<p>Dehydrocorydaline inhibits cell proliferation, migration and invasion via suppressing MEK1/2-ERK1/2 cascade in melanoma</p>

Abstract

Purpose: Alkaloids are naturally occurring chemical compounds that are widely distributed in plants, and have pharmaceutical values and low toxicity. In recent years, some of them have been demonstrated to be promising therapeutic drug candidates for cancer treatment. Herein, we tried to explore the antitumor effect of dehydrocorydaline (DHC), a natural alkaloid isolated from Corydalis , on malignant melanoma. Methods: We treated two malignant metastatic melanoma cell lines, A375 and MV3, and a normal melanocyte cell line, PIG1, with various concentrations of DHC for set amounts of time, and detected cell proliferation, migration, and invasion by using MTT, BrdU, transwell, Western blot and soft agar assay in vitro and tumorigenicity in the xenografts in vivo. Results: Our results showed that DHC dramatically blocked cell proliferation and led to cell cycle arrest at G0/G1 phase and downregulated the expressions of cell cycle regulators CDK6 and Cyclin D1 in melanoma cells. However, DHC had little inhibitory effect on normal melanocyte cell line PIG-1. Meanwhile, DHC suppressed cell invasion and migration through modulating the epithelial–mesenchymal transition (EMT) markers including E-cadherin, vimentin, as well as β-catenin. In addition, DHC also significantly attenuated tumor growth in vivo. The expressions of cell cycle-related and metastasis-related proteins were further confirmed by immunohistochemical staining in the xenografts. Importantly, MEK1/2-ERK1/2 cascade was inactivated after DHC treatment and ERK activator t-butylhydroquinone (tBHQ) treatment rescued DHC-induced cell proliferation inhibition. Conclusions: Our results indicated that DHC inhibited cell proliferation and migration/invasion via inactivating MAPK signaling, and showed that DHC might be a potential novel drug to treat malignant melanoma.

Melatonin inhibits gallbladder cancer cell migration and invasion via ERK‑mediated induction of epithelial‑to‑mesenchymal transition

“…To verify the role of the ERK signaling pathway in regulating the migratory potential and EMT, tBHQ (an activator of ERK1/2) was added to GBC cells ( 18 – 20 ). Notably, tBHQ (50 µM) reversed the effects of melatonin in inhibiting phosphorylation of ERK ( Fig.…”

LncRNA LINC00662 promotes colon cancer tumor growth and metastasis by competitively binding with miR-340-5p to regulate CLDN8/IL22 co-expression and activating ERK signaling pathway

“…ERK signaling pathway is involved in the regulation of cell proliferation, differentiation and apoptosis. Activated ERK signaling pathway promotes the occurrence and development of a variety of cancers [18,19]. mRNAs, miRNAs, lncRNAs and circRNAs affect the occurrence and development of cancer by regulating the activation of ERK signaling pathway.…”

Upregulation of deubiquitinase USP7 by transcription factor FOXO6 promotes EC progression via targeting the JMJD3/CLU axis

“…After 24 h, cells were cultured in fresh medium containing 1 μg/mL puromycin for 48 h. Seven days later, colonies were selected and JMJD3 knockout efficiency was detected by western blot analysis. 38 The sequences were as follows: JMJD3-gRNA1.1, 5′-CACCTGTGGATGTTACCCGCATGA-3′; JMJD3-gRNA1.2, 5′-AAACTCATGCGGGTAACATCCACA-3′; JMJD3-gRNA2.1, 5′-CACCGTCCCTGGCAGCCGAACGCC-3′; and JMJD3-gRNA2.2, 5′-AAACGGCGTTCGGCTGCCAGGGAC-3′.…”