Publication:
Apoptosis induction associated with the ER stress response through up-regulation of JNK in HeLa cells by gambogic acid

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Issued Date

2015

Resource Type

Article

File Type

application/pdf

ISSN

14726882

DOI

10.1186/s12906-015-0544-4

Other identifier(s)

2-s2.0-84924338427

Rights Holder(s)

Scopus

Bibliographic Citation

BMC Complementary and Alternative Medicine. Vol 15, No.1 (2015)

Suggested Citation

Krajarng A., Imoto M., Tashiro E., Fujimaki T., Shinjo S., Watanapokasin R. Apoptosis induction associated with the ER stress response through up-regulation of JNK in HeLa cells by gambogic acid. BMC Complementary and Alternative Medicine. Vol 15, No.1 (2015). doi:10.1186/s12906-015-0544-4 Retrieved from: https://hdl.handle.net/20.500.14740/6171

Title

Apoptosis induction associated with the ER stress response through up-regulation of JNK in HeLa cells by gambogic acid

Author(s)

Krajarng A.
 Imoto M.
 Tashiro E.
 Fujimaki T.
 Shinjo S.
 Watanapokasin R.

Abstract

Background: Gambogic acid (GA) was extracted from the dried yellow resin of gamboge (Garcinia hanburyi) which is traditionally used as a coloring material for painting and cloth dying. Gamboge has been also used as a folk medicine for an internal purgative and externally infected wound. We focused on the mechanisms of apoptosis induction by GA through the unfold protein response (ER stress) in HeLa cells. Methods: The cytotoxic effect of GA against HeLa cells was determined by trypan blue exclusion assay. Markers of ER stress such as XBP-1, GRP78, CHOP, GADD34 and ERdj4 were analyzed by RT-PCR and Real-time RT-PCR. Cell morphological changes and apoptotic proteins were performed by Hoechst33342 staining and Western blotting technique. Results: Our results indicated a time- and dose-dependent decrease of cell viability by GA. The ER stress induction is determined by the up-regulation of spliced XBP1 mRNA and activated GRP78, CHOP, GADD34 and ERdj4 expression. GA also induced cell morphological changes such as nuclear condensation, membrane blebbing and apoptotic body in Hela cells. Apoptosis cell death detected by increased DR5, caspase-8, -9, and -3 expression as well as increased cleaved-PARP, while decreased Bcl-2 upon GA treatment. In addition, phosphorylated JNK was up-regulated but phosphorylated ERK was down-regulated after exposure to GA. Conclusions: These results suggest that GA induce apoptosis associated with the ER stress response through up-regulation of p-JNK and down-regulation of p-ERK in HeLa cells. © 2015 Krajarng et al.

Subject(s)

BIM protein
 Caspase 3
 Caspase 8
 Caspase 9
 Death receptor 5
 Endoplasmic reticulum localized DnaJ homologue protein
 Gambogic acid
 Glucose regulated protein 78
 Growth arrest and DNA damage inducible protein 153
 Growth arrest and DNA damage inducible protein 34
 Hoe 33342
 Nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase
 Nucleic acid binding protein
 Procaspase 3
 Procaspase 8
 Procaspase 9
 Protein bcl 2
 Protein DnaJ
 Stress activated protein kinase
 Tunicamycin
 Unclassified drug
 X box binding protein 1
 Antineoplastic agent
 Gambogic acid
 Heat shock protein
 Mitogen activated protein kinase
 Molecular chaperone GRP78
 Plant extract
 Stress activated protein kinase
 Xanthone derivative
 Antineoplastic activity
 Apoptosis
 Article
 Binding site
 Bright field microscopy
 Cancer cell culture
 Cancer inhibition
 Cell proliferation
 Cell structure
 Cell survival
 Cell viability
 Concentration response
 Controlled study
 DNA flanking region
 Down regulation
 Endoplasmic reticulum stress
 Enzyme phosphorylation
 Female
 Fluorescence microscopy
 Garcinia
 Garcinia hanburyi
 HeLa cell line
 Human
 Human cell
 Protein cleavage
 Protein expression
 Protein localization
 Real time polymerase chain reaction
 Reverse transcription polymerase chain reaction
 Upregulation
 Uterine cervix cancer
 Western blotting
 Apoptosis
 Chemistry
 Drug effects
 Metabolism
 Phytotherapy
 Transcription initiation
 Upregulation
 Uterine Cervical Neoplasms
 Antineoplastic Agents, Phytogenic
 Apoptosis
 Cell Survival
 Down-Regulation
 Endoplasmic Reticulum Stress
 Extracellular Signal-Regulated MAP Kinases
 Female
 Garcinia
 Heat-Shock Proteins
 HeLa Cells
 Humans
 JNK Mitogen-Activated Protein Kinases
 Phytotherapy
 Plant Extracts
 Transcriptional Activation
 Up-Regulation
 Uterine Cervical Neoplasms
 Xanthones

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URI

https://hdl.handle.net/20.500.14740/6171

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Scopus: Year 1983-2021

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