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.

<p>Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer</p>

“…Pancreatic cancer is one of the major causes of cancer-related mortality and is the 12th most common cancer in human worldwide. 1,2 The 5-year overall survival rates of pancreatic cancer remain less than 6%, indicating that pancreatic cancer is one of the deadliest forms of cancer. 3 Chronic pancreatitis, smoking, obesity, diabetes mellitus are several risk factors that seem to be associated with pancreatic cancer.…”

Diversity and Antimicrobial Activity of Culturable Fungal Endophytes in Solanum mauritianum

“…Fungal endophytes in Panax ginseng have been investigated for their ability to produce ginsenosides [11], and the steroidal alkaloid Solamargine from fungal endophytes of Solanum nigrum L. [12]. Solamargine has been reported to be cytotoxic and has been experimentally attempted on various cancer cell lines (related to skin, breast and liver) [13]. In this study, efforts have been made to isolate endophytic fungi inhibiting a range of pathogenic bacteria including Mycobacterium bovis.…”

Probing the Antitumor Mechanism of Solanum nigrum L. Aqueous Extract against Human Breast Cancer MCF7 Cells

“…Various active ingredients of S. nigrum L. have been isolated and characterized for their antitumor functions. For example, an isolated glycoprotein modulated the function of transcriptional factors NF-κB and AP-1 in human breast cancer MCF7 cells [24], degalactotigonin, a steroidal glycoside, suppressed the EGFR signaling pathway in pancreatic cancer cells [25] and the Hedgehog/GLI1 signaling pathway in osteosarcoma [21], and α-solanine inhibited the epithelial-mesenchymal transition in human prostate cancer cells [26]. However, the antitumor MOA of S. nigrum L. aqueous or ethanol extract is still far from clear.…”