김태정 (한국과학기술연구원, UST) | 한빛사논문 > 한빛사

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조회76

한국과학기술연구원, UST

Exp. Mol. Med., May 01 2025, | https://doi.org/10.1038/s12276-025-01444-x Cannabidiol potentiates p53-driven autophagic cell death in non-small cell lung cancer following DNA damage: a novel synergistic approach beyond canonical pathways

Youngsic Jeon ^1,7, Taejung Kim ^1,2,7, Hyukjoon Kwon ¹, Young Nyun Park ³, Tae-Hyung Kwon ⁴, Min Hong⁴, Kyung-Chul Choi ^5,*, Jungyeob Ham ^1,2,6,*and Young-Joo Kim ^1,*

¹Institute of Natural Products, Korea Institute of Science and Technology, Gangneung, Republic of Korea.
²Natural Product Applied Science, KIST School, University of Science and Technology, Gangneung, Republic of Korea.
³Department of Pathology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁴Institute of Biological Resources, Chuncheon Bioindustry Foundation, Chuncheon, Republic of Korea.
⁵Department of Biochemistry and Molecular Biology, Brain Korea 21 project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁶NeoCannBio Co. Ltd, Seoul, Republic of Korea.
⁷These authors contributed equally: Youngsic Jeon, Taejung Kim.

^*Corresponding authors: correspondence to Kyung-Chul Choi, Jungyeob Ham or Young-Joo Kim

Abstract

The search for more effective and safer cancer therapies has led to an increasing interest in combination treatments that use well-established agents. Here we explore the potential of cannabidiol (CBD), a compound derived from cannabis, to enhance the anticancer effects of etoposide in non-small cell lung cancer (NSCLC). Although CBD is primarily used to manage childhood epilepsy, its broader therapeutic applications are being actively investigated, particularly in oncology. Our results revealed that, among various tested chemotherapeutic drugs, etoposide showed the most significant reduction in NSCLC cell viability when combined with CBD. To understand this synergistic effect, we conducted extensive transcriptomic and proteomic profiling, which showed that the combination of CBD and etoposide upregulated genes associated with autophagic cell death while downregulating key oncogenes known to drive tumor progression. This dual effect on cell death and oncogene suppression was mediated by inactivation of the PI3K-AKT-mTOR signaling pathway, a crucial regulator of cell growth and survival, and was found to be dependent on the p53 status. Interestingly, our analysis revealed that this combination therapy did not rely on traditional cannabinoid receptors or transient receptor potential cation channels, indicating that CBD exerts its anticancer effects through novel, noncanonical mechanisms. The findings suggest that the combination of CBD with etoposide could represent a groundbreaking approach to NSCLC treatment, particularly in cases where conventional therapies fail. By inducing autophagic cell death and inhibiting oncogenic pathways, this therapeutic strategy offers a promising new avenue for enhancing treatment efficacy in NSCLC, especially in tumors with p53 function.

논문정보

형식Research article
게재일2025년 05월 (BRIC 등록일 2025-05-02)
연구진국내 연구진
분야 의약학 > 분자세포의학

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