Englerin A Selectively Induces Necrosis in Human Renal Cancer
Cells |
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Authors: | Florian J Sulzmaier Zhenwu Li Mika L Nakashige David M Fash William J Chain Joe W Ramos |
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Institution: | 1. Cancer Biology Program, University of Hawaii
Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, United States of
America.; 2. Department of Chemistry, University of Hawaii
at Manoa, Honolulu, Hawaii, United States of America.; 3. Department of Molecular Biosciences and
Bioengineering, University of Hawaii at Manoa, Honolulu, Hawaii, United States
of America.; The Ohio State University, United States of
America, |
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Abstract: | The number of renal cancers has increased over the last ten years and patient
survival in advanced stages remains very poor. Therefore, new therapeutic
approaches for renal cancer are essential. Englerin A is a natural product with
a very potent and selective cytotoxicity against renal cancer cells. This makes
it a promising drug candidate that may improve current treatment standards for
patients with renal cancers in all stages. However, little is known about
englerin A''s mode of action in targeting specifically renal cancer cells.
Our study is the first to investigate the biological mechanism of englerin A
action in detail. We report that englerin A is specific for renal tumor cells
and does not affect normal kidney cells. We find that englerin A treatment
induces necrotic cell death in renal cancer cells but not in normal kidney
cells. We further show that autophagic and pyroptotic proteins are unaffected by
the compound and that necrotic signaling in these cells coincided with
production of reactive oxygen species and calcium influx into the cytoplasm. As
the first study to analyze the biological effects of englerin A, our work
provides an important basis for the evaluation and validation of the
compound''s use as an anti-tumor drug. It also provides a context in which
to identify the specific target or targets of englerin A in renal cancer
cells. |
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