Gambogic acid-loaded magnetic Fe3O4 nanoparticles inhibit Panc-1 pancreatic cancer cell proliferation and migration by inactivating transcription factor ETS1

Chen, Baoan; Wang, Cailian; Zhang, Haijun

doi:10.2147/ijn.s28509

Cited by 21 publications

(11 citation statements)

References 32 publications

(35 reference statements)

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“…Pancreatic cancer is well recognized as an extremely challenging disease on multiple fronts, which is characterized by late detection, poor prognosis, and aggressive metastasis. 29 , 30 Early detection is uncommon with no >15%–20% of the patients being amenable for curative intent surgery at the time of diagnosis. 12 Even in these cases, 5-year overall survival is still only 22%.…”

Section: Clinical Trials Of Onivyde For the Therapy Of Multiple Solidmentioning

confidence: 99%

Onivyde for the therapy of multiple solid tumors

Zhang¹

2016

OTT

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142

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Drug delivery system based on nanobiotechnology can improve the pharmacokinetics and therapeutic index of chemotherapeutic agents, which has revolutionized tumor therapy. Onivyde, also known as MM-398 or PEP02, is a nanoliposomal formulation of irinotecan which has demonstrated encouraging anticancer activity across a broad range of malignancies, including pancreatic cancer, esophago-gastric cancer, and colorectal cancer. This up-to-date review not only focuses on the structure, pharmacokinetics, and pharmacogenetics of Onivyde but also summarizes clinical trials and recommends Onivyde for patients with advanced solid tumors.

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Section: Clinical Trials Of Onivyde For the Therapy Of Multiple Solidmentioning

confidence: 99%

Onivyde for the therapy of multiple solid tumors

Zhang¹

2016

OTT

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142

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“…Gambogic acid induces apoptosis of tumor cells and destroys cancer cells by increasing the levels of active oxygen, inhibiting the NF-κB, MAPK/ERK, and PI3K/AKT signaling pathways [ 21 ]. However, there are few studies on the effects of GA in pancreatic cancer, and the specific mechanisms underlying those effects remain unclear [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Gambogic acid sensitizes gemcitabine efficacy in pancreatic cancer by reducing the expression of ribonucleotide reductase subunit-M2 (RRM2)

Xia

Wang

Song

et al. 2017

J Exp Clin Cancer Res

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BackgroundPancreatic cancer is susceptible to gemcitabine resistance, and patients receive less benefit from gemcitabine chemotherapy. Previous studies report that gambogic acid possesses antineoplastic properties; however, to our knowledge, there have been no specific studies on its effects in pancreatic cancer. Therefore, the purpose of this study was to explore whether increases the sensitivity of pancreatic cancer to gemcitabine, and determine the synergistic effects of gambogic acid and gemcitabine against pancreatic cancer.MethodsThe effects of gambogic acid on cell viability, the cell cycle, and apoptosis were assessed using 4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and flow cytometry in pancreatic cancer cell lines. Protein expression was detected by western blot analysis and mRNA expression was detected using q-PCR. A xenograft tumor model of pancreatic cancer was used to investigate the synergistic effects of gambogic acid and gemcitabine.ResultsGambogic acid effectively inhibited the growth of pancreatic cancer cell lines by inducing S-phase cell cycle arrest and apoptosis. Synergistic activity of gambogic acid combined with gemcitabine was observed in PANC-1 and BxPC-3 cells based on the results of MTT, colony formation, and apoptosis assays. Western blot results demonstrated that gambogic acid sensitized gemcitabine-induced apoptosis by enhancing the expression of cleaved caspase-3, cleaved caspase-9, cleaved-PARP, and Bax, and reducing the expression of Bcl-2. In particular, gambogic acid reduced the expression of the ribonucleotide reductase subunit-M2 (RRM2) protein and mRNA, a trend that correlated with resistance to gemcitabine through inhibition of the extracellular signal-regulated kinase (ERK)/E2F1 signaling pathway. Treatment with gambogic acid and gemcitabine significantly repressed tumor growth in the xenograft pancreatic cancer model. Immunohistochemistry results demonstrated a downregulation of p-ERK, E2F1, and RRM2 in mice receiving gambogic acid treatment and combination treatment.ConclusionsThese results demonstrate that gambogic acid sensitizes pancreatic cancer cells to gemcitabine in vitro and in vivo by inhibiting the activation of the ERK/E2F1/RRM2 signaling pathway. The results also indicate that gambogic acid treatment combined with gemcitabine might be a promising chemotherapy strategy for pancreatic cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0579-0) contains supplementary material, which is available to authorized users.

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“…Furthermore, both compounds in the xenograft cancer model significantly repressed tumor growth and down regulated the p-ERK, E2F1, and RRM2 (Xia et al, 2017;Saeed et al, 2014). In Panc-1 pancreatic cancer cells, gambogic acidloaded magnetic Fe3O4 nanoparticles significantly inhibited the ETS1-mediated proliferation and migration of cells, lowered the expression of ETS1, as well as it down-streamed target genes cyclin D1, u-PA and VEGF (Wang et al, 2012). In another study, encapsulation of GA with magnetic Fe3O4 nanoparticles improved anticancer potential via induction of apoptosis, increasing of Bax, caspase 3 and caspase 9, decreasing protein expressions of Bcl-2 (Wang et al, 2011).…”

Section: Pancreatic Cancermentioning

confidence: 92%

Gambogic Acid as Anticancer Agent: A Review

Gilani¹,

Imran²,

Haq³

et al. 2020

Preprint

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Gambogic acid, a common traditional Chinese medicine and widely distributed throughout South China, Vietnam, Cambodia, and Thailand. It is prenylated xanthone which is the significant bioactive compound of gamboge. Gambogic acid is known as a strong apoptotic inducer in cancer cells. It has been found as strong anticancer agent against various types of cancer cells lines such as breast cancer, pancreatic, and cervical cancer. It induces apoptosis, down regulates the anti-apoptotic proteins (survivin and BCL2,) and down regulates the activities of P-glycoprotein in drug sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. Similarly, it also exerts alteration in P13K, AKT, p21, MMP-2 &-9, and phosphorylated-AKT expressions. The current review highlights the anticancer and chemo-preventive perspectives of gambogic acid and its mechanistic role against human and animal cancers.

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Gambogic acid-loaded magnetic Fe3O4 nanoparticles inhibit Panc-1 pancreatic cancer cell proliferation and migration by inactivating transcription factor ETS1

Cited by 21 publications

References 32 publications

Onivyde for the therapy of multiple solid tumors

Onivyde for the therapy of multiple solid tumors

Gambogic acid sensitizes gemcitabine efficacy in pancreatic cancer by reducing the expression of ribonucleotide reductase subunit-M2 (RRM2)

Gambogic Acid as Anticancer Agent: A Review

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