Lupeol inhibits migration and invasion of colorectal cancer cells by suppressing RhoA-ROCK1 signaling pathway
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ORIGINAL ARTICLE
Lupeol inhibits migration and invasion of colorectal cancer cells by suppressing RhoA-ROCK1 signaling pathway Yiwen Jiang 1 & Dan Hong 1 & Zhefeng Lou 1 & Xuezi Tu 1 & Longjin Jin 1 Received: 4 September 2019 / Accepted: 8 January 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Metastasis is the main cause of death in colorectal cancer (CRC) patients. However, current treatment options for CRC metastasis are very limited. Lupeol, a triterpene that is widely found in vegetables and fruits, has been reported to possess the cancerpreventive and anti-inflammatory functions. However, the roles of Lupeol in the migration and invasion of colorectal cancer remain unclear. Here, we evaluated the effect of Lupeol treatment on colorectal cancer cell lines, HCT116 and SW620, and delineated its underlying mechanisms. Our results showed that Lupeol induced a dose-dependent inhibition of HCT116 and SW620 cells viability, measured by CCK8 assay. Wound healing and Transwell migration and invasion assays revealed that Lupeol significantly suppressed the migration and invasion of CRC cells. Using laser confocal microscope, we observed that the pseudopods and protrusions of HCT116 and SW620 cells decreased and disrupted after treatment with Lupeol. In addition, the quantitative real-time PCR and Western blotting results showed that Lupeol downregulated the expression of RhoA and RhoC, and their downstream effectors ROCK1, Cofilin, p-MLC, and the associated regulatory protein Cyclin A2. Interestingly, the migration and invasion capacity of CRC cells was reduced after RhoA knockdown. And there were no additional changes in CRC cells with RhoA knockdown to treat with Lupeol. These findings demonstrate that Lupeol can suppress the migration and invasion of colorectal cancer cells by remodeling the actin cytoskeleton via RhoA-ROCK1 pathway inhibition, which may provide an effective anti-metastatic agent for CRC patients. Keywords Lupeol . RhoA-ROCK1 signaling pathway . Colorectal cancer . Migration and invasion . Cytoskeleton
Introduction Colorectal cancer (CRC) is one of the most common and lethal digestive malignancies in the world. According to the Global cancer statistics of 2018, colorectal cancer ranked the second in terms of mortality and the third in terms of incidence (Freddie et al. 2018; Siegel et al. 2019). Cancer metastasis, which remains incurable, is the leading cause of CRC-related death (Peddareddigari et al. 2010; Tauriello et al. 2018). Around 25% of CRC patients are diagnosed with tumor metastasis at initial diagnosis, and half of them develop metastases (Shelton et al. 2018; Van et al. 2014). However, chemotherapy drugs currently used to fight against CRC are usually along with side effects and multidrug resistance. Therefore, * Longjin Jin [email protected] 1
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325000, China
new effective potential therapeutic agents to target CRC metastasis are urgently needed. In the past few years, natural
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