVs) were characterized in terms of mean vesicles size, polydispersity index (PDI), Zeta potential and entrapment efficiency of the P-GNA-NISVs. The results showed that the mean diameter, PDI, Zeta potential, and the entrapment efficiency of the P-GNA-NISVs were 70.1 nm, 0.166, À44.3 mV and 87.74%, respectively. Furthermore, the release studies of GNA from PEGylated niosomes in vitro and the pharmacokinetics in vivo exhibited a prolonged release profile as studied over 24 h. In conclusion, the result suggests that P-GNA-NISVs prepared in this way not only have higher encapsulation capacity, more colloidal stability but also offer an approach that the PEGylated niosomes is a promising carrier for anticancer GNA.

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Gambogenic Acid Inhibits Proliferation of A549 Cells through Apoptosis-Inducing and Cell Cycle Arresting

Cited by 80 publications

References 18 publications

Gambogenic Acid Induction of Apoptosis in a Breast Cancer Cell Line

Gambogenic Acid Induction of Apoptosis in a Breast Cancer Cell Line

Nanosuspensions as delivery system for gambogenic acid: characterization and in vitro/in vivo evaluation

PEGylated non-ionic surfactant vesicles as drug delivery systems for Gambogenic acid

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