Anti-endometrial Cancer Activity of Hedyotis diffusa Willd and its Phytochemicals by Experimental and In Silico Analysis
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Abstract
Hedyotis diffusa Willd (HDW) injection is a clinically approved herbal medicine for various cancer therapies in China. This study aims to investigate HDW injection on endometrial cancer (EC), which is currently not an indication of HDW. Cytotoxicity and flow cytometric analysis were employed to study the inhibition and apoptosis of EC cells under various concentrations of HDW injection, cisplatin, and their combination. In silico docking simulations were used to predict the binding affinities between the phytochemicals of HDW and the EC therapeutic target, A3 adenosine receptors (A3ARs). FAF-Drugs 4 was used to study the drug-like properties of the phytochemicals. The HDW injection inhibited the growth and caused apoptosis of EC cells. HDW and cisplatin produced more potent inhibition effects than their individual use. The phytochemicals 5-demethylsinensetin, 5-demethylnobiletin and 5-hydroxy-6,7,3,4-quatermethoxyflavonoid obtained the highest docking score with acceptable drug-like properties for oral administration. The HDW injection and the in silico identified A3ARs inhibitors have a high potential for further investigations to develop an effective and safe EC treatment.
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