 Abstract:
Ovarian cancer is the fifth leading cause of death for women in the
Western world. The major challenge in ovarian cancer treatment is
its broad resistance to available chemotherapeutic drugs. Therefore,
new approaches in the treatment of ovarian cancer are needed.The
long-term objective of this proposal is to provide a better
understanding of the molecular mechanism of ovarian tumorigenesis
and angiogenesis in response to ROS/antioxidant signaling pathway,
and provide novel signaling pathways necessary for establishing
therapeutic strategies using antioxidants for human ovarian cancer
in the future. Reactive oxygen species (ROS) including H2O2, O2.-
and OH. are generated by cellular aerobic metabolism and are induced
by heavy metals, growth factors, and cytokine. Recent studies
indicated that ROS are involved in the development and growth of
human cancers. Apigenin is a nontoxic bioflavonoid antioxidant,
recently shown to have anticancer effects in several different
cancer cell lines. It is known that flavonoid compounds from fruits
and vegetables have protective effects against lung, colon, breast,
prostate, bladder, and stomach cancer. Our preliminary studies
showed that apigenin decreased ovarian cancer cell proliferation and
tumor growth. However, the molecular mechanism of apigenin in
inhibiting human cancer cells remains to be defined. We hypothesize
that apigenin inhibits ovarian tumor growth and angiogenesis by
inhibiting several key signaling pathways in the ovarian cancer
cells. Specific Aim 1 is designed to determine whether apigenin
inhibits several major signaling pathways, and the molecular
mechanism of apigenin in inhibiting the specific signaling pathways
in ovarian cancer cells. Specific Aim 2 is to determine which
signaling pathways are inhibited by apigenin in affecting ovarian
cancer cell proliferation and tumor formation, and identify the
specific signaling molecules that are essential downstream molecules
inhibited by apigenin for affecting ovarian cell proliferation and
tumor growth. Specific Aim 3 is to analyze whether apigenin inhibits
ovarian tumor angiogenesis, and identify which signaling molecules
mediate apigenin-inhibiting tumor angiogenesis. This work will
identify molecular mechanism of apigenin in inhibiting ovarian cell
proliferation, tumor growth, and angiogenesis; and help to establish
rational therapeutic strategies for ovarian cancer using apigenin in
the future.
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