Identification of Carpesium cernuum extract as a tumor migration inhibitor based on its biological response profiling in breast cancer cells.

Abstract

BACKGROUND\nBreast cancer is one of the most lethal cancers in women when it reaches the metastatic stage. The plant Carpesium cernuum has been used as an anti-inflammatory, analgesic, and detoxifying agent in Chinese folk medicine. However, the inhibitory activity and molecular mechanisms of Carpesium cernuum in breast cancer cells have not been investigated.\n\n\nMETHODS\nRNA sequencing experiments were performed to elucidate the cellular pathways affected by Carpesium cernuum extract (CCE). Cell viability and EdU incorporation assays were conducted to determine the effect of CCE on cell proliferation. The inhibitory effects of CCE on the expression levels of target genes were confirmed by qRT-PCR and Western blot. Cell migration and invasion were analysed with transwell chamber assays.\n\n\nRESULTS\nProliferation assays indicated that CCE inhibited cell proliferation in multiple cancer cell lines and the IC50 value of CCE was the smallest in MDA-MB-231 cells. Transcriptome analysis showed that CCE significantly affected the cell adhesion pathway. Further experiments revealed that CCE suppressed cell migration and invasion. The inhibitory effect on migration was likely mediated by targeting TIMP1, MMP9, CD44 and COL4A2. The main active components of CCE were isolated, and CCE-derived sesquiterpene lactone substances could reproduce the inhibitory effect of CCE on cell migration and invasion.\n\n\nCONCLUSIONS\nOverall, both molecular and phenotypic assays showed that CCE has potential in the treatment of breast cancer, especially for the treatment of breast cancer metastasis. CCE-derived sesquiterpene lactone substances are the foundation for the tumor inhibitory effect of CCE.