A novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy

Tsung I. Hsu; Ying Jung Chen; Chia Yang Hung; Yi Chang Wang; Sin Jin Lin; Wu Chou Su; Ming Derg Lai; Sang Yong Kim; Qiang Wang; Keduo Qian; Masuo Goto; Yu Zhao; Yoshiki Kashiwada; Kuo Hsiung Lee; Wen Chang Chang; Jan Jong Hung

doi:10.18632/oncotarget.3701

A novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy

Tsung I. Hsu, Ying Jung Chen, Chia Yang Hung, Yi Chang Wang, Sin Jin Lin, Wu Chou Su, Ming Derg Lai, Sang Yong Kim, Qiang Wang, Keduo Qian, Masuo Goto, Yu Zhao, Yoshiki Kashiwada, Kuo Hsiung Lee, Wen Chang Chang, Jan Jong Hung

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

Herein, we evaluated the anti-cancer effect and molecular mechanisms of a novel betulinic acid (BA) derivative, SYK023, by using two mouse models of lung cancer driven by Kras^G12D or EGFR^L858R. We found that SYK023 inhibits lung tumor proliferation, without side effects in vivo or cytotoxicity in primary lung cells in vitro. SYK023 triggered endoplasmic reticulum (ER) stress. Blockage of ER stress in SYK023-treated cells inhibited SYK023-induced apoptosis. In addition, we found that the expression of cell cycle-related genes, including cyclin A2, B1, D3, CDC25a, and CDC25b decreased but, while those of p15^INK4b, p16^INK4a, and p21^CIP1 increased following SYK023 treatment. Finally, low doses of SYK023 significantly decreased lung cancer metastasis in vitro and in vivo. Expression of several genes related to cell migration, including synaptopodin, were downregulated by SYK023, thereby impairing F-actin polymerization and metastasis. Therefore, SYK023 may be a potentially therapeutic treatment for metastatic lung cancer.

Original language	English
Pages (from-to)	13671-13687
Number of pages	17
Journal	Oncotarget
Volume	6
Issue number	15
DOIs	https://doi.org/10.18632/oncotarget.3701
Publication status	Published - 2015

Keywords

ER stress
Metastasis
Synaptopodin
syk023

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.3701

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title = "A novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy",

abstract = "Herein, we evaluated the anti-cancer effect and molecular mechanisms of a novel betulinic acid (BA) derivative, SYK023, by using two mouse models of lung cancer driven by KrasG12D or EGFRL858R. We found that SYK023 inhibits lung tumor proliferation, without side effects in vivo or cytotoxicity in primary lung cells in vitro. SYK023 triggered endoplasmic reticulum (ER) stress. Blockage of ER stress in SYK023-treated cells inhibited SYK023-induced apoptosis. In addition, we found that the expression of cell cycle-related genes, including cyclin A2, B1, D3, CDC25a, and CDC25b decreased but, while those of p15INK4b, p16INK4a, and p21CIP1 increased following SYK023 treatment. Finally, low doses of SYK023 significantly decreased lung cancer metastasis in vitro and in vivo. Expression of several genes related to cell migration, including synaptopodin, were downregulated by SYK023, thereby impairing F-actin polymerization and metastasis. Therefore, SYK023 may be a potentially therapeutic treatment for metastatic lung cancer.",

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author = "Hsu, {Tsung I.} and Chen, {Ying Jung} and Hung, {Chia Yang} and Wang, {Yi Chang} and Lin, {Sin Jin} and Su, {Wu Chou} and Lai, {Ming Derg} and Kim, {Sang Yong} and Qiang Wang and Keduo Qian and Masuo Goto and Yu Zhao and Yoshiki Kashiwada and Lee, {Kuo Hsiung} and Chang, {Wen Chang} and Hung, {Jan Jong}",

year = "2015",

doi = "10.18632/oncotarget.3701",

language = "English",

volume = "6",

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T1 - A novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy

AU - Hsu, Tsung I.

AU - Chen, Ying Jung

AU - Hung, Chia Yang

AU - Wang, Yi Chang

AU - Lin, Sin Jin

AU - Su, Wu Chou

AU - Lai, Ming Derg

AU - Kim, Sang Yong

AU - Wang, Qiang

AU - Qian, Keduo

AU - Goto, Masuo

AU - Zhao, Yu

AU - Kashiwada, Yoshiki

AU - Lee, Kuo Hsiung

AU - Chang, Wen Chang

AU - Hung, Jan Jong

PY - 2015

Y1 - 2015

N2 - Herein, we evaluated the anti-cancer effect and molecular mechanisms of a novel betulinic acid (BA) derivative, SYK023, by using two mouse models of lung cancer driven by KrasG12D or EGFRL858R. We found that SYK023 inhibits lung tumor proliferation, without side effects in vivo or cytotoxicity in primary lung cells in vitro. SYK023 triggered endoplasmic reticulum (ER) stress. Blockage of ER stress in SYK023-treated cells inhibited SYK023-induced apoptosis. In addition, we found that the expression of cell cycle-related genes, including cyclin A2, B1, D3, CDC25a, and CDC25b decreased but, while those of p15INK4b, p16INK4a, and p21CIP1 increased following SYK023 treatment. Finally, low doses of SYK023 significantly decreased lung cancer metastasis in vitro and in vivo. Expression of several genes related to cell migration, including synaptopodin, were downregulated by SYK023, thereby impairing F-actin polymerization and metastasis. Therefore, SYK023 may be a potentially therapeutic treatment for metastatic lung cancer.

AB - Herein, we evaluated the anti-cancer effect and molecular mechanisms of a novel betulinic acid (BA) derivative, SYK023, by using two mouse models of lung cancer driven by KrasG12D or EGFRL858R. We found that SYK023 inhibits lung tumor proliferation, without side effects in vivo or cytotoxicity in primary lung cells in vitro. SYK023 triggered endoplasmic reticulum (ER) stress. Blockage of ER stress in SYK023-treated cells inhibited SYK023-induced apoptosis. In addition, we found that the expression of cell cycle-related genes, including cyclin A2, B1, D3, CDC25a, and CDC25b decreased but, while those of p15INK4b, p16INK4a, and p21CIP1 increased following SYK023 treatment. Finally, low doses of SYK023 significantly decreased lung cancer metastasis in vitro and in vivo. Expression of several genes related to cell migration, including synaptopodin, were downregulated by SYK023, thereby impairing F-actin polymerization and metastasis. Therefore, SYK023 may be a potentially therapeutic treatment for metastatic lung cancer.

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A novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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