δ-Tocotrienol Oxazine Derivative Antagonizes Mammary Tumor Cell Compensatory Response to CoCl2-Induced Hypoxia
Joint Authors
Behery, Fathy A.
Sylvester, Paul W.
Nazzal, Sami
El Sayed, Khalid
Parajuli, Parash
Alayoubi, Alaadin Y.
Ananthula, Suryatheja
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-07-22
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
In response to low oxygen supply, cancer cells elevate production of HIF-1α, a hypoxia-inducible transcription factor that subsequently acts to stimulate blood vessel formation and promote survival.
Studies were conducted to determine the role of δ-tocotrienol and a semisynthetic δ-tocotrienol oxazine derivative, compound 44, on +SA mammary tumor cell hypoxic response.
Treatment with 150 µM CoCl2 induced a hypoxic response in +SA mammary tumor cells as evidenced by a large increase in HIF-1α levels, and combined treatment with compound 44 attenuated this response.
CoCl2-induced hypoxia was also associated with a large increase in Akt/mTOR signaling, activation of downstream targets p70S6K and eIF-4E1, and a significant increase in VEGF production, and combined treatment with compound 44 blocked this response.
Additional in vivo studies showed that intralesional treatment with compound 44 in BALB/c mice bearing +SA mammary tumors significantly decreased the levels of HIF-1α, and this effect was associated with a corresponding decrease in Akt/mTOR signaling and activation of downstream targets p70S6kinase and eIF-4E1.
These findings demonstrate that treatment with the δ-tocotrienol oxazine derivative, compound 44, significantly attenuates +SA mammary tumor cell compensatory responses to hypoxia and suggests that this compound may provide benefit in the treatment of rapidly growing solid breast tumors.
American Psychological Association (APA)
Ananthula, Suryatheja& Parajuli, Parash& Behery, Fathy A.& Alayoubi, Alaadin Y.& Nazzal, Sami& El Sayed, Khalid…[et al.]. 2014. δ-Tocotrienol Oxazine Derivative Antagonizes Mammary Tumor Cell Compensatory Response to CoCl2-Induced Hypoxia. BioMed Research International،Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-460399
Modern Language Association (MLA)
Ananthula, Suryatheja…[et al.]. δ-Tocotrienol Oxazine Derivative Antagonizes Mammary Tumor Cell Compensatory Response to CoCl2-Induced Hypoxia. BioMed Research International No. 2014 (2014), pp.1-13.
https://search.emarefa.net/detail/BIM-460399
American Medical Association (AMA)
Ananthula, Suryatheja& Parajuli, Parash& Behery, Fathy A.& Alayoubi, Alaadin Y.& Nazzal, Sami& El Sayed, Khalid…[et al.]. δ-Tocotrienol Oxazine Derivative Antagonizes Mammary Tumor Cell Compensatory Response to CoCl2-Induced Hypoxia. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-460399
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-460399