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A novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy.
- Source :
-
Oncotarget [Oncotarget] 2015 May 30; Vol. 6 (15), pp. 13671-87. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Cell Line, Tumor
Cell Movement drug effects
Cell Proliferation drug effects
Disease Models, Animal
Humans
Lung Neoplasms pathology
Male
Mice
Mice, Inbred BALB C
Mice, SCID
Mice, Transgenic
Neoplasm Metastasis
Pentacyclic Triterpenes
Prognosis
Transfection
Xenograft Model Antitumor Assays
Betulinic Acid
Antineoplastic Agents pharmacology
Lung Neoplasms drug therapy
Triterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 25909174
- Full Text :
- https://doi.org/10.18632/oncotarget.3701