Gambogic acid inhibits the growth of osteosarcoma cells in vitro by inducing apoptosis and cell cycle arrest

Zhao, Wei; Zhou, Shifeng; Zhang, Zhipeng; Xu, Gongping; Li, Xiaobo; Yan, Jinglong

doi:10.3892/or.2011.1189

Cited by 22 publications

(11 citation statements)

References 23 publications

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“…Resistance to L-OHP remains one of the major obstacles in chemotherapy for CRC, and it is essential to identify novel drugs to overcome or reverse L-OHP resistance. GA is a traditional Chinese medicine with multi-target anticancer effects, including the inhibition of proliferation ( 20 ), induction of apoptosis ( 21 ), cell cycle arrest ( 22 ), and inhibition of angiogenesis ( 23 ), invasion and metastasis ( 24 ). GA was also identified to exhibit inhibitory effects on resistance to anticancer drugs in CRC ( 12 ), breast ( 13 ), ovarian ( 14 ), gastric ( 15 ) and human epithelial cancer ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels

et al. 2018

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Resistance to oxaliplatin (L-OHP) is a major obstacle to successful chemotherapy in colorectal cancer (CRC). In the present study, the ability of gambogic acid (GA) to reverse L-OHP resistance in CRC LoVo cells was investigated. L-OHP-resistant LoVo/L-OHP cells were established by exposing them to increasing concentrations of L-OHP. GA-reversed L-OHP-sensitive LoVo/L-OHP/GA cells were established by exposure to 0.5 µmol/l GA for 2 weeks. A Cell Counting Kit-8 assay was used to assess levels of proliferation. Flow cytometry was applied to detect apoptosis rates. Transwell assays were used to analyse invasion. Inductively coupled plasma mass spectrometry was used to determine intracellular platinum (Pt) content. Western blot analysis was used to reveal the protein levels of Human copper transporter 1 (hCTR1), Copper-transporting p-type adenosine triphosphatases 1 (ATP7A) and Copper-transporting p-type adenosine triphosphatases 2 (ATP7B). LoVo/L-OHP and LoVo/L-OHP/GA cell lines were successfully established, and it was identified that L-OHP inhibited the proliferation of LoVo, LoVo/L-OHP and LoVo/L-OHP/GA cells in a dose-dependent manner. Compared with the parent LoVo cells, the anti-apoptosis and invasion properties of LoVo/L-OHP cells were enhanced, and were reversed by GA treatment. Intracellular Pt content was highest in the LoVo cells, followed by LoVo/L-OHP/GA cells, and then lowest in the LoVo/L-OHP cells. Downregulated hCTP1 and upregulated ATP7A and ATP7B were associated with L-OHP resistance, and GA reversed the resistance by increasing levels of hCTR1 and decreasing levels of ATP7A and ATP7B. In conclusion, GA has the potential ability to reverse L-OHP resistance in CRC cells by increasing intracellular Pt content, which it achieves by increasing hCTR1 levels and decreasing ATP7A and ATP7B levels. GA may represent a promising treatment agent for L-OHP resistance.

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Section: Discussionmentioning

confidence: 99%

Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels

et al. 2018

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“…In a number of previous reports, GA was found to induce apoptosis in tumor cells ( 19 , 20 ). However, in the present study, no effect of GA on caspase-3, 8 and 9 activities was identified in the NCI-H1993 xenograft model.…”

Section: Discussionmentioning

confidence: 88%

Antitumor activity of gambogic acid on NCI-H1993 xenografts via MET signaling pathway downregulation

Li¹,

Yang²,

Li³

et al. 2015

Oncology Letters

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The present study aimed to investigate the anti-tumor mechanisms of gambogic acid (GA) on NCI-H1993 xenografts in vivo. Non-small cell lung carcinoma NCI-H1993 cells, which harbor a MET gene amplification, were subcutaneously injected into athymic nude mice. The mice were randomly assigned to treatment with 10, 20 or 30 mg/kg GA for 3 weeks. At the end of the efficacy study, all the mice were sacrificed and the tumor tissues were subjected to western blot analysis and immunohistochemical (IHC) staining. GA inhibited NCI-H1993 xenograft tumor growth in a dose-dependent manner. Western blot analysis demonstrated that expression of phosphorylated (p)-MET and its downstream signaling molecules p-AKT and p-ERK1/2 were significantly inhibited by GA. IHC analysis of Ki-67 expression demonstrated that GA treatment resulted in dose-dependent inhibition of tumor cell proliferation. GA exerted antitumor effects on NCI-H1993 xenografts in vivo by direct regulation of the MET signaling pathway. Theses antitumor effects were primarily a result of its anti-proliferation function.

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“…CDK and cyclin family proteins regulated cell cycle progress via transporting nutrients and transducing growth factors into cells. CDK4/6 related to Cyclin D1 was essential for regulating G1, 24 and they were inhibited by p16. Cyclin E1 combined with CDK2 induced cell cycle in the late G1 stage, and CDK2/Cyclin E1 complex was inhibited by p21 (tumor suppressor gene).…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Analysis and Experimental Pharmacology Study Explore the Mechanism of Gambogic Acid against Endometrial Cancer

Xia

Tang

2021

ACS Omega

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Endometrial cancer (EC) is one of the three most common gynecological cancers in female groups. Gambogic acid (GA), a natural caged xanthone, exerts significantly antitumor effects on many cancers. However, its efficacy on EC and pharmacological mechanism of action remain marginal up to now. This study suggested that GA had significant inhibitory effects on EC in vitro and in vivo, and no toxicity to normal cells or mice. In detail, GA suppressed cell proliferation, induced cell apoptosis, and cell cycle arrest at G 0 /G 1 stage, complied with the network pharmacology analysis, showed that the PI3K/Akt pathways were the most important signaling, and their protein and mRNA expression levels were confirmed by qRT-PCR and Western blot experiments. In all, our study first proved that GA could inhibit cell proliferation, induce cell apoptosis, and cell cycle arrest at G 0 /G 1 stage via the PI3K/Akt pathways, so GA would be a good therapy for EC.

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Gambogic acid inhibits the growth of osteosarcoma cells in vitro by inducing apoptosis and cell cycle arrest

Cited by 22 publications

References 23 publications

Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels

Gambogic acid reverses oxaliplatin resistance in colorectal cancer by increasing intracellular platinum levels

Antitumor activity of gambogic acid on NCI-H1993 xenografts via MET signaling pathway downregulation

Network Pharmacology Analysis and Experimental Pharmacology Study Explore the Mechanism of Gambogic Acid against Endometrial Cancer

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