Azapodophyllotoxin Causes Lymphoma and Kidney Cancer Regression by Disrupting Tubulin and Monoglycerols

Arvin M. Gouw, Vineet Kumar, Angel Resendez, Fidelia B. Alvina, Natalie S. Liu, Katherine Margulis, Ling Tong, Richard N. Zare, Sanjay V. Malhotra, Dean W. Felsher

Research output: Contribution to journalArticlepeer-review

Abstract

A natural compound screen identified several anticancer compounds, among which azapodophyllotoxin (AZP) was found to be the most potent. AZP caused decreased viability of both mouse and human lymphoma and renal cell cancer (RCC) tumor-derived cell lines. Novel AZP derivatives were synthesized and screened identifying compound NSC750212 to inhibit the growth of both lymphoma and RCC both in vitro and in vivo. A nanoimmunoassay was used to assess the NSC750212 mode of action in vivo. On the basis of the structure of AZP and its mode of action, AZP disrupts tubulin polymerization. Through desorption electrospray ionization mass spectrometry imaging, NSC750212 was found to inhibit lipid metabolism. NSC750212 suppresses monoglycerol metabolism depleting lipids and thereby inhibits tumor growth. The dual mode of tubulin polymerization disruption and monoglycerol metabolism inhibition makes NSC750212 a potent small molecule against lymphoma and RCC.

Original languageEnglish (US)
Pages (from-to)615-622
Number of pages8
JournalACS Medicinal Chemistry Letters
Volume13
Issue number4
DOIs
StatePublished - Apr 14 2022
Externally publishedYes

Keywords

  • Azapodophyllotoxin
  • Kidney Cancer
  • Lymphoma
  • Monoglycerol
  • Tubulin

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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