Polyphyllin D Shows Anticancer Effect through a Selective Inhibition of Src Homology Region 2-Containing Protein Tyrosine Phosphatase-2 (SHP2)
| Autor: | Se Jeong Kwon, Dohee Ahn, Sang J. Chung, Hyo Jin Kang, Hyun-Mo Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
natural products
PTPN6 Pharmaceutical Science Antineoplastic Agents Protein Tyrosine Phosphatase Non-Receptor Type 11 Protein tyrosine phosphatase Diosgenin Jurkat cells Analytical Chemistry lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound Jurkat Cells 0302 clinical medicine lcsh:Organic chemistry Drug Discovery Humans src homology region 2-domain-containing phosphatase-1 (SHP-1) Physical and Theoretical Chemistry Enzyme Inhibitors protein tyrosine phosphatase (PTP) Cytotoxicity Oleanolic acid 030304 developmental biology Cell Proliferation polyphyllin D 0303 health sciences Kinase Chemistry Communication Organic Chemistry leukemia Saponins Molecular biology src homology region 2-containing protein tyrosine phosphatase-2 (SHP2) Chemistry (miscellaneous) 030220 oncology & carcinogenesis Molecular Medicine Phosphorylation Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Molecules, Vol 26, Iss 848, p 848 (2021) Molecules |
| ISSN: | 1420-3049 |
| Popis: | Natural products have continued to offer tremendous opportunities for drug development, as they have long been used in traditional medicinal systems. SHP2 has served as an anticancer target. To identify novel SHP2 inhibitors with potential anticancer activity, we screened a library containing 658 natural products. Polyphyllin D was found to selectively inhibit SHP2 over SHP1, whereas two other identified compounds (echinocystic acid and oleanolic acid) demonstrated dual SHP1 and SHP2 inhibition. In a cell-based assay, polyphyllin D exhibited cytotoxicity in Jurkat cells, an acute lymphoma leukemia cell line, whereas the other two compounds were ineffective. Polyphyllin D also decreased the level of phosphorylated extracellular signal-regulated kinase (p-ERK), a proliferation marker in Jurkat cells. Furthermore, knockdown of protein tyrosine phosphatase (PTP)N6 (SHP1) or PTPN11 (SHP2) decreased p-ERK levels. However, concurrent knockdown of PTPN6 and PTPN11 in Jurkat cells recovered p-ERK levels. These results demonstrated that polyphyllin D has potential anticancer activity, which can be attributed to its selective inhibition of SHP2 over SHP1. |
| Databáze: | OpenAIRE |
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