Publication:
P38 inhibitor inhibits the apoptosis of cowanin-treated human colorectal adenocarcinoma cells

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Issued Date

2018

Resource Type

Article

File Type

application/pdf

ISSN

10196439

DOI

10.3892/ijo.2018.4353

Other identifier(s)

2-s2.0-85045395183

Rights Holder(s)

มหาวิทยาลัยศรีนครินทรวิโรฒ

Bibliographic Citation

International Journal of Oncology. Vol 52, No.6 (2018), p.2031-2040

Suggested Citation

Chowchaikong N., Nilwarangkoon S., Laphookhieo S., Tanunyutthawongse C., Watanapokasin R. P38 inhibitor inhibits the apoptosis of cowanin-treated human colorectal adenocarcinoma cells. International Journal of Oncology. Vol 52, No.6 (2018), p.2031-2040. doi:10.3892/ijo.2018.4353 Retrieved from: https://hdl.handle.net/20.500.14740/4291

Title

P38 inhibitor inhibits the apoptosis of cowanin-treated human colorectal adenocarcinoma cells

Author(s)

Chowchaikong N.
 Nilwarangkoon S.
 Laphookhieo S.
 Tanunyutthawongse C.
 Watanapokasin R.

Abstract

Colorectal cancer, which is the third most common type of cancer diagnosed in both men and women, is the leading cause of cancer-related deaths worldwide. Cowanin is a pure compound extracted from Garcinia cowa Roxb., a tree species present in Thailand, Malaysia and Myanmar. The crude extract has been demonstrated to have antitumor activity, inflammation induction, antibacterial activity, anti-inflammatory activity and antimalarial activity. In the present study, the effects of cowanin on apoptosis induction and on the apoptosis- related and mitogen-Activated protein kinase (MAPK) pathways were investigated in the LoVo human colorectal cancer cell line. The cytotoxicity of cowanin in LoVo cells was determined by MTT assay. Hoechst 33342 and JC-1 staining were used to determine nuclear morphological changes and mitochondrial membrane potential, respectively. The expression levels of BCL2 apoptosis regulator (Bcl-2) family, MAPK and AKT serine/threonine kinase 1 (Akt) pathway proteins following cowanin treatment were determined by western blot analysis. The results demonstrated that cowanin inhibited cell proliferation and induced cell death via the apoptosis pathway. Cowanin treatment increased BCL2 associated X (Bax) and decreased Bcl-2 expression. In addition, cowanin activated caspase-9, -7 and poly-ADP-ribose-polymerase expression. Furthermore, cowanin decreased the levels of phosphorylated extracellular signal-regulated kinase (p-ERK), p-Akt, p-3-phosphoinositide-dependent protein kinase-1, while it increased p-p38 expression, thus resulting in the induction of apoptosis. In conclusion, cowanin inhibited cell proliferation and induced apoptosis of LoVo cells via the MAPK and Akt signaling pathways. Notably, inhibition of p38 by using a p38 inhibitor (SB203580) prevented the cowanin-induced apoptosis in LoVo cells. These results suggested that cowanin may be a potential candidate for the treatment of colorectal cancer and provided important information on the molecular mechanisms underlying its antitumor activity. © 2018 Spandidos Publications. All rights reserved.

Subject(s)

Antineoplastic agent
 Caspase 7
 Caspase 9
 Cowanin
 Hoe 33342
 Mitogen activated protein kinase
 Mitogen activated protein kinase p38 inhibitor
 Nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase
 Phosphoinositide dependent protein kinase 1
 Protein Bax
 Protein bcl 2
 Protein kinase B
 Unclassified drug
 Xanthone derivative
 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole
 CASP7 protein, human
 CASP9 protein, human
 Caspase 7
 Caspase 9
 Cowaniin
 Imidazole derivative
 Mitogen activated protein kinase p38
 Nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase
 Protein kinase B
 Pyridine derivative
 Tannin derivative
 Akt signaling
 Antiproliferative activity
 Apoptosis
 Article
 Cell death
 Cell nucleus
 Cell structure
 Cell survival
 Cell viability
 Controlled study
 Drug cytotoxicity
 Drug mechanism
 Drug structure
 Human
 Human cell
 LoVo cell line
 Mitochondrial membrane potential
 MTT assay
 Priority journal
 Protein expression level
 Protein synthesis
 Western blotting
 Antagonists and inhibitors
 Cell cycle
 Cell proliferation
 Chemistry
 Colorectal tumor
 Drug effect
 Gene expression regulation
 MAPK signaling
 Metabolism
 Tumor cell line
 Caspase 7
 Caspase 9
 Cell Cycle
 Cell Line, Tumor
 Cell Proliferation
 Cell Survival
 Colorectal Neoplasms
 Gene Expression Regulation, Neoplastic
 Humans
 Imidazoles
 MAP Kinase Signaling System
 P38 Mitogen-Activated Protein Kinases
 Poly(ADP-ribose) Polymerases
 Proto-Oncogene Proteins c-akt
 Pyridines
 Tannins

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URI

https://hdl.handle.net/20.500.14740/4291

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Scopus: Year 1983-2021

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