Rutin Exerts Cytotoxic and Senescence-Inducing Properties in Human Melanoma Cells.

Iulia Pinzaru,Iasmina Marcovici,Dorina Coricovac,Razvan Susan,Denisa Predut,Doina Georgescu,Raul Chioibas,Cristina Dehelean

doi:10.3390/toxics9090226

Iulia Pinzaru, Iasmina Marcovici + Show 6 more

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https://doi.org/10.3390/toxics9090226

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Abstract

Malignant melanoma represents the deadliest type of skin cancer with narrow treatment options in advanced stages. Herbal constituents possessing anticancer properties occupy a particular spot in melanoma research as potential chemotherapeutics. Rutin (RUT) is a natural compound exerting antioxidant, antimicrobial, anti-inflammatory, UV-filtering, and SPF-enhancing activities that are beneficial to the skin; however, its effect as an anti-melanoma agent is less investigated. The current study is focused on assessing the cytotoxic potential of RUT against two different human melanoma cell lines: RPMI-7951 and SK-MEL-28 by evaluating its impact in terms of cell viability, cells’ morphology, and nuclear aspect assessment, and senescence-inducing properties. The results indicate a dose-dependent decrease in the viability of both cell lines, with calculated IC50 values of 64.49 ± 13.27 µM for RPMI-7951 cells and 47.44 ± 2.41 µM for SK-MEL-28, respectively, accompanied by a visible reduction in the cell confluency and apoptotic features within the cell nuclei. RUT exerted a senescence-inducing property highlighted by the elevated expression of senescent-associated beta-galactosidase (SA-β-gal) in SK-MEL-28 cells. Despite the in vitro anti-melanoma effect revealed by our results, further studies are required to elucidate the mechanisms of RUT-induced cytotoxicity and senescence in melanoma cells.

Highlights

Skin serves as the main physical, chemical, and immunological barrier against environmental noxious agents [1,2], as well as one of the most common routes of toxics’ entrance into the body [3]
The results indicate a dose-dependent decrease in the viability of both cell lines, with calculated IC50 values of 64.49 ± 13.27 μM for RPMI-7951 cells and 47.44 ± 2.41 μM for SK-MEL-28, respectively, accompanied by a visible reduction in the cell confluency and apoptotic features within the cell nuclei
RPMI-7951 cells are aAdhsearecnotmcpelolsnewnitthofatnheepainthtie-lmiael-llainkoemmaorpprhofoilloegoyf aRnUdTs,eavnereavlaclhuaantigoensowf eitrseiimdepnatcitfioedn tihnethmeoirrpmhoorlpoghyoloofgRyPaMndI-7co95n1fluanendcSeKf-oMlloEwL-i2n8gcReUllsThtaresabtemenenpte(rFfiogrumreed2.)R, sPuMchI-a7s95a1dcoesllesadreepaednhdeernetnrtecdeullcstwiointhoaf ncoenpflituheenlicael,llioksesmofoarpdhhoelroegnycea,nadndservoeuranldcihshancgeellsswweerreeiodbesnetrifvieedd imnatihneliyramt 1o0rpahnodlo50gyμMan.dAcsoimnfilluaernecffeecfot lwloaws dinegteRctUedT itnretahtemcaesnet o(Ff iSgKu-rMe E2)L,s2u8cchelalss, ahudmosaenmelanoma cells with a polygonal morphology, the most noticeable signs being recorded at the highest concentrations tested—10 and 50 μM (Figure 2)

Summary

Introduction

Skin serves as the main physical, chemical, and immunological barrier against environmental noxious agents [1,2], as well as one of the most common routes of toxics’ entrance into the body [3]. Carcinogenesis remains the most severe consequence of the prolonged exposure of the skin to environmental carcinogens. Several effective drugs are currently available for melanoma treatment [11], but due to the severe side effects and tumor resistance to therapy, the success rates remain low [12,13]. In this context, the discovery and development of improved treatment strategies are indispensable and demand continuous research. Natural compounds generally serve as potent anti-melanoma agents by initiating apoptosis and inhibiting cancer cell proliferation and metastasis [12]

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