Studies on the mechanism of action of frondoside A in pancreatic cancer

Shemaili, J. Al; Parekh, K.; Thomas, S.A.; Kelly, D.; Ding, Xian; Attoub, Samir; Collin, S.P.; Adrian, Thomas E.

doi:10.1016/j.pan.2012.12.097

Cited by 3 publications

(3 citation statements)

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“…Downregulated genes included E2F1, cyclin A2, cdc20, cdc21, cdc45, and cdc47, all of which play important roles in DNA replication and cell cycle control [ 54 ]. Upregulated genes included fatty acid binding protein 3 (FABP3), growth and development factor 15 (GDF15), p21 WAF-1 (which has been shown to be upregulated in multiple studies as outlined above), repressor of E1A, dual-specificity phosphatase, and death-associated protein kinase-1 [ 54 ]. Attention was focused on GDF15 and FABP3 [ 54 ].…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

“…Upregulated genes included fatty acid binding protein 3 (FABP3), growth and development factor 15 (GDF15), p21 WAF-1 (which has been shown to be upregulated in multiple studies as outlined above), repressor of E1A, dual-specificity phosphatase, and death-associated protein kinase-1 [ 54 ]. Attention was focused on GDF15 and FABP3 [ 54 ]. GDF15 belongs to the transforming growth factor superfamily that plays a role in regulating inflammatory and apoptotic pathways during tissue injury, and mediates apoptosis induction in response to NSAIDS.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

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The Anti-Cancer Effects of Frondoside A

Adrian

Collin

2018

Marine Drugs

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Frondoside A is a triterpenoid glycoside from the Atlantic Sea Cucumber, Cucumaria frondosa. Frondoside A has a broad spectrum of anti-cancer effects, including induction of cellular apoptosis, inhibition of cancer cell growth, migration, invasion, formation of metastases, and angiogenesis. In cell lines and animal models studied to date, the anti-cancer effects of the compound are seen in all solid cancers, lymphomas, and leukemias studied to date. These effects appear to be due to potent inhibition of p21-activated kinase 1 (PAK1), which is up-regulated in many cancers. In mouse models, frondoside A has synergistic effects with conventional chemotherapeutic agents, such as gemcitabine, paclitaxel, and cisplatin. Frondoside A administration is well-tolerated. No side effects have been reported and the compound has no significant effects on body weight, blood cells, or on hepatic and renal function tests after long-term administration. Frondoside A may be valuable in the treatment of malignancies, either as a single agent or in combination with other therapeutic modalities.

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Section: Mechanisms Of Actionmentioning

confidence: 99%

Section: Mechanisms Of Actionmentioning

confidence: 99%

The Anti-Cancer Effects of Frondoside A

Adrian

Collin

2018

Marine Drugs

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“…Based on our molecular investigations, the free energies of Frondoside A and the critical proteins were observed to be below -5 kcal/mol, indicating favorable binding of the aforementioned active ingredients to their respective targets. Studies have shown that Frondoside A can down-regulate CDC20 gene expression, which inhibits the proliferation and migration of cancer cells and promotes cycle arrest and cell apoptosis (79,80). In addition, Zhang and colleagues have shown that TOP2A deletion can significantly inhibit the proliferation and migration of cancer cells and induce cell apoptosis (81-83).…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor target screening of sea cucumber saponin Frondoside A: a bioinformatics and molecular docking analysis

Liu,

Zhang,

Lin

et al. 2023

Front. Oncol.

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Cancer remains the leading cause of death worldwide. In spite of significant advances in targeted and immunotherapeutic approaches, clinical outcomes for cancer remain poor. The aim of the present study was to investigate the potential mechanisms and therapeutic targets of Frondoside A for the treatment of liver, pancreatic, and bladder cancers. The data presented in our study demonstrated that Frondoside A reduced the viability and migration of HepG2, Panc02, and UM-UC-3 cancer cell in vitro. Moreover, we utilized the GEO database to screen and identify for differentially expressed genes (DEGs) in liver, pancreatic, and bladder cancers, which resulted in the identification of 714, 357, and 101 DEGs, respectively. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation were performed using the Metascape database for DEGs that were significantly associated with cancer development. The protein-protein interaction (PPI) networks of the identified DEGs in liver, pancreatic, and bladder cancers were analyzed using Cytoscape 3.9.0 software, and subsequently identified potential key genes that were associated with these networks. Subsequently, their prognostic values were assessed by gene expression level analysis and Kaplan-Meier survival analysis (GEPIA). Furthermore, we utilized TIMER 2.0 to investigate the correlation between the expression of the identified key gene and cancer immune infiltration. Finally, molecular docking simulations were performed to assess the affinity of Frondoside A and key genes. Our results showed a significant correlation between these DEGs and cancer progression. Combined, these analyses revealed that Frondoside A involves in the regulation of multiple pathways, such as drug metabolism, cell cycle in liver cancer by inhibiting the expression of CDK1, TOP2A, CDC20, and KIF20A, and regulates protein digestion and absorption, receptor interaction in pancreatic cancer by down-regulation of ASPM, TOP2A, DLGAP5, TPX2, KIF23, MELK, LAMA3, and ANLN. While in bladder cancer, Frondoside A regulates muscle contraction, complement and coagulation cascade by increase FLNC expression. In conclusion, the present study offers valuable insights into the molecular mechanism underlying the anticancer effects of Frondoside A, and suggests that Frondoside A can be used as a functional food supplement or further developed as a natural anti-cancer drug.

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