Study of the Anticancer Potential of Plant Extracts Using Liver Tumor Microphysiological System

Background: Plants have been considered a vital source of modern pharmaceutics since the paleolithic age. Contemporary chemotherapeutic drugs for cancer therapy are chemical entities sourced from plants. However, synthetic drugs or their derivatives come with severe to moderate side effects for human health. Hence, the quest to explore and discover plant-based novel anticancer drugs is ongoing. Anticancer activities are the primary method to estimate the potential and efficacy of an extract or compound for drug discovery. However, traditional in vitro anticancer activity assays often show poor efficacy due to the lack of in-vivo-like cellular environment. In comparison, the animal-based in vivo assays lack human genetic makeup and have ethical concerns. Aim: This study aimed to overcome the limitations of traditional cell-culture-based anticancer assays and find the most suitable assay for anticancer activity of plant extracts. We first reported utilizing a liver tumor microphysiological system in the anticancer effect assessment of plant extracts. Methodology: Methanolic extracts of Acer cappadocicum Gled were used to assess anticancer activity against liver tumor microphysiological system (MPS), and cell viability, liver function tests, and antioxidant enzyme activities were performed. Additionally, an embedded transepithelial electrical resistance sensor was utilized for the real-time monitoring of the liver tumor MPS. The results were also compared with the traditional cell culture model. Results: The study demonstrated the superiority of the TEER sensor-based liver tumor MPS by its better anticancer activity based on cell viability and biomarker analysis compared to the traditional in vitro cell culture model. The anticancer effects of the plant extracts were successfully observed in real time, and methanolic extracts of Acer cappadocicum Gled increased the alanine transaminase and aspartate aminotransferase secretion, which may reveal the different mechanisms of these extracts and suggest a clue for the future molecular study of the anticancer pathways. Conclusion: Our results show that the liver tumor microphysiological system could be a better platform for plant-based anticancer activity assessment than traditional cell culture models.