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Heptelidic acid displays cytotoxicity against rhabdoid tumor of the kidney in vitro

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Abstract

Rhabdoid tumor of the kidney (RTK) is a rare but aggressive cancer that occurs in infancy and early childhood.[1] Current treatment protocols for RTK included a combination of surgery, radiation therapy, and chemotherapy, however the prognosis remains poor with a 5-year survival between 20-25%.[1] Therefore, the need to develop therapeutic strategies to treat RTK is still greatly unmet. High dependence on glycolysis by cancer cells, known as the Warburg effect [2], demonstrates a weakness that can be harnessed to target cancer cells and provides rationale for exploring antiglycolytic approaches for targeting cancer cells. Glyceraldehye-3-phosphate dehydrogenase (GAPDH) is an essential enzyme within the glycolysis pathway (Figure 1) making GAPDH a potential therapeutic target for inhibiting tumor growth and progression [3]. Aspergillus oryzae is a probiotic fungus that is used in the production of Japanese fermented food, including soybean paste and soy sauce. Heptelidic acid (HA) is a sesquiterpene lactone derived from A. oryzae and has recently been shown to exert antitumor effects against multiple cancers including pancreatic and extraintestinal melanomas. [4,5] HA is a specific and irreversible inhibitor of GAPDH.[6] Its GAPDH inhibition activity is shown to contribute to its antitumor effects. [4,5]. The purpose of this study is to assess the therapeutic potential of HA on RTK. This study gives the first evidence that HA shows cytotoxicity in RTK and provides rationale to ultimately develop a therapy using HA for RTK.

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