Copyright by Pei Wang

Copyright
by
Pei Wang
2006

The Dissertation Committee for Pei Wang certifies that this is the approved
version of the following dissertation:
Studies of the Antitumor Activity of α-TEA in Human Breast
Cancer Cells
Committee:
Bob G. Sanders, supervisor
Kimberly Kline
Vishwanath R. Iyer
Jon M. Huibregtse
Theresa J O'Halloran

Studies of the Antitumor Activity of α-TEA in Human Breast
Cancer Cells
by
Pei Wang, B.S.
Dissertation
Presented to the Faculty of the Graduate School of
The University of Texas at Austin
in Partial Fulfillment
of the Requirements
for the Degree of
Doctor of Philosophy
The University of Texas at Austin
August 2006

iv
Acknowledgements
First I thank my supervisors, Drs. Bob G. Sanders and Kimberly Kline, for
their continuous scientific guidance, personal support, and encouragement
throughout my graduate studies. I am very lucky to have two great supervisors
like them.
I would also like to thank my committee members for their valuable
advice during my study. Thanks to Dr. Iyer for all the help on my microarray
study. Thanks to Dr. Huibregtse, and Dr. O’Halloran for their great scientific
suggestions.
I want to thank all my lab members. It has been a great pleasure to work
with such a nice group of researchers. Thanks to Li Jia, for her great help and
support both in my research and life. Thanks to Dr. Weiping Yu, for her scientific
suggestions and encouragement throughout my research. Thanks to Rachel M.
Snyder for her useful scientific discussions and help in animal research. Thanks to
Marla S. Menchaca for her continuous technical support in my research. Thanks
to Richa Tiwary, Dr. Ming-Chieh Shun, Wenjun Scott and Paul B. Latimer for
their help in my research. I also would like to thank John Mendenhall and Dr. Ti
Cao for their great help and useful suggestions in the nanoparticle study. Thanks
to Dr. Jian Gu for his generous help in the microarray study.
I sincerely thank my father, Baoquan Wang, my mother, Meiying Yao for
their selfishless love and life long support for my study. And last but not least, I
am very grateful to my husband, Zhanzhi Hu, for all his scientific suggestions,
encouragement and love.

v
Studies of the Antitumor Activity of α-TEA in Human Breast
Cancer Cells
Publication No._____________
Pei Wang, Ph.D.
The University of Texas at Austin, 2006
Supervisor: Bob G. Sanders
Breast cancer is the most common cancer among women and is the second
leading cause of cancer deaths among women in the United States. An effective
chemotherapeutic drug is greatly needed for breast cancer. In order to develop a
stable and clinically useful vitamin E-based chemotherapeutic agent, a
nonhydrolyzable ether linked acetic acid analogue of RRR-a-tocopherol, namely,
a-TEA has been produced. a-TEA exhibits strong antitumor activity in tumor
cells but has no effect on normal cells.
Since a-TEA is hydrophobic, formulation into appropriate carrier systems
to potentiate delivery is needed. The anticancer efficacy of a-TEA formulated into
liposomes or nanoparticles has been assessed in this study. a-TEA formulated in
either nanoparticles or liposomes at 5 mg/day was very effective in inhibiting