Arborinine, a potential LSD1 inhibitor, inhibits epithelial-mesenchymal transition of SGC-7901 cells and adriamycin-resistant gastric cancer SGC-7901/ADR cells.

Investigational New Drugs
Yafei ChuYi Li

Abstract

Arborinine is a natural product isolated from G. parva leaf extracts, which displays potentially antiproliferative activity against human cervical cancer cells. In contrast, its anticancer effects against gastric cancer cells and drug-resistant gastric cancer cells remain unknown. In this work, arborinine was evaluated as a broad-spectrum antiproliferative agent, and it exhibited potently inhibitory activity against NCI-N87 (IC50 = 5.67 μM), BGC-823 (IC50 = 7.26 μM), MGC803 (IC50 = 4.75 μM), SGC-7901 (IC50 = 1.96 μM), HGC-27 (IC50 = 5.70 μM), SGC-7901/ADR (IC50 = 0.24 μM), SGC-7901/VCR (IC50 = 1.09 μM), and MGC803/PTX (IC50 = 1.32 μM) cell lines. Subsequent target verification experiments demonstrated that arborinine selectively and reversibly inhibited LSD1 in a time-dependent manner. Furthermore, it was found that arborinine suppressed the epithelial-mesenchymal transition of gastric cancer cell line SGC-7901 and adriamycin-resistant gastric cancer cell line SGC-7901/ADR in a dose-dependent manner. The in vivo antitumor study further indicated that arborinine can significantly reduce the growth of tumors both in SGC-7901 and SGC-7901/ADR xenograft mouse models. Overall, we demonstrated the potential of arborinine as an effect...Continue Reading

References

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