Chemometric and Transcriptomic Profiling, Microtubule Disruption and Cell Death Induction by Secalonic Acid in Tumor Cells

化学计量学和转录组学分析、塞卡洛酸对肿瘤细胞微管破坏和细胞死亡的诱导作用

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Abstract

Nature is an indispensable source of new drugs, providing unique bioactive lead structures for drug discovery. In the present study, secalonic acid F (SAF), a naturally occurring ergochrome pigment, was studied for its cytotoxicity against various leukemia and multiple myeloma cells by the resazurin assay. SAF exhibited cytotoxic activity on both leukemia and multiple myeloma cells. Generally, multiple myeloma cells were more sensitive to SAF than leukemia cells. NCI-H929 cells were the most affected cells among the tested panel of multiple myeloma cell lines and were taken for further studies to assess the mode of action of SAF on those cells. Cell cycle analysis revealed that SAF induced S and G2/M arrest in NCI-H929 cells. SAF-associated apoptosis and necrosis resulted in cytotoxicity. SAF further inclined the disassembly of the tubulin network, which may also account for its cytotoxicity. COMPARE and hierarchical cluster analyses of transcriptome-wide expression profiles of the NCI tumor cell line panel identified genes involved in numerous cellular processes (e.g., cell differentiation, cell migration, and other numerous signaling pathways) notably correlated with log(10)IC(50) values for secalonic acid. In conclusion, the present study supports the therapeutic potential of SAF to treat multiple myeloma.

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