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
Authors: Chu, Yafei; Xiao, Zheng; Jing, Nan; Yan, Wenjuan; Wang, Shanmei; Ma, Bing; Zhang, Jiangfeng; Li, Yi
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 mu M), BGC-823 (IC50 = 7.26 mu M), MGC803 (IC50 = 4.75 mu M), SGC-7901 (IC50 = 1.96 mu M), HGC-27 (IC50 = 5.70 mu M), SGC-7901/ADR (IC50 = 0.24 mu M), SGC-7901/VCR (IC50 = 1.09 mu M), and MGC803/PTX (IC50 = 1.32 mu M) 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 effective treatment for gastric cancer and adriamycin-resistant gastric cancer.
Prognostic Relevance of HJURP Expression in Patients with Surgically Resected Colorectal Cancer
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Kang, Dong Hyun; Woo, Jongsoo; Kim, Hyeongjoo; Kim, Soo Youn; Ji, Sanghee; Jaygal, Gunn; Ahn, Tae Sung; Kim, Han Jo; Kwak, Hyoung Jong; Kim, Chang-Jin; Baek, Moo-Jun; Jeong, Dongjun
Abstract
HJURP is a key factor for CENP-A deposition and maintenance in centromeres. The role of mis-regulation of histone chaperones in cancer initiation and progression has been studied. However, its role in colorectal cancer is still unclear. In this study, we aimed to evaluate the expression of HJURP in 162 colorectal cancer tissue. To investigate the function of HJURP in the colorectal cancer cell, we suppressed HJURP expression by siRNA and confirmed proliferation, migration, invasion, and anchorage independent of colony forming ability. The association between HJURP expression levels and clinicopathological factors was evaluated in 162 CRC tissues using immunohistochemistry. The overall survival rate in patients of HJURP high expression was higher than those in HJURP low expression in CRC. Suppressing HJURP expression decreased cellular proliferation, invasion, and migration in four CRC cell lines: HT29, HCT116, SW480, SW620 in vitro study. Our findings revealed that the knockdown of HJURP suppressed the proliferation, migration, invasion, and tumorigenicity in CRC cells. Due to its strong association with CRC, HJURP could be a potential prognostic biomarker and a novel target for drug discovery.