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open access
Review
A diagnosis of advanced ovarian cancer is the beginning of a long and arduous journey
for a patient. Worldwide, approximately half of the individuals undergoing therapy
for advanced cancer will succumb to the disease, or consequences of treatment. Well-known
and widely-used chemotherapeutic agents such as cisplatin, paclitaxel, 5-fluorouracil,
and doxorubicin are toxic to both cancer and non-cancerous cells, and have debilitating
side effects Therefore, development of new targeted anticancer therapies that can
selectively kill cancer cells while sparing the surrounding healthy tissues is essential
to develop more effective therapies. We have developed a new class of synthetic curcumin
analogs, diarylidenyl-piperidones (DAPs), which have higher anticancer activity and
enhanced bio-absorption than curcumin. The DAP backbone structure exhibits cytotoxic
(anticancer) activity, whereas the N-hydroxypyrroline (-NOH) moiety found on some
variants functions as a cellular- or tissue-specific modulator (antioxidant) of cytotoxicity.
The anticancer activity of the DAPs has been evaluated using a number of ovarian cancer
cell lines, and the safety has been evaluated in a number of non-cancerous cell lines.
Both variations of the DAP compounds showed similar levels of cell death in ovarian
cancer cells, however the compounds with the -NOH modification were less toxic to
non-cancerous cells. The selective cytotoxicity of the DAP--NOH compounds suggests
that they will be useful as safe and effective anticancer agents. This article reviews
some of the key findings of our work with the DAP compounds, and compares this to
some of the targeted therapies currently used in ovarian cancer therapy.
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