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.
This study evaluated the antitumoral effect of Chloroform extract from Nitraria retusa leaves, via its major compounds β-sitosterols and palmitic acid. BALB/c mice were subcutaneously inoculated with B16-F10 cells, then treated intra-peritoneally after 7 days with the chloroform extract for 21 days. They were then euthanized, and the tumors were weighed. Lung parenchyma was analyzed. Lymphocyte and macrophages proliferation, cytotoxic T lymphocyte (CTL) activities were evaluated using the MTT assay. Macrophage phagocytosis was evaluated by measuring the lysosomal activity and nitric oxide production. Antioxidant activity was studied by cellular antioxidant activity on macrophage and splenocytes and by lipid peroxidation inhibitory activity in liver cells, kidney, and serum. β-sitosterols and palmitic acid, major compounds of chloroform extract, impeded remarkably the expansion of the transplantable tumor, protected the lung parenchyma, and increased splenocytes proliferation and both CTL activities in tumor-bearing mice. β-sitosterols and palmitic acid were also seen to have enhanced lysosomal activity of host macrophages and antioxidant cellular activity. Also, they showed an inhibitory effect of lipid peroxidation. Our results suggest that antitumoral effect of β-sitosterols and palmitic acid from chloroform extract is related with its immunomodulatory activity, and opens the way for a nutrition application and coprocessing phytotherapy against cancer.
Colorectal cancer is a malignancy with a high incidence. Currently, the drugs used in chemotherapy are often accompanied by strong side effects. Natural secondary metabolites can interfere with chemotherapeutic drugs and intensify their cytotoxic effects. This study aimed to profile the secondary metabolites from the methanol extract of Scabiosa atropurpurea and investigate their in vitro activities, alone or in combination with the chemotherapeutic agent doxorubicin. MTT assay was used to determine the cytotoxic activities. Annexin-V/PI double-staining analysis was employed to evaluate the apoptotic concentration. Multicaspase assay, quantitative reverse transcription real-time PCR (RT-qPCR), and ABC transporter activities were also performed. LC-MS analysis revealed 31 compounds including phenolic acids, flavonoids, and saponins. S. atropurpurea extract intensified doxorubicin anti-proliferative effects against resistant tumor cells and enhanced the cytotoxic effects towards Caco-2 cells after 48 h. The mRNA expression levels of Bax, caspase-3, and p21 were increased significantly whereas Bcl-2 expression level was decreased. Furthermore, the methanol extract reversed P-glycoprotein or multidrug resistance-associated protein in Caco-2 cells. In conclusion, S. atropurpurea improved chemosensitivity and modulated multidrug resistance in Caco-2 cells which makes it a good candidate for further research in order to develop a new potential cancer treatment.
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