Zeylenone-mediated inhibition of TIMP-1-induced Bax/Bcl-2/Cle-caspase-3 expression and apoptosis via FAK-PI3K/AKT pathway regulation in thyroid cancer cells: in vitro and in silico study.

Authors

Shichen Qin, Jie Zhou, Xuemei Wu, Liangxing Jiang

Published in

3 Biotech. Volume 16. Issue 8. Pages 304. Epub Jul 04, 2026.

Abstract

Thyroid cancer, a prevalent endocrine malignancy, has shown a significant global rise in incidence over the past 15 years and currently ranks as the sixth most common cancer worldwide, with higher prevalence among women. Dysregulation of the TIMP-1-induced FAK/PI3K/AKT signaling pathway plays a pivotal role in disease progression, highlighting its potential as a therapeutic target. This study investigated the anticancer effects of zeylenone in thyroid carcinogenesis, based on its reported inhibition of TIMP-1-mediated FAK/PI3K/AKT signaling in tumor cells. The ability of zeylenone to suppress proliferation of TPC-1 thyroid cancer cells and the underlying molecular mechanisms were evaluated through analyses of cell viability, oxidative stress, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), apoptosis, and cell proliferation, with an emphasis on the TIMP-1/FAK/PI3K/AKT pathway. Zeylenone significantly suppressed cell proliferation, induced apoptosis, increased ROS and TBARS levels, reduced MMP, decreased antioxidant status, and inhibited TIMP-1-induced FAK/PI3K/AKT signaling. In silico docking analyses demonstrated interactions between zeylenone and key apoptotic and cell-cycle regulators, including Bax, Cyclin E1, and CDK2, while molecular dynamics simulations using Schrödinger's Desmond module confirmed the stability of the zeylenone-CDK2 complex. However, limitations include the use of a single cell line (TPC-1) and a lack of in vivo validation. Future perspectives involve testing in additional thyroid cancer models, animal studies, and clinical translation to assess efficacy and safety. Collectively, these findings demonstrate that zeylenone suppresses proliferation and promotes apoptosis in TPC-1 cells primarily through suppression of the TIMP-1-mediated FAK/PI3K/AKT signaling pathway, highlighting its potential as a therapeutic candidate for thyroid carcinoma.

PMID:
42404973
Bibliographic data and abstract were imported from PubMed on 06 Jul 2026.

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