Related Experiment Video
Updated: May 5, 2026
Delivery of Therapeutic Agents Through Intracerebroventricular ICV and Intravenous IV Injection in Mice
Published on: October 3, 2011
Biosacetalin (1,1-Diethoxyethane) Prolongs Survival and Alleviates Cachexia in the NSG Mice Bearing Neuroblastoma
Dhiraj Kumar Sah1,2, Thang Nguyen Huu1,2, Jin Myung Choi3
1Department of Biochemistry, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
Abstract:
Neuroblastoma remains a formidable pediatric malignancy characterized by profound metabolic plasticity and limited therapeutic responsiveness in high-risk disease. Emerging evidence positions the interplay between Reactive Oxygen Species (ROS) and the metabolic sentinel AMP-activated protein kinase (AMPK) as a critical regulator of tumor metabolic stress and apoptotic susceptibility, with additional implications in the systemic pathology of Cancer Cachexia. Building on our previous work demonstrating that 1,1-Diethoxyethane (1,1-DEE; Biosacetalin), a volatile aroma compound inhibits mitochondrial complex I, induces ROS production, and activates AMPK-PGC1α-mediated mitochondrial biogenesis accompanying enhancement of aerobic respiration, leading to anti-Warburg effect. We identify 1,1-DEE as a previously unrecognized metabolic modulator with potent antitumor activity. 1,1-DEE triggers ROS-induced AMPK activation, leading to apoptotic elimination of neuroblastoma cells (SH-SY5Y), robust suppression of tumor growth, and significant prolongation of survival (median survival 77 days) in tumor-bearing NSG mice. Strikingly, 1,1-DEE simultaneously alleviates cancer-associated cachexia by preserving body weight. Mechanistically, our findings reveal a ROS-AMPK-centered signaling axis through which 1,1-DEE integrates tumor-selective cytotoxicity with systemic metabolic protection, highlighting a unified therapeutic strategy for targeting both tumor progression and cachexia in neuroblastoma.
Insights
1,1-Diethoxyethane (1,1-DEE) shows potent anti-neuroblastoma activity by activating AMP-activated protein kinase (AMPK) and Reactive Oxygen Species (ROS). This compound also combats cancer cachexia, offering a dual therapeutic approach.
Area of Science:
- Oncology
- Metabolic pathways
- Mitochondrial function
Background:
- Neuroblastoma is a challenging pediatric cancer with high-risk disease showing limited treatment options.
- Metabolic plasticity and the ROS-AMPK axis are key in tumor progression and cachexia.
- Previous work showed 1,1-Diethoxyethane (1,1-DEE) modulates mitochondrial function and induces ROS.
Purpose of the Study:
- To investigate 1,1-DEE as a metabolic modulator for neuroblastoma treatment.
- To explore the role of the ROS-AMPK axis in 1,1-DEE's anti-tumor effects.
- To assess 1,1-DEE's impact on cancer-associated cachexia.
Main Methods:
- In vitro studies using neuroblastoma cell lines (SH-SY5Y).
- In vivo studies using tumor-bearing NSG mice models.
- Analysis of mitochondrial complex I activity, ROS production, AMPK activation, and PGC1α signaling.
- Assessment of tumor growth, survival rates, and body weight changes.
Main Results:
- 1,1-DEE inhibits mitochondrial complex I, increases ROS, and activates AMPK, leading to enhanced aerobic respiration and an anti-Warburg effect.
- 1,1-DEE induced apoptosis in neuroblastoma cells and significantly suppressed tumor growth in mice.
- Treatment with 1,1-DEE prolonged median survival to 77 days and alleviated cancer cachexia by preserving body weight.
Conclusions:
- 1,1-DEE is a novel metabolic modulator with significant anti-neuroblastoma efficacy.
- The ROS-AMPK signaling axis mediates 1,1-DEE's tumor-selective cytotoxicity and systemic metabolic protection.
- 1,1-DEE presents a promising unified therapeutic strategy for neuroblastoma and associated cachexia.
