Abstract

Multiple myeloma (MM) belongs to hematological cancers and its incidence is increasing worldwide. Despite recent advances in its therapy, MM still causes many deaths every year. In fact, current therapies sometimes fail and are associated with severe adverse effects, including neurotoxicity. As a part of our ongoing efforts to discover new potential therapies against MM, we prepared Hibiscus sabdariffa extracts obtained by a microwave-assisted solvent extraction and investigate their activity by in vitro assays on the RPMI-8226 cell line. The bioguided fractionation of the crude ethanolic extract allowed the identification of HsFC as the most effective extract. We assessed cell viability (MTT and Tripan blue test), cell migration (Boyden chamber assay), and neurotoxicity (DRG neurotoxicity assay). The promising results prompted us to further fractionate HsFC and we obtained two molecules effective against RPMI-8226 cells without neurotoxic effects at their active concentrations. Moreover, both compounds are able to significantly reduce cell migration.

Highlights

  • Multiple myeloma (MM) is a plasma cell neoplastic disorder causing severe bone pain and bone fractures, hypercalcemia, anemia, and kidney damage

  • Following a nature-aided drug discovery approach, we demonstrated the beneficial effects of Hibiscus sabdariffa Linn against MM [20]

  • C18 and Chromolith acid) adopting several gradient wereon tested on two different columns

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Summary

Introduction

Multiple myeloma (MM) is a plasma cell neoplastic disorder causing severe bone pain and bone fractures, hypercalcemia, anemia, and kidney damage. During the last five years, new1)targets in MM have been proposed as therapeutic options have recently been approved The main MM therapies consist of: molecules have recently been approved (Table 1) other therapies, including a peptide-based Alkylating agents such as MM melphalan andconsist other DNA are under validation [6]. FDA-approved proteasome inhibitor and represents one of the most important discoveries for been approved for clinical use: Bortezomib, Carfilzomib, and Ixazomib. Ofproteasome note, these agents can stimulate bone formation in MM [9]. Proteasome modulation can be achieved by employing small molecules such as lenalidomide, discoveries for fighting MM of recent years Of note, these agents can stimulate bone formation structurally related thalidomide and actingcan as be.

Molecular
Results and discussion
In vitro
Trypan
Effect of of cells treated Dashed with HsFC
Cell viability and neurotoxicity treatment with Hib-ester and
Conclusions
Methods
Instruments
Plant Material and Extraction Procedure
Extract Fractionation and Analysis
Cell Culture
MTT Assay
Trypan Blue Vital Count
Boyden Chamber Assay
DRG Neurotoxicity Assay
Statistical Analysis
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