Anti-Multiple Myeloma Potential of Secondary Metabolites from Hibiscus sabdariffa-Part 2.

Alessio Malacrida,Stefano Alcaro,Mariarosaria Miloso,Valeria Cavalloro,Emanuela Martino,Arianna Cassetti,Roberta Rigolio,Giosuè Costa,Simona Collina,Francesca Alessandra Ambrosio

doi:10.3390/molecules26216596

Abstract

Multiple Myeloma (MM) is an aggressive tumor causing millions of deaths every year and currently available therapies are often unsuccessful or correlated with severe side effects. In our previous work we demonstrated that the Hibiscus sabdariffa hydroalcoholic extract inhibits the growth of the MM cell line and we isolated two metabolites responsible for the activity: Hib-ester and Hib-carbaldehyde. Herein we report their interaction with proteasome, one of the main targets in the fight against MM. The molecular modelling study outlined a good interaction of both compounds with the target and these results prompted us to investigate their potential to inhibit proteasome. Metabolites were then isolated from the calyces and an extract with a high content of Hib-ester and Hib-carbaldehyde was prepared. An anticancer profile was drawn, evaluating apoptosis, autophagy and proteasome inhibition, with the anticancer properties being mainly attributed to the Hib-ester and Hib-carbaldehyde, while the proteasome inhibition of the extract could also be ascribed to the presence of anthocyanins, a class of secondary metabolites already known for their proteasome inhibitory activity.

Highlights

Multiple myeloma (MM) is a neoplastic disease causing renal dysfunction, hypercalcemia and lytic lesions in the bone [1,2]
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Summary

Introduction

Multiple myeloma (MM) is a neoplastic disease causing renal dysfunction, hypercalcemia and lytic lesions in the bone [1,2]. About 80% of patients at the time of diagnosis are affected by myeloma bone disease (MBD), caused by an imbalance of the bone remodeling process in the bone marrow microenvironment. This imbalance induces the formation of osteolytic lesions that reduce bone structural integrity and often culminate in pathological fractures. Despite different therapeutic options that are available, MM is considered an unmet neoplastic disease since it causes millions of deaths every year. Drugs currently availDabelsepioteftdeniffelreeandt tthoerdarpueguticreospisttiaoncsethaant dareseavvearielabslied,eMeMffeicstcso, ntshiedreerfeodrea,nsupnemcifeitc ntheeorpalpaestuicticdiospetaisoensifnocreMitBcDautsheastmarielliaobnles toof sdteimatuhlsaeteveorsyteyoebalra.sMticoarcetoiveitry, dcoruuglds rceuprrensetlnyt avnaiimlabploerotaftnetnsulepapdotrotidvreusgtraetseisgtyantocetraenadt sMevMer.e side effects, specific therapeutic optioTnos fodraMteB, Dthtehagt oalrde asbtlaentdoasrtdimuthlaetreaposietesobolfasMticMactairveitydcrouuglsd raecptirnegsenatsanprimotpeaosrotamnte sinuhpipboitrotirvse. sPtrroateagsyotmoetreisataMmMu.lticatalytic complex responsible for 80–90% of protein degraTdoadtaioten,.tIhteisgoaldsostiannvdoalvrdedthienrathpeieds eogfrMadMataiorne dorfuIgksBa, ctthineginahsipbirtootreaosfonmueclienahribfaitcotrosr

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Conclusion