scholarly journals Inhibition of Pancreatic Cancer Cell-Induced Paracrine Hedgehog Signaling by Liver X Receptor Agonists and Oxy16, a Naturally Occurring Oxysterol

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Author(s):  
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Ziqiu Wang ◽  
Christina L Costantino ◽  
Agnieszka K Witkiewicz ◽  
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Author(s):  
Yusnita Rifai ◽  
Nurhaidah ◽  
Weltiansy Tanggulungan ◽  
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MMEO (3′-methoxy-3′,4″(methylenedioxy)-2,5-epoksilignan-4′ol-6-on) is a derivative of DMEO (3′-methoxy-3″,4″(methylenedioxy)-2,5-epoksilignan-4′,6-diol) synthesized through demethylation using dimethylsulfoxide-acetic anhydride reagent. MMEO inhibits Hedgehog signaling at a concentration of 4.1 μM. The current study aimed to formulate MMEO as solid dispersed nanoparticles and determine their physicochemical properties and inhibitory activities. XRD (X-ray diffraction) analysis showed that the crystalline particles of the pure compound MMEO was smaller than MMEO nanoparticles. Image J software showed that at concentrations of 25 mg/mL and 50 mg/mL, the average nanoparticle sizes were 852.26 nm and 178.65 nm, respectively. Therefore, the MMEO solid dispersion system with the PEG 4000 polymer increases the solubility of MMEO. The higher the concentration of PEG 4000 the greater the solubility of MMEO. Treating pancreatic cancer cell lines with MMEO silenced the smoothened function by downregulating mRNA Ptch expression. This study suggests that MMEO may inhibit pancreatic cancer disease.


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