Spatial Lipidomics Reveals Anticancer Mechanisms of Bufalin in Combination with Cinobufagin in Tumor-Bearing Mice

Jinghui Zhang, Yanjun HONG, Peisi Xie, Yang Chen, Lilong Jiang, Zhiyi Yang, Guodong Cao, Zhongjian Chen, Xuesong Liu, Yong Chen, Yongjiang Wu*, Zongwei Cai

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Bufalin (BFL) and cinobufagin (CBF) are the principal bioactive constituents of Chansu, a widely used traditional Chinese medicine (TCM). The synergistic effects of potential active components are responsible for the bioactivities of TCM. Our results showed that the cotreatment with BFL and CBF confers superior anticancer efficacy compared to monotreatment. To reveal the underlying mechanisms of their cotreatment, an integrated method composed of mass spectrometry-based lipidomics and matrix-assisted laser desorption/ionization mass spectrometry imaging was used to delineate the responses of tumor-bearing mice treated with BFL and CBF individually or in combination. The cotreatment with BFL and CBF modulated the sphingolipid metabolism and glycerophospholipid metabolism, and subsequently led to mitochondria-driven apoptosis and systemic disruption of biomembranes in tumor cells. Furthermore, we found that the disturbed lipid markers were mainly located in the non-necrotic tumor areas, the essential parts for the formation of solid tumor framework. Together, our findings revealed what occurred in tumor in response to the treatment of BFL and CBF, from lipids to enzymes, and thus provide insights into the critical role of lipid reprogramming in the satisfactory anticancer effect of BFL in combination with CBF.

Original languageEnglish
Article number593815
JournalFrontiers in Pharmacology
Volume11
DOIs
Publication statusPublished - 12 Jan 2021

Scopus Subject Areas

  • Pharmacology
  • Pharmacology (medical)

User-Defined Keywords

  • bufalin
  • chansu
  • cinobufagin
  • lipidomics
  • mass spectrometry imaging

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