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