XYA-2: a marine-derived compound targeting apoptosis and multiple signaling pathways in pancreatic cancer

Xiaoqing Guan; Yun Li; Xiaodan Guan; Linfei Fan; Jieer Ying

doi:10.7717/peerj.16805

XYA-2: a marine-derived compound targeting apoptosis and multiple signaling pathways in pancreatic cancer

PeerJ. 2024 Jan 16:12:e16805. doi: 10.7717/peerj.16805. eCollection 2024.

Authors

Xiaoqing Guan^#^{1

2}, Yun Li^#¹, Xiaodan Guan¹, Linfei Fan¹, Jieer Ying^{1

2}

Affiliations

¹ Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, China.
² Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Zhejiang, China.

^# Contributed equally.

Abstract

Background: Pancreatic cancer is a highly aggressive and fatal disease with limited treatment options and poor prognosis for patients. This study aimed to investigate the impact of XYA-2 {N-(3,7-dimethyl-2,6-octadienyl)-2-aza-2-deoxychaetoviridin A}, a nitrogenated azaphilon previously reported from a deep-sea-derived fungus on the progression of pancreatic cancer cells.

Methods: The inhibitory effects of XYA-2 on cell proliferation, clonogenic potential, cell cycle progression, apoptosis, migration, and invasion were assessed using various assays. The CCK-8 assay, clone formation assay, flow cytometry assay, wound healing assay, and transwell assay were employed to evaluate cell proliferation, clonogenic potential, cell cycle progression, apoptosis, migration, and invasion, respectively. Moreover, we employed RNA-seq and bioinformatics analyses to uncover the underlying mechanism by which XYA-2 influences pancreatic cancer cells. The revealed mechanism was subsequently validated through qRT-PCR.

Results: Our results demonstrated that XYA-2 dose-dependently inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest and apoptosis. Additionally, XYA-2 exerted a significant inhibitory effect on the invasion and migration of cancer cells. Moreover, XYA-2 was found to regulate the expression of genes involved in multiple cancer-related pathways based on our RNA-seq and bioinformatics analysis.

Conclusion: These findings highlight the potential of XYA-2 as a promising therapeutic option for the treatment of pancreatic cancer.

Keywords: Apoptosis; Cell proliferation; Pancreatic cancer; Pancreatic cancer treatment; XYA-2.

MeSH terms

Apoptosis
Cell Proliferation
Humans
Pancreas
Pancreatic Hormones
Pancreatic Neoplasms* / drug therapy
Signal Transduction

Substances

Pancreatic Hormones

Grants and funding

This research was supported by grants from the Traditional Chinese Medicine Science and Technology Program of Zhejiang Province (2023ZR003), and the Key Laboratory of Prevention, Diagnosis, and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province (2022E10021). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.