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De Novo Generation of Somatic Stem Cells by YAP/TAZ
Published on: May 7, 2018
Agave negatively regulates YAP and TAZ transcriptionally and post-translationally in osteosarcoma cell lines
Maria Ferraiuolo1, Claudio Pulito1, Megan Finch-Edmondson2
1Oncogenomic and Epigenetic Unit, Molecular Chemoprevention Group, Department of Research, Diagnosis and Innovative Technologies, Translational Research Area, Regina Elena National Cancer Institute, Rome, Italy.
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.
Insights
Agave leaf extract shows promise as a novel cancer therapy for osteosarcoma (OS). It inhibits cancer cell growth, migration, and induces cell death, while also sensitizing cells to conventional treatments.
Area of Science:
- Oncology
- Natural Product Chemistry
- Molecular Biology
Background:
- Osteosarcoma (OS) is a highly aggressive bone cancer with poor outcomes for metastatic or recurrent cases.
- Novel, less toxic anticancer agents are needed, and natural compounds like Agave are being explored.
- The molecular mechanisms underlying Agave's anticancer properties are not well understood.
Purpose of the Study:
- To investigate the anticancer effects of Agave leaf extract on osteosarcoma cells.
- To elucidate the molecular mechanisms of Agave's action in osteosarcoma.
- To evaluate Agave's potential to overcome chemo- and radio-resistance in osteosarcoma.
Main Methods:
- Treatment of osteosarcoma cell lines with Agave leaf extract.
- Assessment of cell viability, colony formation, and cell migration.
- Analysis of apoptosis induction and sensitization to cisplatin (CDDP) and radiation.
- Quantification of Yes Associated Protein (YAP) and Tafazzin (TAZ) mRNA and protein expression.
- Investigation of the Nuclear Factor kappa B (NF-κB) pathway.
Main Results:
- Agave leaf extract significantly inhibited osteosarcoma cell viability, colony formation, and migration.
- Agave extract induced apoptosis in osteosarcoma cell lines.
- Agave sensitized osteosarcoma cells to cisplatin and radiation, overcoming resistance.
- Agave treatment markedly decreased YAP and TAZ mRNA and protein expression.
- Agave was shown to induce YAP/TAZ protein degradation and inhibit their transcription via NF-κB deregulation.
Conclusions:
- Agave leaf extract demonstrates significant anticancer activity against osteosarcoma.
- Agave acts by downregulating YAP/TAZ expression and potentially overcoming therapeutic resistance.
- Agave represents a promising natural compound for developing new osteosarcoma treatment strategies.
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