Celastrol in cancer therapy: Recent developments, challenges and prospects

Hannah Ying Lim; Pei Shi Ong; Lingzhi Wang; Arul Goel; Lingwen Ding; Andrea Li-Ann Wong; Paul Chi-Lui Ho; Gautam Sethi; Xiaoqiang Xiang; Boon Cher Goh

doi:10.1016/j.canlet.2021.08.030

Celastrol in cancer therapy: Recent developments, challenges and prospects

Cancer Lett. 2021 Sep 8:521:252-267. doi: 10.1016/j.canlet.2021.08.030. Online ahead of print.

Authors

Affiliations

¹ Department of Pharmacy, National University of Singapore, 117559, Singapore; Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore.
² Department of Pharmacy, National University of Singapore, 117559, Singapore.
³ Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore.
⁴ La Canada High School, La Canada Flintridge, CA, 91011, USA.
⁵ Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁶ Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Haematology-Oncology, National University Cancer Institute, 119228, Singapore.
⁷ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore. Electronic address: phcgs@nus.edu.sg.
⁸ Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai, 201203, PR China. Electronic address: xiangxq@fudan.edu.cn.
⁹ Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore; Department of Haematology-Oncology, National University Cancer Institute, 119228, Singapore. Electronic address: phcgbc@nus.edu.sg.

PMID: 34508794
DOI: 10.1016/j.canlet.2021.08.030

Abstract

Cancer is one of the world's biggest healthcare burdens and despite the current advancements made in treatment plans, the outcomes for oncology patients have yet to reach their full potential. Hence, there is a pressing need to develop novel anti-cancer drugs. A popular drug class for research are natural compounds, due to their multi-targeting potential and enhanced safety profile. One such promising natural bioactive compound derived from a vine, Tripterygium wilfordii is celastrol. Pre-clinical studies revolving around the use of celastrol have revealed positive pharmacological activities in various types of cancers, thus suggesting the chemical's potential anti-cancerous effects. However, despite the numerous preclinical studies carried out over the past few decades, celastrol has not reached human trials for cancer. In this review, we summarize the mechanisms and therapeutic potentials of celastrol in treatment for different types of cancer. Subsequently, we also explore the possible reasons hindering its development for human use as cancer therapy, like its narrow therapeutic window and poor pharmacokinetic properties. Additionally, after critically analysing both in vitro and in vivo evidence, we discuss about the key pathways effected by celastrol and the suitable types of cancer that can be targeted by the natural drug, thus giving insight into future directions that can be taken, such as in-depth analysis and research of the druggability of celastrol derivatives, to aid the clinical translation of this promising anti-cancer lead compound.

Keywords: Anti-cancer activity; Celastrol; Pharmacokinetics; Toxicity; Translational potential.