Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity

Hamdoun, Sami; Efferth, Thomas

doi:10.18632/oncotarget.16626

Cited by 49 publications

(42 citation statements)

References 48 publications

(62 reference statements)

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“…Collectively, the results of the present study indicated that GA suppressed the development of RCC. These results were consistent with previous studies demonstrating that GA plays an inhibitory biological role in cancer (12)(13)(14)(15)25). However, the biological effect of GA on RCC was observed at high concentrations of GA in vitro and it is uncertain whether this concentration would be possible in vivo.…”

Section: Discussionsupporting

confidence: 92%

“…Extracts from natural plants are becoming an increasingly popular strategy to identify novel antitumor compounds (23,24). Recently, several studies have reported that GA displays promising antitumor activities (12)(13)(14)(15). Therefore, identification of the regulatory mechanism of GA in tumorigenesis would provide valuable insight for the treatment of malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…GA suppresses tumor growth and invasion via various signaling pathways, including the hepatocyte growth factor/c-Met signaling pathway in hepatocellular carcinoma (12), the protein kinase AMP-activated catalytic subunit α2 signaling pathway in colon cancer (13), the NF-κB signaling pathway in breast cancer (14) and the PI3K/Akt/mTOR signaling pathway in lung cancer (15). A number of studies have reported that, in addition to inducing cell cycle arrest, GA also increases apoptosis in colon cancer and hepatocellular carcinoma (26,27).…”

Section: Discussionmentioning

confidence: 99%

“…GA has been reported to display a wide range of bioactive properties, including antimicrobial, antivirus and molluscicidal activities (11). Accumulating evidence has demonstrated that several monomer structures of GA (C13:0, C15:0 and C17:1) exert antitumor activity in a number of human malignancies, including hepatocellular carcinoma as well as colon, breast and lung cancer (12)(13)(14)(15). However, to the best of our knowledge, no previous study has been conducted to investigate the pharmacological effect of GA in RCC.…”

Section: Introductionmentioning

confidence: 99%

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Ginkgolic acid inhibits the growth of renal cell carcinoma cells via inactivation of the EGFR signaling pathway

Zhu

Na²,

Huang³

et al. 2020

Exp Ther Med

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Renal cell carcinoma (RCC) is one of the most common urological malignancies occurring in adult human kidneys worldwide. Recent research on antitumor drugs has focused on plant extracts, a class of compounds that play critical roles in cancer treatment. The present study aimed to investigate the potential antitumor effect of ginkgolic acid (GA) in RCC. Transwell invasion assay, cell counting kit-8 assay and flow cytometry were used to measure cell migration, cell viability and apoptosis, respectively. A network pharmacology approach was applied to identify pathway information, combining molecular docking techniques to screen for key target information. In the present study, GA inhibited the viability and proliferation of RCC cells (786-O and A498), both in vitro and in vivo, via G 1 arrest. GA also reduced RCC cell invasion and migration. In addition, the epidermal growth factor receptor (EGFR) was identified as a critical target protein of GA, which significantly inactivated EGFR signaling in RCC (P<0.05). Collectively, the present study provided evidence that GA exerts its anticancer function by directly targeting the EGFR signaling pathway, revealing the potential of GA therapy for RCC.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ginkgolic acid inhibits the growth of renal cell carcinoma cells via inactivation of the EGFR signaling pathway

Zhu

Na²,

Huang³

et al. 2020

Exp Ther Med

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“…C15:1 is one of the most abundant GAs in Ginkgo biloba L. extract (14). Recently, a number of studies have indicated the anticancer activity of GA in a variety of cancer types and the less toxic reaction on non-cancerous cells (15)(16)(17)(18). However, to the best of our knowledge, whether GA can inhibit the invasion of liver cancer cells and the underlying mechanisms remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Ginkgolic acid suppresses the invasion of HepG2 cells via downregulation of HGF/c‑Met signaling

