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?3-Adrenoreceptor Activity Limits Apigenin Efficacy in Ewing Sarcoma Cells: A Dual Approach to Prevent Cell Survival.

ABSTRACT: Ewing Sarcoma (ES) is an aggressive paediatric tumour where oxidative stress and antioxidants play a central role in cancer therapy response. Inhibiting antioxidants expression, while at the same time elevating intracellular reactive oxygen species (ROS) levels, have been proposed as a valid strategy to overcome ES cancer progression. Flavonoid intake can affect free radical and nutritional status in children receiving cancer treatment, but it is not clear if it can arrest cancer progression. In particular, apigenin may enhance the effect of cytotoxic chemotherapy by inducing cell growth arrest, apoptosis, and by altering the redox state of the cells. Little is known about the use of apigenin in paediatric cancer. Recently, ?3-adrenergic receptor (?3-AR) antagonism has been proposed as a possible strategy in cancer therapy for its ability to induce apoptosis by increasing intracellular levels of ROS. In this study we show that apigenin induces cell death in ES cells by modulating apoptosis, but not increasing ROS content. Since ES cells are susceptible to an increased oxidative stress to reduce cell viability, here we demonstrate that administration of ?3-ARs antagonist, SR59230A, improves the apigenin effect on cell death, identifying ?3-AR as a potential discriminating factor that could address the use of apigenin in ES.

SUBMITTER: Pasha A

PROVIDER: S-EPMC6540192 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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β3-Adrenoreceptor Activity Limits Apigenin Efficacy in Ewing Sarcoma Cells: A Dual Approach to Prevent Cell Survival.

Pasha Amada A Vignoli Marina M Subbiani Angela A Nocentini Alessio A Selleri Silvia S Gratteri Paola P Dabraio Annalisa A Casini Tommaso T Filippi Luca L Fotzi Ilaria I Favre Claudio C Calvani Maura M

International journal of molecular sciences 20190430 9

Ewing Sarcoma (ES) is an aggressive paediatric tumour where oxidative stress and antioxidants play a central role in cancer therapy response. Inhibiting antioxidants expression, while at the same time elevating intracellular reactive oxygen species (ROS) levels, have been proposed as a valid strategy to overcome ES cancer progression. Flavonoid intake can affect free radical and nutritional status in children receiving cancer treatment, but it is not clear if it can arrest cancer progression. In ...[more]

PMID: 31052299

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Project description:AimLung metastases are a negative prognostic factor in Ewing sarcoma, however, the incidence and significance of sub-centimetre pulmonary nodules at diagnosis is unclear. The aims of this study were to (1): determine the incidence of indeterminate pulmonary nodules (IPNs) in patients diagnosed with Ewing sarcoma (2); establish the impact of IPNs on overall and metastasis-free survival and (3) identify patient, oncological and radiological factors that correlate with poorer prognosis in patients that present with IPNs on their staging chest CT.Materials & methodsBetween 2008 and 2016, 173 patients with a first presentation of Ewing sarcoma of bone were retrospectively identified from an institutional database. Staging and follow-up chest CTs for all patients with IPN were reviewed by a senior radiologist. Clinical and radiologic course were examined to determine overall- and metastasis-free survival for IPN patients and to identify demographic, oncological or nodule-specific features that predict which IPN represent true lung metastases.ResultsFollowing radiologic re-review, IPN were found in 8.7% of patients. Overall survival for IPN patients was comparable to those with a normal staging chest CT (2-year overall survival of 73.3% [95% CI 43.6-89] and 89.4% [95% CI 81.6-94], respectively; p = 0.34) and was significantly better than for patients with clear metastases (46.0% [95% CI 31.9-59]; p < 0.0001). Similarly, there was no difference in metastasis-free survival between 'No Metastases' and 'IPN' patients (p = 0.16). Lung metastases developed in 40% of IPN patients at a median 9.6 months. Reduction of nodule size on neoadjuvant chemotherapy was associated with worse overall survival in IPN patients (p = 0.0084).ConclusionIPN are not uncommon in patients diagnosed with Ewing sarcoma. In this study, we were unable to detect a difference in overall- or metastasis-free survival between patients with IPN at diagnosis and patients with normal staging chest CTs.

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?3-Adrenoreceptor Activity Limits Apigenin Efficacy in Ewing Sarcoma Cells: A Dual Approach to Prevent Cell Survival.

Publications

β3-Adrenoreceptor Activity Limits Apigenin Efficacy in Ewing Sarcoma Cells: A Dual Approach to Prevent Cell Survival.

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