Agave negatively regulates YAP and TAZ transcriptionally and post-translationally in osteosarcoma cell lines

Maria Ferraiuolo, Claudio Pulito, Megan Finch-Edmondson, Etleva Korita, Anna Maidecchi, Sara Donzelli, Paola Muti, Massimo Serra, Marius Sudol, Sabrina Strano, Giovanni Blandino

Research output: Contribution to journalArticle

Abstract

Osteosarcoma (OS) is the most aggressive type of primary solid tumor that develops in bone. Whilst conventional chemotherapy can improve survival rates, the outcome for patients with metastatic or recurrent OS remains poor, so novel treatment agents and strategies are required. Research into new anticancer therapies has paved the way for the utilisation of natural compounds as they are typically less expensive and less toxic compared to conventional chemotherapeutics. Previously published works indicate that Agave exhibits anticancer properties, however potential molecular mechanisms remain poorly understood. In the present study, we investigate the anticancer effects of Agave leaf extract in OS cells suggesting that Agave inhibits cell viability, colony formation, and cell migration, and can induce apoptosis in OS cell lines. Moreover, Agave sensitizes OS cells to cisplatin (CDDP) and radiation, to overcome chemo- and radio-resistance. We demonstrate that Agave extract induces a marked decrease of Yes Associated Protein (YAP) and Tafazzin (TAZ) mRNA and protein expression upon treatment. We propose an initial mechanism of action in which Agave induces YAP/TAZ protein degradation, followed by a secondary event whereby Agave inhibits YAP/TAZ transcription, effectively deregulating the Nuclear Factor kappa B (NF-κB) p65:p50 heterodimers responsible for transcriptional induction of YAP and TAZ.

Original languageEnglish
Pages (from-to)18-32
Number of pages15
JournalCancer Letters
Volume433
DOIs
Publication statusPublished - Oct 1 2018

Fingerprint

Agave
Osteosarcoma
Cell Line
Proteins
NF-kappa B
Poisons
Radio
Cisplatin
Proteolysis
Cell Movement
Cell Survival
Therapeutics
Survival Rate
Radiation
Apoptosis
Bone and Bones
Drug Therapy
Messenger RNA

Keywords

  • Agave
  • Osteosarcoma
  • Proliferation
  • Saponins
  • YAP/TAZ

Cite this

Agave negatively regulates YAP and TAZ transcriptionally and post-translationally in osteosarcoma cell lines. / Ferraiuolo, Maria; Pulito, Claudio; Finch-Edmondson, Megan; Korita, Etleva; Maidecchi, Anna; Donzelli, Sara; Muti, Paola; Serra, Massimo; Sudol, Marius; Strano, Sabrina; Blandino, Giovanni.

In: Cancer Letters, Vol. 433, 01.10.2018, p. 18-32.

Research output: Contribution to journalArticle

Ferraiuolo, M, Pulito, C, Finch-Edmondson, M, Korita, E, Maidecchi, A, Donzelli, S, Muti, P, Serra, M, Sudol, M, Strano, S & Blandino, G 2018, 'Agave negatively regulates YAP and TAZ transcriptionally and post-translationally in osteosarcoma cell lines', Cancer Letters, vol. 433, pp. 18-32. https://doi.org/10.1016/j.canlet.2018.06.021
Ferraiuolo, Maria ; Pulito, Claudio ; Finch-Edmondson, Megan ; Korita, Etleva ; Maidecchi, Anna ; Donzelli, Sara ; Muti, Paola ; Serra, Massimo ; Sudol, Marius ; Strano, Sabrina ; Blandino, Giovanni. / Agave negatively regulates YAP and TAZ transcriptionally and post-translationally in osteosarcoma cell lines. In: Cancer Letters. 2018 ; Vol. 433. pp. 18-32.
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AU - Pulito, Claudio

AU - Finch-Edmondson, Megan

AU - Korita, Etleva

AU - Maidecchi, Anna

AU - Donzelli, Sara

AU - Muti, Paola

AU - Serra, Massimo

AU - Sudol, Marius

AU - Strano, Sabrina

AU - Blandino, Giovanni

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AB - Osteosarcoma (OS) is the most aggressive type of primary solid tumor that develops in bone. Whilst conventional chemotherapy can improve survival rates, the outcome for patients with metastatic or recurrent OS remains poor, so novel treatment agents and strategies are required. Research into new anticancer therapies has paved the way for the utilisation of natural compounds as they are typically less expensive and less toxic compared to conventional chemotherapeutics. Previously published works indicate that Agave exhibits anticancer properties, however potential molecular mechanisms remain poorly understood. In the present study, we investigate the anticancer effects of Agave leaf extract in OS cells suggesting that Agave inhibits cell viability, colony formation, and cell migration, and can induce apoptosis in OS cell lines. Moreover, Agave sensitizes OS cells to cisplatin (CDDP) and radiation, to overcome chemo- and radio-resistance. We demonstrate that Agave extract induces a marked decrease of Yes Associated Protein (YAP) and Tafazzin (TAZ) mRNA and protein expression upon treatment. We propose an initial mechanism of action in which Agave induces YAP/TAZ protein degradation, followed by a secondary event whereby Agave inhibits YAP/TAZ transcription, effectively deregulating the Nuclear Factor kappa B (NF-κB) p65:p50 heterodimers responsible for transcriptional induction of YAP and TAZ.

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