Abstract
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.
Highlights
Cancer is infamous as the leading cause of death in the world
Damages, and/or apoptotic process [13,14]. This emblematic polyphenol is not the only one that can act in synergy with anticancer drugs—curcumin and echistatin have previously been shown to enhance cisplatin sensitivity by modulating signaling pathways in cancer cells [15,16]. In this strategy of research for active molecules capable both of exerting a protective action against the deleterious effects of cisplatin with respect to normal cells, and of simultaneously exerting a chemosensitizing action with regard to cancer cells, we have recently focused on the potential use of a medicinal plant belonging the Ephedraceae family, Ephedra alata Decne, which has been described as decreasing the side effects of chemotherapy [17,18]
Many authors have been able to highlight the great diversity of compounds that may be present in Ephedra species, in particular, a wide variety of polyphenolic compounds, and, depending on the species, the presence of ephedrine or pseudoephedrine, which could limit their use due to the effects potentially harmful of these last two compounds
Summary
Breast cancer is the second leading cause of cancer-related deaths among women worldwide, and accounts for approximately 25% of total cancer cases and 15% of total cancer-related deaths [1]. To treat this type of cancer, there are several active modalities available, such as surgery, hormone therapy, cytotoxic therapy, radiation therapy, or a combination of these treatments [2]. Cells 2020, 9, 362 and subsequently limits its use Despite this toxicity, the use of cisplatin like taxol remain, for the moment, the only bulwark against very aggressive cancers such as breast cancer, in particular that which is diagnosed as triple negative. Triple negative breast cancers (TNBCs) represent a challenge due to the heterogeneity of the disease, and due to the absence of well-defined molecular targets [7,8], and some combinations of compounds with platinum salts could be more efficient against
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