Abstract
In order to harness local resources to improve well-being and human health, we aim in this study to investigate if the microalgae Dunaliella sp. isolated from the Tunisian coastal zone possesses any anticancer activity. Dunaliella sp. was cultured under normal (DSC) or stressed (DSS) conditions and extracted using different procedures. The biological activity assessment was performed on the Triple Negative Breast Cancer (TNBC) using 4T1 murine cells as a model. Results indicate that: (i) aqueous extract was the most cytotoxic compared to ethanolic and hydroalcoholic extracts; (ii) DSS activity was superior to that of DSC. DSS extracts induced apoptosis rather than necrosis, as evidenced by DNA fragmentation, PARP-1 cleavage and caspase-3 activation. Evaluation in an orthotopic TNBC model validated the anticancer activity in vivo. Intratumoral injection of DSS extract resulted in reduced tumor growth and an enhanced immune system activation. On the transcriptional side, the expression level of the immunosuppressive enzyme Arg-1 was decreased, as well as those of NOS-2 and COX-2 genes. These results suggest a potential anticancer activity of Tunisian Dunaliella sp. deserving further attention.
Highlights
Microalgae represent an important source of biologically active compounds
This study reports for the first time how an aqueous extract of an isolated strain Dunaliella sp is effective against breast cancer by inducing
The ethanolic extract used at 1 mg/mL only became cytotoxic after 48 h with 40% of dead cells compared to controls (Figure 1b)
Summary
Microalgae represent an important source of biologically active compounds. Dunaliella salina is an interesting microalga as it is characterised by its ability to produce diverse metabolites depending on the culture conditions. The type with the worst prognosis is Triple Negative Breast Cancer (TNBC), characterized by the total absence of these three receptors, which is extremely difficult to handle by either hormonal and/or targeted therapies [20] These aggressive tumors represent 12 to 17% of cases and are characterised by an elevated nuclear grade, mitotic activity and high power to metastasize to the viscera [21]. PARP-1 is composed of a 54 KDa catalytic domain, a 46 kDa DNA Binding Domain (DBD) and a 22-kD auto-modification domain (AMD) [27] It is a substrate of caspase-3 and 7, calpains, cathepsins, granzymes and matrix metalloproteases creating various exposed structural domains that subsequently induce specific forms of cell death [27]. The study combines both in vitro and in vivo experiments performed with 4T1 aggressive TNBC
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