Preprint Article Version 1 This version is not peer-reviewed

Use of an Intelligent Natural Language System to Identify Cilia-Promoting Drugs that Suppress Cancer Cell Replication

Version 1 : Received: 13 October 2024 / Approved: 14 October 2024 / Online: 14 October 2024 (12:27:56 CEST)

How to cite: Fu, S. H.; Limerick, A.; Park, C.; Shah, N.; Zhang, Y.; Abounader, R.; Fu, Z. Use of an Intelligent Natural Language System to Identify Cilia-Promoting Drugs that Suppress Cancer Cell Replication. Preprints 2024, 2024101036. https://doi.org/10.20944/preprints202410.1036.v1 Fu, S. H.; Limerick, A.; Park, C.; Shah, N.; Zhang, Y.; Abounader, R.; Fu, Z. Use of an Intelligent Natural Language System to Identify Cilia-Promoting Drugs that Suppress Cancer Cell Replication. Preprints 2024, 2024101036. https://doi.org/10.20944/preprints202410.1036.v1

Abstract

The primary cilium, the cell’s sensory and signaling antenna, is a dynamic cellular organelle during the cell cycle. It is resorbed before cells enter mitosis and reformed after cells exit mitosis, and as such acts as a structural barrier to mitosis. Cancer cells that undergo rapid cell cycle and replication have a low ciliation rate. Therefore, promoting cilia formation and elongation and thereby reducing their rates of retraction hold the key to blocking cell entry into mitosis and slowing down cancer cell replication. To perform a comprehensive and efficient literature search on drugs that can promote ciliogenesis, we developed an intelligent process that integrates the GPT-3.5 application programming interface (API) into a PubMed scraper that we coded, enabling the large language model (LLM) to directly query articles for predefined user questions. Among the top candidates identified are two FDA-approved drugs, Alvocidib and Alisertib, that showed strong potential to induce cilia formation and elongation. We first confirmed that these drugs can effectively increase the ciliation rate and the cilia length of DAOY medulloblastoma cells. We then applied Alvocidib and Alisertib individually or in combination to DAOY medulloblastoma and A549 lung cancer cells and observed a statistically significant decrease in the number of viable cells. These results demonstrated the potential of using cilia-promoting drugs to suppress cancer cell replication. Additionally, it shows the massive benefits of integrating accessible large language models to conduct sweeping, rapid, and accurate literature searches.

Keywords

Natural Language Processing (NLP); Large Language Model (LLM); primary cilia; ciliogenesis; Alvocidib; Alisertib; cancer

Subject

Biology and Life Sciences, Cell and Developmental Biology

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