Trilobolide-6-O-isobutyrate exerts anti-tumor effects on cholangiocarcinoma cells through inhibiting JAK/STAT3 signaling pathway

Hao-Xuan Zhang; Rui Fan; Qian-En Chen; Lin-Jun Zhang; Yang Hui; Peng Xu; Si-Yang Li; Guang-Ying Chen; Wen-Hao Chen; Dong-Yan Shen

doi:10.1016/j.heliyon.2024.e27217

Trilobolide-6-O-isobutyrate exerts anti-tumor effects on cholangiocarcinoma cells through inhibiting JAK/STAT3 signaling pathway

Heliyon. 2024 Feb 28;10(5):e27217. doi: 10.1016/j.heliyon.2024.e27217. eCollection 2024 Mar 15.

Authors

Affiliations

¹ School of Medicine, Xiamen University, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China.
² Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, Hainan Normal University, Haikou, 570100, China.

Abstract

Trilobolide-6-O-isobutyrate exhibits significant antitumor effects on cholangiocarcinoma (CCA) cells by effectively inhibiting the JAK/STAT3 signaling pathway. This study aims to investigate the mechanisms underlying the antitumor properties of trilobolide-6-O-isobutyrate, and to explore its potential as a therapeutic agent for CCA. This study illustrates that trilobolide-6-O-isobutyrate efficiently suppresses CCA cell proliferation in a dose- and time-dependent manner. Furthermore, trilobolide-6-O-isobutyrate stimulates the production of reactive oxygen species, leading to oxidative stress and initiation of apoptosis via the activation of the mitochondrial pathway. Data from xenograft tumor assays in nude mice confirms that TBB inhibits tumor growth, and that there are no obvious toxic effects or side effects in vivo. Mechanistically, trilobolide-6-O-isobutyrate exerts antitumor effects by inhibiting STAT3 transcriptional activation, reducing PCNA and Bcl-2 expression, and increasing P21 expression. These findings emphasizes the potential of trilobolide-6-O-isobutyrate as a promising therapeutic candidate for the treatment of CCA.

Keywords: Apoptosis; Cholangiocarcinoma; JAK/STAT pathway; Proliferation; TBB.