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

Nadire Özenver,Thomas Efferth,Edmond Fleischer,Anette Klinger,Mona Dawood

doi:10.3390/molecules25143224

Nadire Özenver, Thomas Efferth + Show 3 more

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https://doi.org/10.3390/molecules25143224

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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 log10IC50 values for secalonic acid. In conclusion, the present study supports the therapeutic potential of SAF to treat multiple myeloma.

Highlights

IntroductionThe second leading cause of death globally, caused 9.6 million deaths in 2018 worldwide [1]
Cancer, the second leading cause of death globally, caused 9.6 million deaths in 2018 worldwide [1].Currently, the 5-year survival rate of patients receiving cancer therapy is 67% [2,3]
In the present study secalonic acid F (SAF) was tested for the first time against several multiple myeloma cells with a focus on determining its mechanism of action

Summary

Introduction

The second leading cause of death globally, caused 9.6 million deaths in 2018 worldwide [1]. The 5-year survival rate of patients receiving cancer therapy is 67% [2,3]. In 2014, 14.5 million cancer patients survived their disease in the United States and the number of cancer survivors is considered to reach 19 million by 2024 [4]. Multiple myeloma (MM) is an incurable disease leading 1% of all cancers and 10% of hematological malignancies with low survival rates worldwide [5,6]. Newly developed drugs such as proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents have extended patient survival up to 5–6 years following diagnosis [9,11]

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