Ellagic acid, extracted from Sanguisorba officinalis, induces G1 arrest by modulating PTEN activity in B16F10 melanoma cells.

Ellagic acid, extracted from Sanguisorba officinalis, induces G1 arrest by modulating PTEN activity in B16F10 melanoma cells.

Publication date: Sep 08, 2019

In Chinese medicine, herbal medicine is commonly used to treat individuals suffering from many types of diseases. We thus expected that some herbal medicines would contain promising compounds for cancer chemotherapy. Indeed, we found that Sanguisorba officinalis extracts strongly inhibit the growth of B16F10 melanoma cells, and we identified ellagic acid (EA) as the responsible ingredient. B16F10 cells treated with EA exhibited strong G1 arrest accompanied by accumulation of p53, followed by inactivation of AKT. Addition of a PTEN inhibitor, but not a p53 inhibitor, abrogated the EA-induced AKT inactivation and G1 arrest. The PTEN inhibitor also diminished EA-induced p53 accumulation. Furthermore, EA apparently increased the protein phosphatase activity of PTEN, as demonstrated by the reduced phosphorylation level of FAK, a protein substrate of PTEN. Furthermore, an in vitro PTEN phosphatase assay on PIP3 showed the direct modulation of PTEN activity by EA. These results suggest that EA functions as an allosteric modulator of PTEN, enhancing its protein phosphatase activity while inhibiting its lipid phosphatase activity. It is notable that a combination of EA and cisplatin, a widely used chemotherapy agent, dramatically enhanced cell death in B16F10 cells, suggesting a promising strategy in chemotherapy. This article is protected by copyright. All rights reserved.

Tan, Y.H., Shudo, T., Yoshida, T., Sugiyama, Y., Si, J.Y., Tsukano, C., Takemoto, Y., and Kakizuka, A. Ellagic acid, extracted from Sanguisorba officinalis, induces G1 arrest by modulating PTEN activity in B16F10 melanoma cells. 24050. 2019 Genes Cells.

Concepts Keywords
AKT Diseases
Allosteric Modulator Growth B16F10 melanoma
Assay Chemotherapy
Chemotherapy Herbal medicines
Chinese Medicine Branches of biology
Cisplatin Tumor suppressor genes
Ellagic Acid PTEN
FAK Signal transduction
Inhibitor Protein kinase B
Lipid P53
Melanoma Phosphatidylinositol (3,4,5)-trisphosphate
Modulation MTOR
P53 Chemotherapy
Phosphatase
Phosphorylation
PIP3
PTEN
Sanguisorba Officinalis
Substrate

Semantics

Type Source Name
drug DRUGBANK Cisplatin
gene UNIPROT PTK2
gene UNIPROT PTEN
gene UNIPROT TP53
disease DOID cancer
disease MESH growth
disease MESH cancer
disease MESH suffering
disease DOID melanoma
pathway BSID Melanoma
disease MESH melanoma
drug DRUGBANK Ellagic Acid

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