Traditional Herbal Formula Taeeumjowi-Tang (TJ001) Inhibits p53-Mutant Prostate Cancer Cells Growth by Activating AMPK-Dependent Pathway
Joint Authors
Ko, Seong-Gyu
Kim, Ji Hye
Kang, Sooyeon
Kim, Hyo In
Choi, Yu-Jeong
Lee, Seul Ki
Cheon, Chunhoo
Source
Evidence-Based Complementary and Alternative Medicine
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-05-05
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Dysregulated lipid metabolism is a prominent feature of prostate cancers (PCas); several enzymes involved in lipid accumulation are highly expressed.
Here, we elucidated efficacy of TJ001, a traditional herbal decoction, in inhibiting de novo lipogenesis.
TJ001 had significant cytotoxicity against DU145 but not PC3 and LNCaP cells and, similarly, TJ001 markedly AMPK phosphorylation only in DU145 cells.
This was accompanied by the downregulation of phosphorylated-acetyl coenzyme A carboxylase (ACC) expression and sterol regulatory element-binding protein 1 (SREBP1) proteolytic cleavage, thereby inhibiting its role as a transcription factor to induce lipid biosynthesis.
When Oil Red O staining was performed, it is reflected in the reduction of lipid droplets (LDs).
TJ001 also induced G1/S cell cycle arrest via a cell cycle inhibitor (CKI) p21WAF1/CIP1 upregulation.
Although p53 proteins remained unchanged, both cyclin E and cyclin D1 were decreased.
Moreover, TJ001 suppressed the mammalian target of rapamycin (mTOR) signaling pathway.
Generally, the prolonged G1/S phase arrest accompanies apoptosis, but TJ001 failed to work as a trigger apoptosis in DU145 cells.
We showed that mutant p53 proteins were required for the survival of DU145 cells.
In presence of TJ001, inhibition of endogenous mutant p53 by RNAi led to cell viability reduction and induction of the p-AMPK/AMPK ratio.
In addition, it induced apoptotic cell death in DU145 cells.
At the cellular level, induction of PARP, caspase-3, and caspase-9 cleavages was observed, and caspase-3 activity was increased in the p53 knockdown cells treated with TJ001.
Taken together, we demonstrated that TJ001 inhibited cell growth in DU145 prostate cancer cells as indicated by blocking lipogenesis and induction in G1/S cell cycle arrest.
In addition, we may provide an evidence that mutant p53 protein has potential role as an oncogenic action in DU145 cells.
Collectively, the combination of mutant p53 targeting and TJ001 treatment resulted in decreased cell growth in DU145 cells.
American Psychological Association (APA)
Kang, Sooyeon& Kim, Hyo In& Choi, Yu-Jeong& Lee, Seul Ki& Kim, Ji Hye& Cheon, Chunhoo…[et al.]. 2019. Traditional Herbal Formula Taeeumjowi-Tang (TJ001) Inhibits p53-Mutant Prostate Cancer Cells Growth by Activating AMPK-Dependent Pathway. Evidence-Based Complementary and Alternative Medicine،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1148956
Modern Language Association (MLA)
Kang, Sooyeon…[et al.]. Traditional Herbal Formula Taeeumjowi-Tang (TJ001) Inhibits p53-Mutant Prostate Cancer Cells Growth by Activating AMPK-Dependent Pathway. Evidence-Based Complementary and Alternative Medicine No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1148956
American Medical Association (AMA)
Kang, Sooyeon& Kim, Hyo In& Choi, Yu-Jeong& Lee, Seul Ki& Kim, Ji Hye& Cheon, Chunhoo…[et al.]. Traditional Herbal Formula Taeeumjowi-Tang (TJ001) Inhibits p53-Mutant Prostate Cancer Cells Growth by Activating AMPK-Dependent Pathway. Evidence-Based Complementary and Alternative Medicine. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1148956
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1148956