Meng

Zhang

et al. 2018

Oncol Rep

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Liver cancer is one of the most devastating types of cancer worldwide. Despite years of improvements in treatment, the prognosis of patients with this type of malignancy remains poor due to frequent recurrence and metastasis after surgical resection. Ginkgolic acid (GA) is a botanical drug extracted from the seed coat of Ginkgo biloba L. that possesses a wide range of bioactive properties. However, to the best of our knowledge, whether GA can inhibit the invasion of liver cancer cells and the underlying mechanisms remains unknown. The aim of the present study was to investigate the effects of GA on the migration and invasion abilities of liver cancer cells and the underlying molecular mechanism. The results revealed that GA suppressed the migration and invasion abilities of HepG2 cells. In addition, GA treatment inhibited the expression of invasion-related molecules (MMP-2 and MMP-9) and prevented the epithelial-mesenchymal transition (EMT) of HepG2 cells. Further experiments revealed that GA-reduced hepatocyte growth factor (HGF) production and suppressed c-Met phosphorylation may be the underlying mechanisms. Exogenous recombinant HGF supplementation improved the cell invasion ability impaired by GA. Moreover, the in vivo experiment revealed that GA inhibited the tumor growth of liver cancer and prevented EMT. Collectively, these data indicated that GA effectively suppressed the invasion and EMT of HepG2 cells via downregulation of HGF/c-Met signaling, thus GA may serve as a novel chemotherapeutic agent for the

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Ubiquitin, SUMO, and Nedd8 as Therapeutic Targets in Cancer

Gâtel¹,

Piechaczyk²,

Bossis³

2020

Advances in Experimental Medicine and Biology

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Ubiquitin defines a family of approximately 20 peptidic post-translational modifiers collectively called the Ubiquitin-like (UbLs). They are conjugated to thousands of proteins, modifying their function and fate in many ways. Dysregulation of these modifications has been implicated in a variety of pathologies, in particular cancer. Ubiquitin, SUMO (-1 to-3) and Nedd8 are the bestcharacterized UbLs. They have been involved in the regulation of the activity and/or the stability of diverse components of various oncogenic or tumor suppressor pathways. Moreover, the dysregulation of enzymes responsible for their conjugation/deconjugation has also been associated with tumorigenesis and cancer resistance to therapies. The UbL system therefore constitutes an attractive target for developing novel anticancer therapeutic strategies. Here, we review the roles and dysregulations of Ubiquitin-, SUMO-and Nedd8 pathways in tumorigenesis, as well as recent advances in the identification of small molecules targeting their conjugating machineries for potential application in the fight against cancer. 4 most substrates being constantly modified and demodified. Deconjugation is carried out by isopeptidases, which cleave the isopeptide bonds between UbLs and target lysines. This allows UbLs, which are highly stable polypeptides, to be recycled and reconjugated to other proteins. Some isopeptidases are also involved in the proteolytic maturation of UbLs, which are synthetized in the form of precursors displaying extra amino-acids at their C-termini. Similar to E3s, isopeptidases show substrate specificity or, at least, preference for particular chain linkages [9]. Concerning the SUMO pathway, deSUMOylases, such as SENP6 and SENP7, preferentially cleave SUMO-2 chains, whilst others, such as SENP-1 and SENP-2, rather deconjugate SUMO bound to target proteins [10]. Some deSUMOylases such as SENP-3, SENP-5 and USPL1 have preference for SUMO-2 over SUMO-1 [11, 12]. The consequences of UbL conjugation are numerous. They depend on the UbL type, possibly the nature of UbL chains formed and, obviously, the substrate. As they have been reviewed extensively elsewhere [3, 13-15], only the main physiological roles of Ubiquitylation, SUMOylation and Neddylation are considered hereafter. The biological outcomes of Ubiquitin conjugation are highly dependent on the chain linkage types, which, due to their diversity and complexity, create the so-called "Ubiquitin code" [14]. The most abundant and best-characterized Ubiquitin chains are long K48-linked ones (>4 Ubiquitins). They constitute a protein degradation signal recognized by the 26S proteasome, which is the main cell proteolytic machinery [16-18]). This discovery led Avram Hershko, Irwin Rose an Aaron Ciechanover to be awarded the Nobel Prize in 2004. It is, however, important to keep in mind that K48-linked Ubiquitin chains can also be involved in signaling events and transcription regulation not involving protein destruction [19-21]. K63-linked chains are bestknown as involved in protein-protei...

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Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity

Cited by 49 publications

References 48 publications

Ginkgolic acid inhibits the growth of renal cell carcinoma cells via inactivation of the EGFR signaling pathway

Ginkgolic acid inhibits the growth of renal cell carcinoma cells via inactivation of the EGFR signaling pathway

Ginkgolic acid suppresses the invasion of HepG2 cells via downregulation of HGF/c‑Met signaling

Ubiquitin, SUMO, and Nedd8 as Therapeutic Targets in Cancer

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