A New Highlight of Ephedra alata Decne Properties as Potential Adjuvant in Combination with Cisplatin to Induce Cell Death of 4T1 Breast Cancer Cells In Vitro and In Vivo.

Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially for some anticancer drugs such as cisplatin, which induces a nephrotoxicity. In the strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin and exerting a chemosensitizing action with regard to cancer cells, we tested the potential effects of Ephedra alata Decne extract (E.A.) rich in polyphenolic compounds towards a 4T1 breast cancer model in vitro and in vivo. We showed that E.A. extract inhibited cell viability of 4T1 breast cancer cells and induced apoptosis in a caspase-dependent manner, which involved intrinsic pathways. Very interestingly, we observed a synergic antiproliferative and pro-apoptotic action with cisplatin. These events were associated with a strong decrease of breast tumor growth in mice treated with an E.A./cisplatin combination and simultaneously with a decrease of hepato- and nephrotoxicities of cisplatin.

Study of Potential Anti-Inflammatory Effects of Red Wine Extract and Resveratrol through a Modulation of Interleukin-1-Beta in Macrophages.

Inflammation has been described as an initiator event of major diseases with significant impacts in terms of public health including in cardiovascular disease, autoimmune disorders, eye diseases, age-related diseases, and the occurrence of cancers. A preventive action to reduce the key processes leading to inflammation could be an advantageous approach to reducing these associated pathologies. Many studies have reported the value of polyphenols such as resveratrol in counteracting pro-inflammatory cytokines. We have previously shown the potential of red wine extract (RWE) and the value of its qualitative and quantitative polyphenolic composition to prevent the carcinogenesis process. In this study, we addressed a new effect of RWE in inflammation through a modulation of IL-1ß secretion and the NLRP3 inflammasome pathway. NLRP3 inflammasome requires two signals, priming to increase the synthesis of NLRP3 and pro-IL-1ß proteins and activation, which activates NLRP3. Inflammasome formation is triggered by a range of substances such as lipopolysaccharide (LPS). Using two different macrophages, one of which does not express the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), which is essential to form active inflammasome complexes that produce IL-1ß, we show that RWE decreases IL-1 ß secretion and gene expression whatever line is used. Moreover, this strong reduction of pro-inflammatory IL-1ß is associated with a decrease of NLRP3 and, in J774A, ASC protein expression, which depends on the choice of activator ATP or nigericin.