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Differential induction of apaptosis in human breast cancer cell lines by phenethyl isothiocyanate, a glutathione depleting agent

Differential induction of apaptosis in human breast cancer cell lines by phenethyl isothiocyanate, a glutathione depleting agent
Differential induction of apaptosis in human breast cancer cell lines by phenethyl isothiocyanate, a glutathione depleting agent
Phenethyl isothiocyanate (PEITC) is a naturally occurring electrophile which depletes intracellular glutathione (GSH) levels and triggers accumulation of reactive oxygen species (ROS). PEITC is of considerable interest as a potential chemopreventive/chemotherapeutic agent, and in this work, we have investigated the effects of PEITC on human breast cancer cell lines. Whereas PEITC readily induced apoptosis in MDA-MB-231 cells (associated with rapid activation of caspases 9 and 3, and decreased expression of BAX), MCF7 cells were relatively resistant to the apoptosis promoting effects of PEITC. The relative resistance of MCF7 cells was associated with high basal expression of NRF2, a transcription factor that coordinates cellular protective responses to oxidants and electrophiles and raised intracellular levels of GSH. This raised basal expression of NRF2 appeared to be a response to on-going production of ROS, since treatment with the antioxidant and GSH precursor N-acetylcysteine (NAC) reduced NRF2 expression. Moreover, pre-treatment of MDA-MB-231 cells with NAC rendered these cells relatively resistant to PEITC-induced apoptosis. In summary, our data confirm that PEITC may be an effective chemopreventive/therapeutic agents for breast cancer. However, differences in the basal expression of NRF2 and resultant changes in GSH levels may be an important determinant of sensitivity to PEITC-induced apoptosis.
1355-8145
529-538
Syed Alwi, Sharifah S.
58980b19-b871-4df6-858b-7aa192f094e5
Cavell, Breeze E.
e85ef588-d947-44c3-904f-32f7b61bd610
Donlevy, Alison
c088848d-cbdc-4c82-9c7f-56bc4bde2317
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Syed Alwi, Sharifah S.
58980b19-b871-4df6-858b-7aa192f094e5
Cavell, Breeze E.
e85ef588-d947-44c3-904f-32f7b61bd610
Donlevy, Alison
c088848d-cbdc-4c82-9c7f-56bc4bde2317
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394

Syed Alwi, Sharifah S., Cavell, Breeze E., Donlevy, Alison and Packham, Graham (2012) Differential induction of apaptosis in human breast cancer cell lines by phenethyl isothiocyanate, a glutathione depleting agent. Cell Stress and Chaperones, 17 (5), 529-538. (doi:10.1007/s12192-012-0329-3). (PMID:22351438)

Record type: Article

Abstract

Phenethyl isothiocyanate (PEITC) is a naturally occurring electrophile which depletes intracellular glutathione (GSH) levels and triggers accumulation of reactive oxygen species (ROS). PEITC is of considerable interest as a potential chemopreventive/chemotherapeutic agent, and in this work, we have investigated the effects of PEITC on human breast cancer cell lines. Whereas PEITC readily induced apoptosis in MDA-MB-231 cells (associated with rapid activation of caspases 9 and 3, and decreased expression of BAX), MCF7 cells were relatively resistant to the apoptosis promoting effects of PEITC. The relative resistance of MCF7 cells was associated with high basal expression of NRF2, a transcription factor that coordinates cellular protective responses to oxidants and electrophiles and raised intracellular levels of GSH. This raised basal expression of NRF2 appeared to be a response to on-going production of ROS, since treatment with the antioxidant and GSH precursor N-acetylcysteine (NAC) reduced NRF2 expression. Moreover, pre-treatment of MDA-MB-231 cells with NAC rendered these cells relatively resistant to PEITC-induced apoptosis. In summary, our data confirm that PEITC may be an effective chemopreventive/therapeutic agents for breast cancer. However, differences in the basal expression of NRF2 and resultant changes in GSH levels may be an important determinant of sensitivity to PEITC-induced apoptosis.

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Accepted/In Press date: 3 February 2012
e-pub ahead of print date: 17 February 2012
Published date: September 2012
Organisations: Cancer Sciences

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Local EPrints ID: 394519
URI: https://eprints.soton.ac.uk/id/eprint/394519
ISSN: 1355-8145
PURE UUID: 148c4a73-56cb-44a4-9635-66df7da5d51f
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 20 May 2016 08:37
Last modified: 20 Jul 2019 01:08

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Contributors

Author: Sharifah S. Syed Alwi
Author: Breeze E. Cavell
Author: Alison Donlevy
Author: Graham Packham ORCID iD

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