Network pharmacology-based prediction and experimental verification of the involvement of the PI3K/Akt pathway in the anti-thyroid cancer activity of crocin.

Yan Tang, Han Yang, Jinsong Yu, Zhong Li, Quanxiao Xu, Qiu Xu, Guangwei Jia, Na Sun

Journal: Archives of biochemistry and biophysics 2023;743():109643

PMID: 37211223

Full Text on Elsevier Science View on PubMed

Abstract

Crocin, a unique water-soluble carotenoid extracted from saffron, is known to exert anticancer activity against various cancer types, including thyroid cancer (TC). However, the detailed mechanism underlying the anticancer effect of crocin in TC needs further exploration. Targets of crocin and targets associated with TC were acquired from public databases. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using DAVID. Cell viability and proliferation were assessed using MMT and EdU incorporation assays, respectively. Apoptosis was assessed using TUNEL and caspase-3 activity assays. The effect of crocin on phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) was explored by western blot analysis. A total of 20 overlapping targets were identified as candidate targets of crocin against TC. GO analysis showed that these overlapping genes were significantly enriched in the positive regulation of cell proliferation. KEGG results showed that the PI3K/Akt pathway was involved in the effect of crocin against TC. Crocin treatment inhibited cell proliferation and promoted apoptosis in TC cells. Moreover, we found that crocin inhibited the PI3K/Akt pathway in TC cells. 740Y-P treatment reversed the effects of crocin on TC cells. In conclusion, crocin suppressed proliferation and elicited apoptosis in TC cells via inactivation of the PI3K/Akt pathway.

Address: Department of General Surgery, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, Henan, 473004, China.; Department of Endocrinology, Nanshi Hospital Affiliated to Henan University, Nanyang, Henan, 473065, China.; Department of Thyroid and Breast Surgery, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, Henan, 473004, China; Key Laboratory of Thyroid Tumor Prevention and Treatment of Nanyang, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, Henan, 473004, China. Electronic address: [email protected].; Department of Oncology, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, Henan, 473004, China.; Department of Thyroid and Breast Surgery, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, Henan, 473004, China; Key Laboratory of Thyroid Tumor Prevention and Treatment of Nanyang, Nanyang First People's Hospital Affiliated to Henan University, Nanyang, Henan, 473004, China.; Department of Invasive Technology, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, 223302, China.

DOI: 10.1016/j.abb.2023.109643

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MeSH Terms: Humans, Proto-Oncogene Proteins c-akt, Phosphatidylinositol 3-Kinase, Phosphatidylinositol 3-Kinases, Signal Transduction, Network Pharmacology, Carotenoids, Thyroid Neoplasms, Apoptosis