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allied
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Journal of Biotechnology and Phytochemistry
Volume 1 Issue 3
Chemistry World 2017
Notes:
Page 26
November 13-15, 2017 Athens, Greece
7
th
World Congress on
Chemistry
small molecule inhibitor of Hsp70 has cytotoxicity
against various cancers
Injae Shin
Yonsei University, Korea
H
sp70 acts as an anti-apoptotic factor and protects cells
from various apoptotic stresses. Hsp70 is highly expressed
in many cancer cells and its overexpression correlates with
tumor development and resistance to chemotherapy. By using
cell-based, high-throughput screening of an imidazole library
and target identification with affinity chromatography, a small
molecule named apoptozole (Az) that inhibits Hsp70 activity was
discovered. This substance inhibits Hsp70 activity by binding to
its ATPase domain but does not affect other heat shock proteins
such as Hsp40, Hsp60, and Hsp90. We also conducted structure-
activity relationship study. Treatment of cells with Az induces an
array of apoptotic phenotypes in various cancer cell lines. The
inhibitor blocks the interaction of Hsp70 with Apaf-1 but does
not affect the interaction of Hsp70 with ASK1, JNK, Bax, and
AIF, thereby inducing caspase-dependent apoptosis. In addition,
the inhibitor remarkably reduces tumors in nude mouse models
xenografted with cancer cells without affecting the viability.
Interestingly, treatment of cancer cells and tumor-xenografted
mice with a combination of a Hsp70 inhibitor and doxorubicin
enhances apoptosis in comparison with a single treatment with
either doxorubicin or the inhibitor. I will discuss the current
progress made in Az-induced cancer cell death.
Biography
Injae Shin received his BS degree in 1985 and MS degree in Chemistry from
Seoul National University, Korea in 1987. His PhD research was performed
at University of Minnesota from 1991-1995 and his Postdoctoral studies at
University of California at Berkeley from 1995-1998. He is a Director of Center
for Biofunctional Molecules and an Underwood Distinguished Professor at
Yonsei University. His research interests include the synthesis of biologically
and chemically interesting compounds, the development of bioactive molecules
that can be used for biological and biomedical studies, and functional studies of
glycans using chemical tools including glycan microarrays.
injae@yonsei. ac.
Injae Shin, J Biotech and Phyto 2017