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

doi:10.1021/acsmedchemlett.1c00673

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 journal › Article › peer-review

1 Scopus citations

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 language	English (US)
Pages (from-to)	615-622
Number of pages	8
Journal	ACS Medicinal Chemistry Letters
Volume	13
Issue number	4
DOIs	https://doi.org/10.1021/acsmedchemlett.1c00673
State	Published - Apr 14 2022

Keywords

Azapodophyllotoxin
Kidney Cancer
Lymphoma
Monoglycerol
Tubulin

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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title = "Azapodophyllotoxin Causes Lymphoma and Kidney Cancer Regression by Disrupting Tubulin and Monoglycerols",

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.",

keywords = "Azapodophyllotoxin, Kidney Cancer, Lymphoma, Monoglycerol, Tubulin",

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

year = "2022",

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doi = "10.1021/acsmedchemlett.1c00673",

language = "English (US)",

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T1 - Azapodophyllotoxin Causes Lymphoma and Kidney Cancer Regression by Disrupting Tubulin and Monoglycerols

AU - Gouw, Arvin M.

AU - Kumar, Vineet

AU - Resendez, Angel

AU - Alvina, Fidelia B.

AU - Liu, Natalie S.

AU - Margulis, Katherine

AU - Tong, Ling

AU - Zare, Richard N.

AU - Malhotra, Sanjay V.

AU - Felsher, Dean W.

PY - 2022/4/14

Y1 - 2022/4/14

N2 - 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.

AB - 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.

KW - Azapodophyllotoxin

KW - Kidney Cancer

KW - Lymphoma

KW - Monoglycerol

KW - Tubulin

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

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Keywords

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