Arborinine, a potential LSD1 inhibitor, inhibits epithelial-mesenchymal transition of SGC-7901 cells and adriamycin-resi
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PRECLINICAL STUDIES
Arborinine, a potential LSD1 inhibitor, inhibits epithelial-mesenchymal transition of SGC-7901 cells and adriamycin-resistant gastric cancer SGC-7901/ADR cells Yafei Chu 1 & Zheng Xiao 1 & Nan Jing 1 & Wenjuan Yan 1 & Shanmei Wang 1 & Bing Ma 1 & Jiangfeng Zhang 1 & Yi Li 1 Received: 7 July 2020 / Accepted: 29 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary 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 epithelialmesenchymal 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 effective treatment for gastric cancer and adriamycin-resistant gastric cancer. Keywords Arborinine . Gastric cancer . Adriamycin-resistant gastric cancer . LSD1 . Epithelial-mesenchymal transition
Introduction Gastric cancer is one of the most common malignant tumors in the world and a leading cause of cancer-related death [1]. Chemotherapy plays a critical role in the comprehensive treatment of gastric cancer, while it faces some challenges (e.g., drug resistance) [2]. Multidrug resistance has become a significant obstacle to the success of chemotherapy for patients with gastric cancer [3]. For chemotherapy-resistant gastric cancer, epithelial-mesenchymal transformation (EMT) is the main factor leading to an invasive phenotype [4]. Therefore, there is an urgent need to discover novel drugs with significant antitumor activity against gastric cancer and chemotherapyresistant gastric cancer.
Yafei Chu and Zheng Xiao contributed equally to this work. * Yi Li [email protected] 1
Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou 450003, China
Natural products are highly specific to cancer cells without substantial toxicity to normal cells. Therefore, they have great potential to be used in clinical trials as anticancer agents [5]. Arborinine, a natural product isolated from G. parva leaf extracts, exhibits potential antibacterial, anti-hepatitis C virus, and antica
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