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Alternative Models for Anticancer Drug Discovery From Natural Products Using Binary Tumor-Microenvironment-on-a-Chip
Youngwon Kim1,2, Si Hyeon Chae3, Dahae Lee4
1School of Mechanical Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 13722, Republic of Korea.
Abstract:
The efficacy evaluation of anticancer drugs derived from natural products has traditionally relied on animal models, highlighting the need for more efficient preclinical assessment platforms. In this study, a binary tumor-microenvironment-on-a-chip (T-MOC) system is introduced to assess the therapeutic potential of illudin S and roridin E, two cytotoxic compounds derived from Omphalotus japonicus and Podostroma cornu-damae, respectively. The binary T-MOC model integrates independently developed vascular and invasive ductal carcinoma compartments, effectively mimicking in vivo drug delivery barriers and physiological dynamics. Using this model, illudin S demonstrates strong anticancer effects but exhibits high toxicity, particularly in the lung and liver, indicating a narrow therapeutic window. Roridin E demonstrates potent activity at low concentrations but exhibits high toxicity, especially in the liver and skin. Additionally, morphological analysis is performed to predict drug delivery and distribution characteristics, revealing anisotropic remission and the influence of microenvironmental factors on drug response. This study underscores the potential of the binary T-MOC system as an alternative platform for anticancer drug evaluation, enabling efficient preclinical validation while reducing reliance on animal models.
Insights
A novel tumor-microenvironment-on-a-chip (T-MOC) system offers efficient preclinical anticancer drug evaluation. This platform assesses natural compounds illudin S and roridin E, revealing their efficacy and toxicity profiles, reducing animal model reliance.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Cancer Research
Background:
- Traditional anticancer drug evaluation relies on animal models, which are inefficient and ethically concerning.
- There is a critical need for advanced preclinical platforms to assess drug efficacy and toxicity more effectively.
- Natural products are a promising source of novel anticancer agents, but their development requires robust assessment tools.
Purpose of the Study:
- To introduce and validate a binary tumor-microenvironment-on-a-chip (T-MOC) system for evaluating anticancer drugs.
- To assess the therapeutic potential and toxicity of illudin S and roridin E using the developed T-MOC model.
- To explore the predictive capabilities of the T-MOC system for drug delivery, distribution, and microenvironmental influences.
Main Methods:
- Development of a binary T-MOC system integrating vascular and invasive ductal carcinoma compartments.
- Assessment of illudin S and roridin E, cytotoxic compounds from Omphalotus japonicus and Podostroma cornu-damae, respectively.
- Morphological analysis to predict drug delivery, distribution, and microenvironmental effects on drug response.
Main Results:
- Illudin S showed strong anticancer effects but significant lung and liver toxicity, indicating a narrow therapeutic window.
- Roridin E exhibited potent activity at low doses but high toxicity, particularly in the liver and skin.
- The T-MOC model revealed anisotropic remission and the impact of microenvironmental factors on drug response.
Conclusions:
- The binary T-MOC system serves as a promising alternative to animal models for preclinical anticancer drug evaluation.
- This platform facilitates efficient validation of natural product-derived anticancer agents like illudin S and roridin E.
- The T-MOC system aids in understanding drug delivery barriers, toxicity, and microenvironmental influences, optimizing drug development.
