Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma

Area of Science:

• Oncology
• Pharmacology
• Plant-derived medicine

Background:

• Ewing sarcoma is a prevalent pediatric bone cancer with poor outcomes.
• European mistletoe (Viscum album L.) has shown anticancer properties, but its potential against Ewing sarcoma is unexplored.
• Commercial mistletoe extracts lack insoluble triterpenes, potentially limiting their efficacy.

Purpose of the Study:

• To investigate the efficacy of a combined Viscum album L. extract (viscumTT) against Ewing sarcoma.
• To evaluate the synergistic effects of aqueous (viscum) and triterpene (TT) mistletoe extracts.
• To explore the underlying mechanisms of viscumTT-induced apoptosis in Ewing sarcoma cells.

Main Methods:

• In vitro, ex vivo, and in vivo studies using Ewing sarcoma cell lines and patient-derived xenografts.
• Treatment with aqueous mistletoe extract (viscum), triterpene extract (TT), and their combination (viscumTT).
• Analysis of apoptosis pathways, regulatory proteins (CLSPN, MCL1, BIRC5, XIAP), and tumor growth.

Main Results:

• Viscum extract inhibited proliferation and induced apoptosis in a dose-dependent manner.
• The viscumTT combination demonstrated synergistic effects, significantly enhancing apoptosis.
• ViscumTT treatment activated both intrinsic and extrinsic apoptotic pathways and showed strong antitumor activity in vivo.

Conclusions:

• ViscumTT effectively targets Ewing sarcoma by inducing apoptosis through multiple pathways.
• The combination therapy downregulates key anti-apoptotic proteins, shifting the balance towards cell death.
• ViscumTT represents a promising adjuvant therapy option for pediatric Ewing sarcoma patients.