Abstract | PURPOSE: METHODS: RESULTS:
Thiaminase I enzyme was cytotoxic in six breast cancer cell lines with IC(50)s ranging from 0.012 to 0.022 U/ml. The growth inhibitory effects of the combination of thiaminase I with either doxorubicin or paclitaxel were also examined. Over a wide range of drug concentrations, thiaminase 1 was consistently synergistic or additive with doxorubicin and paclitaxel in MCF-7, ZR75, HS578T and T47D cell lines, with most combinations having a calculated combination index (CI) of less than 0.8, indicating synergy. Although thiaminase I exposure did not stimulate the energy-sensing signaling kinases AKT, AMPK and GSK-3beta in MCF-7, ZR75, HS578T and T47D cell lines, thiaminase I exposure did stimulate expression of the ER stress response protein GRP78. In summary, thiaminase I is cytotoxic in breast cancer cell lines and triggers the unfolded protein response. CONCLUSION:
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Authors | Shuqian Liu, Noel R Monks, Jeremiah W Hanes, Tadhg P Begley, Hui Yu, Jeffrey A Moscow |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 66
Issue 1
Pg. 171-9
(May 2010)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 19830429
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Endoplasmic Reticulum Chaperone BiP
- HSPA5 protein, human
- Heat-Shock Proteins
- Hspa5 protein, mouse
- Membrane Transport Proteins
- Recombinant Proteins
- SLC19A3 protein, human
- Doxorubicin
- Adenosine Triphosphate
- Alkyl and Aryl Transferases
- thiamin pyridinylase
- GSK3B protein, human
- Glycogen Synthase Kinase 3 beta
- Gsk3b protein, mouse
- Proto-Oncogene Proteins c-akt
- Glycogen Synthase Kinase 3
- AMP-Activated Protein Kinases
- Paclitaxel
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Topics |
- AMP-Activated Protein Kinases
(metabolism)
- Adenosine Triphosphate
(metabolism)
- Alkyl and Aryl Transferases
(administration & dosage, therapeutic use)
- Animals
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Doxorubicin
(administration & dosage, therapeutic use)
- Drug Screening Assays, Antitumor
- Drug Synergism
- Endoplasmic Reticulum Chaperone BiP
- Female
- Glycogen Synthase Kinase 3
(metabolism)
- Glycogen Synthase Kinase 3 beta
- Heat-Shock Proteins
(metabolism)
- Humans
- Membrane Transport Proteins
(metabolism)
- Mice
- Mice, Nude
- Paclitaxel
(administration & dosage, therapeutic use)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Recombinant Proteins
(isolation & purification, therapeutic use)
- Thiamine Deficiency
(metabolism)
- Unfolded Protein Response
(drug effects)
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