Abstract 7303: The algal carotenoid diatoxanthin shows anti-cancer and cardio-protective properties: RNA seq analysis of potential targets

Abstract

Abstract Introduction: Natural bioactive pigments are of great interest for human health. Marine organisms are underexplored as source of useful metabolites. Diatoms produce diatoxantin (diatox), a xanthophyll with several properties (chemo-preventive, anti-inflammatory, antioxidant, photoprotective, immunomodulatory), that may have beneficial effects. Doxorubicin (doxo) is still one of the most effective chemotherapeutic drugs used in breast cancer (BC) treatment, but has side effects, particularly cardiotoxicity, mainly due to oxidative stress and cardiomyocyte damage. We have assessed the anti-cancer effects of diato, also verifying the absence of cardiotoxicity. Experimental procedures: Diatox was administered to MDA-MB-231 triple negative BC (TNBC) in vitro, in combination with doxo by MTT and by 3D-spheroid assays. The modulation of diatox on the secretome of both TNBC cells and Human Umbilical-Vein Endothelial cell line (HUVEc) was assessed in vitro by angiogenesis arrays. Gene expression analysis was evaluated by measuring different inflammation and angiogenesis gene expression in cells treated with diato, by qPCR; while transcriptomic analysis was performed by RNA-Seq to verify diato effects on pathways involved in TNBC progression and in HUVEc inflammation. Results: Diatox showed an inhibitory effect on the proliferation of MDA-MB-231 cells and, in combination with doxo, was able to inhibit TNBC spheroid growth, reducing their 3D-integrity and decreasing their viability. Diatoxx was able to down-regulate genes involved in inflammatory and angiogenic processes in HUVEc stimulated by TNFα (angiostatin, IL2, IL4 and PECAM-1 in antibody array and TGFβ1, TGFβ2, TIMP1 and TIMP2 gene in qPCR analysis). Moreover, diatox reduced several biological processes involved in inflammation and tumour development and metastasis, as demonstrated by RNA-Seq data. In TNBC cells diatox down-regulated ANGPT1, GPR37, ANG, QRICH2, MUC1 genes involved in angiogenesis processes, while EPHA7 was up-regulated. In TNFα-stimulated HUVEc, diatox down-regulated angiogenin, a powerful inducer of angiogenesis, and HSPA12A and EDNRB, which are involved in the regulation of macrophage cytokine production. Conclusions: Diatox shows to be a promising chemo-preventive and angiopreventive natural compound in cancer prevention and therapy. Microalgae derived drugs can represent a potential and relevant source of novel nutraceutical and preventive substances, which can be considered as supplements in therapeutic strategies for cancer prevention. Acknowledgements: The studies were supported by Stazione Zoologica Anton Dohrn, by "Antitumor Drugs and Vaccines from the Sea "ADViSE" project (PG/2018/0494374). Citation Format: Douglas M. Noonan, Luana Calabrone, Luigi Pistelli, Christophe Brunet, Clementina Sansone, Danilo Morelli, Giovanna Chiorino, Francesca Guana, Adriana Albini. The algal carotenoid diatoxanthin shows anti-cancer and cardio-protective properties: RNA seq analysis of potential targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7303.