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Degalactotigonin, a Steroidal Glycoside from Solanum nigrum, Induces Apoptosis and Cell Cycle Arrest via Inhibiting the EGFR Signaling Pathways in Pancreatic Cancer Cells.

Abstract
Degalactotigonin (1) and three other steroidal compounds solasodine (2), O-acetyl solasodine (3), and soladulcoside A (4) were isolated from the methanolic extract of Solanum nigrum, and their chemical structures were elucidated by spectroscopic analyses. The isolated compounds were evaluated for cytotoxic activity against human pancreatic cancer cell lines (PANC1 and MIA-PaCa2) and lung cancer cell lines (A549, NCI-H1975, and NCI-H1299). Only degalactotigonin (1) showed potent cytotoxicity against these cancer cell lines. Compound 1 induced apoptosis in PANC1 and A549 cells. Further study on its mechanism of action in PANC1 cells demonstrated that 1 significantly inhibited EGF-induced proliferation and migration in a concentration-dependent manner. Treatment of PANC1 cells with degalactotigonin induced cell cycle arrest at G0/G1 phase. Compound 1 induced downregulation of cyclin D1 and upregulation of p21 in a time- and concentration-dependent manner and inhibited EGF-induced phosphorylation of EGFR, as well as activation of EGFR downstream signaling molecules such as Akt and ERK.
AuthorsHoang Le Tuan Anh, Phuong Thao Tran, Do Thi Thao, Duong Thu Trang, Nguyen Hai Dang, Pham Van Cuong, Phan Van Kiem, Chau Van Minh, Jeong-Hyung Lee
JournalBioMed research international (Biomed Res Int) Vol. 2018 Pg. 3120972 ( 2018) ISSN: 2314-6141 [Electronic] United States
PMID30643798 (Publication Type: Journal Article)
Chemical References
  • Saponins
  • Steroids
  • degalactotigonin
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
Topics
  • A549 Cells
  • Apoptosis (drug effects)
  • Cell Cycle Checkpoints (drug effects)
  • ErbB Receptors (metabolism)
  • Humans
  • MAP Kinase Signaling System (drug effects)
  • Pancreatic Neoplasms (drug therapy, metabolism, pathology)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Saponins (chemistry, pharmacology)
  • Solanum nigrum (chemistry)
  • Steroids (chemistry, pharmacology)

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