Anti-proliferative, pro-apototic and anti-migratory properties of HDAC inhibitor PXD-101 on osteosarcoma cell lines

Michela Rossi; Viviana De Martino; Laura Di Giuseppe; Giulia Battafarano; Jacopo Di Gregorio; Sara Terreri; Francesco Marampon; Salvatore Minisola; Andrea Del Fattore

doi:10.1016/j.abb.2022.109489

Anti-proliferative, pro-apototic and anti-migratory properties of HDAC inhibitor PXD-101 on osteosarcoma cell lines

Arch Biochem Biophys. 2023 Jan 15:734:109489. doi: 10.1016/j.abb.2022.109489. Epub 2022 Dec 13.

Authors

Michela Rossi¹, Viviana De Martino², Laura Di Giuseppe³, Giulia Battafarano⁴, Jacopo Di Gregorio⁵, Sara Terreri⁶, Francesco Marampon⁷, Salvatore Minisola⁸, Andrea Del Fattore⁹

Affiliations

¹ Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, viale San Paolo 15, 00146, Rome, Italy. Electronic address: michela1.rossi@opbg.net.
² Department of Clinical, Internal, Anaesthesiological and Cardiovascular Sciences, "Sapienza" University, viale del Policlinico 155, 00161, Rome, Italy. Electronic address: viviana.demartino@uniroma1.it.
³ Department of Clinical, Internal, Anaesthesiological and Cardiovascular Sciences, "Sapienza" University, viale del Policlinico 155, 00161, Rome, Italy. Electronic address: laura.digiuseppe14@gmail.com.
⁴ Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, viale San Paolo 15, 00146, Rome, Italy. Electronic address: giulia.battafarano@opbg.net.
⁵ Department of Clinical, Internal, Anaesthesiological and Cardiovascular Sciences, "Sapienza" University, viale del Policlinico 155, 00161, Rome, Italy. Electronic address: jacopodigregorio@gmail.com.
⁶ Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, viale San Paolo 15, 00146, Rome, Italy. Electronic address: sara.terreri@opbg.net.
⁷ Department of Radiological, Oncological and Pathological Sciences, "Sapienza" University, viale del Policlinico 155, 00161, Rome, Italy. Electronic address: francesco.marampon@uniroma1.it.
⁸ Department of Clinical, Internal, Anaesthesiological and Cardiovascular Sciences, "Sapienza" University, viale del Policlinico 155, 00161, Rome, Italy. Electronic address: salvatore.minisola@uniroma1.it.
⁹ Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, IRCCS, viale San Paolo 15, 00146, Rome, Italy. Electronic address: andrea.delfattore@opbg.net.

PMID: 36526001
DOI: 10.1016/j.abb.2022.109489

Abstract

The therapeutic strategies for osteosarcoma involve both surgical approach and chemotherapy, but the identification of new therapeutic targets is particularly necessary in patients with local chemo-resistance, recurrence and lung metastases. The role of epigenetic regulation in osteosarcoma is largely unknown. Thus, in this study we disclosed the effects of histone deacetylase inhibitor drug PXD-101 on human osteosarcoma (OS) cell lines with different aggressiveness, including Saos-2, HOS and 143B cell lines. XTT assays revealed that treatment of Saos-2, HOS and 143B cells with PXD-101 decreased cell viability in a concentration-dependent manner. Fluorescence-activated cell sorting (FACS) analysis showed that PXD-101 inhibited proliferation and induced cell apoptosis. Wound healing assay indicated that PXD-101 inhibited migration of osteosarcoma cells. Real-Time RT-qPCR and protein analysis highlighted reduced expression of Runx2, Osterix and Mad2, probably due to Cyclin B1 inhibition by PXD-101 treatment. To our knowledge, this is the first study that characterized the anti-tumoral effect of PXD-101 in OS cells, suggesting a potential new therapeutic approach in osteosarcoma patients.

Keywords: Bone; Osteoblast; Osteoclast; Osteosarcoma; Therapy; Tumor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Bone Neoplasms* / genetics
Cell Line, Tumor
Cell Movement
Cell Proliferation
Epigenesis, Genetic
Histone Deacetylase Inhibitors / pharmacology
Histone Deacetylase Inhibitors / therapeutic use
Humans
Osteosarcoma* / drug therapy
Osteosarcoma* / genetics

Substances

Histone Deacetylase Inhibitors
belinostat