Cytotoxic effects of neolignans from Saururus cernuus (Saururaceae) against prostate cancer cells.

Abstract

In this study, five neolignans were isolated from Saururus cernuus-threo-dihydroguaiaretic acid (1), threo-austrobailignan-6 (2), threo-austrobailignan-5 (3), verrucosin (4), and saucernetin (5)-and have their cytotoxic effects evaluated in prostate cancer cell lines (PC3 and DU145). Initially, using an in silico approach, tested compounds were predicted to be absorbed by the gastrointestinal tract, be able to permeate the blood-brain barrier and did not show any alert in PAINS (pan-assay structures interference). In vitro assays showed that compounds 2, 4, and 5 reduced cell viability of DU145 cell line at 100 μmol/L after 48 h while compounds 1 and 3 showed to be inactive at the same conditions. Furthermore, compounds 4 and 5 reduced cell number as early as in 24 h at 50 μmol/L and compound 2 showed effects at 100 μmol/L in 24 h against both cancer cell lines PC3 and DU145. Studies using flow cytometry were conducted and indicated that compound 4 induced strong necrosis and apoptosis whereas compound 5 induced strong necrosis. Otherwise, less active compound 2 did not show evidence of induction of apoptosis or necrosis, suggesting that its mechanism of action involves inhibition of cell proliferation. In conclusion, compounds 4 and 5 have been shown to be promising cytotoxic agents against prostate cancer cell lines and can be used as a starting point for the development of new drugs for the treatment of prostate cancer.

• Authors: Nicholas Pietro Agulha Toneto, Juliana Ribeiro de Brito, Patricia Sartorelli, Miriam Uemi, Marina de Monroe Gonçalves, Ileana Gabriela Sánchez de Rubio, João Henrique Ghilardi Lago, Rodrigo Esaki Tamura
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 101 Issue 6 Pg. 1299-1306 (06 2023) ISSN: 1747-0285 [Electronic] England
• PMID: 36752700 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 John Wiley & Sons Ltd.

Chemical References

• Lignans
• Antineoplastic Agents

Topics

• Male
• Humans
• Saururaceae (chemistry)
• Lignans (pharmacology, therapeutic use)
• Antineoplastic Agents (pharmacology)
• Prostatic Neoplasms (drug therapy)
• Apoptosis
• Cell Line, Tumor
• Necrosis (drug therapy)