The hydrophilic extract from a new tomato genotype (named DHO) kills cancer cell lines through the modulation of the DNA damage response induced by Campthotecin treatment

一种新的番茄基因型的亲水提取物(名为 DHO)通过调节喜树碱治疗引起的 DNA 损伤反应来杀死癌细胞系

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作者:Daniela Barone, Carmelina Antonella Iannuzzi, Iris Maria Forte, Maria Carmen Ragosta, Maria Cuomo, Milena Dell'Aquila, Angela Altieri, Antonella Caporaso, Rosa Camerlingo, Maria Manuela Rigano, Daria Maria Monti, Amalia Barone, Paola Imbimbo, Luigi Frusciante, Marcellino Monda, Margherita D'Angelo, 

Discussion

We described the potential role of DHO extract in the modulation of DNA repair, in response to Camptothecin treatment (CPT), favoring an increased sensitivity of HeLa cell lines to topoisomerase inhibitor therapy.

Methods

Here, we used a hydrophilic extract of a new tomato genotype (named DHO) in order to modulate the Camptothecin (CPT) DNA damage response.

Results

We demonstrated increased phosphorylation of Replication Protein A 32 Serine 4/8 (RPA32 S4/8) protein in HeLa cells treated with the CPT in combination with DHO extract with respect to CPT alone. Moreover, we pointed out a change in HR intermediates resolution from Gene Conversion to Single Strand Annealing through the modified DNA repair protein RAD52 homolog (RAD52), DNA excision repair protein ERCC-1 (ERCC1) chromatin loading in response to DHO extract, and CPT co-treatment, with respect to the vehicle. Finally, we showed an increased sensitivity of HeLa cell lines to DHO extract and CPT co-treatment suggesting a possible mechanism for increasing the efficiency of cancer therapy.

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