Amin, J

Chiarelli, R

Librizzi, M

Longo, A

Luparello, C

Spencer, J

Tobiasch, E

LIBRIZZI, Mariangela

LONGO, Alessandra

CHIARELLI, Roberto

LUPARELLO, Claudio

Archivio istituzionale della ricerca - Università di Palermo

;/ri;!i;if i+;r,ffi86' CONGRESSO NAZIONALE SIBS - PALERMO 24-25 OTTOBRE 2013P6O - JAHA, A NOVEL HISTONE DEACETYLASE INHIBITOR: CYTOTOXICEFFECT ON TRIPLE.NEGATIVE BREAST CANCER CELLSM.L1bizzil, A. Longol, R.chiarellil, J.Amin2, J. spencer3, E. Tobias cha,c.Luparellol1 .Dipartimento STEB ICEF, Università di palermo,2. School of Science at Medway, University of Greenwich (UK),3.Department of Chemistry, University of Sussex (UK)4.Department of Natural Sciences, University of Applied Science, Bonn-Rhein-Sieg (D)Corresponding Author: Prof. Claudio Luparello: Dipartimento di Scienze à TecnologieBiologiche, Chimiche e Farmaceutiche. Università degli Studi di Palermo, Viale delle ScienzeEd.\ 6, Palermo, Italy tel : 09 123897 405 e-mail : claudio.luparello @ unipa.itHistone deacetylase inhibitors (HDACi) have emerged as effective anticancer agents in theclinical practice. Jay Amin hydroxamic acid (JAHA), is a metal-based analogue olthe HDACisuberoylanilide hydroxamic acid SAHA [1] obtained by the formal replacemLnt by a ferrocenebioisostere of the aryl cap in SAHA. In the present study, the effects oi faga on MDA-M8231cells, obtained from triple-negative human breast carcinoma, were evaluated. JAHA exhibitshigh cytotoxic activity on breast cancer cells, with an ICso = g.45 pM at 72 h. Followingtreatment with JAHA at this concentration, the viability of MDA-M8231 cells was analyzeausing an MTT assay, and apoptosis onset, alteration of cell proliferativ e rate, intracellularreactive oxygen species (ROS) generation and mitochondrial membrane potential (Aym)alteration, if occurring, were evaluated by flow cytometry t2]. h addition, Wesiern blot anatysiswas performed to examine the expression of autophagy-associated proteins. The resultsdemonstrated that treatment with JAHA induced a nòn-upoptotic type àf ce1 death, and analteration of cell proliferation characterizedby the accumulation of cèfls in the G1 and subGophases of the cycle. The most interesting results on JAHA mechanism of action regard its abilityto induce early ROS production and subsequent dissipation of AYm and autophagy irhibitior,that were confirmed by the reversion of the cytotoxic effect obtained by co-treatment with eitheranti-oxidant (butylated hydroxytoluene) or autophagy-promoter compound (rapamycin). An invitro "scratch assay" has also been performed to measure migration of cells treated for Z4h with8.45 pM JAHA compared to control. Preliminary indications suggest ttrat JAHA has no effect onthe motile behaviour of MDA-MB231 breast cancer cells. In lighi of such results, it appears thatJAHA may be a promising potential chemotherapeutic agent foi triple-negative breast cancer.fle work was supported by University of Palermo (R.S. ex60Vo and f.f'n ZOt:) and progettoVigoni 20ll for Claudio Luparello, and BMBF, AdiPaD, L72OXO6, FHprofUnt, ÉKZ,03FH012PB2; FH-Extra,FKZ 21112frt012; DAAD, PPP Vigoni,FKZ:546692i8;BMBF-AIF,FKZ: 1720X06; and Geràteprograrun, Fachhochschulen NRW 2008 for Edda Tobiasch.I Spencer J, Amin J, Wang M, Packham G, Alwi SS, Tizzard GJ, Coles SJ, paranat RM.Bradner JE, Heightman TD. Synthesis and biological evaluation of JAHAs: feoo"ene$aseÉclass I tristone deacetylase inhibitors. ACS Med chem Lettz}ll;2: 35g-62.2. Llb.'izzi M, Longo A, Chiarelli R, Amin J, Spencer J, Luparello C. Cytotoxic effects ofJay Amin hydroxamic acid (JAHA), a ferrocene-basèa class I histone deacetylase inhibitdr, ontriple-negative MDA-MB231 breast cancer cells. Chem. Res. Toxicol. 20lZ; Zi:260g-2616.757

JAHA, a novel histone deacetylase inhibitor: cytotoxic effect on triple-negative breast cancer cells

https://iris.unipa.it/retrieve/handle/10447/86705/93224/abstract%20SIBS.pdf

JAHA, a novel histone deacetylase inhibitor: cytotoxic effect on triple-negative breast cancer cells

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Archivio istituzionale della ricerca - Università di Palermo