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Echium arenarium Guss is a Mediterranean plant traditionally used in healing skin wound and it was reported exhibiting potent antioxidant, antibacterial, and antiparasitic activities. However, antitumoral activities of this plant have not yet been explored. Here we investigated for the first time, root (EARE) and aerial part (EAAPE) extracts of E. arenarium Guss to examine cytotoxicity and apoptosis activation pathway on U266 human multiple myeloma (MM) cell line. We demonstrated that EARE and EAAPE decreased U266 cell viability in a dose dependent manner. Based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, EARE was significantly two times more efficient (IC50 value 41 μg/ml) than EAAPE (IC50 value 82 μg/ml) considering 48 h of treatment. Furthermore, after 24 h of exposure to 100 μg/ml of EARE or EAAPE, cell cycle showed remarkable increase in sub-G1 population and a decrease of U266 cells proportion in G1 phase. In addition, EARE increased cell percentage in S phase. Moreover, analysis revealed that EAAPE or EARE induced apoptosis of U266 cells after 24 h of treatment. Interestingly, depolarization of mitochondrial membrane potential and activation of caspase 3/7 were demonstrated in treated U266 cells. Phytochemical analysis of E. arenarium extracts showed that EARE exhibited the highest content of total phenolic content. Interestingly, six phenolic compounds were identified. Myricitrin was the major compound in EARE, followed by luteolin 7-O-glucoside, resorcinol, polydatin, Trans-hydroxycinnamic acid, and hyperoside. These findings proved that an intrinsic mitochondria-mediated apoptosis pathway probably mediated the apoptotic effects of E. arenarium Guss extracts on U266 cells, and this will suggest several action plans to treat MM.

Background: The lack of treatment options for patients with chemotherapy-resistant cancers is pushing the field toward the development of new therapies. 1,2,4,5-tetrazine derivatives are a class of heterocyclic compounds that exhibit a broad spectrum of antitumor activities. Objective: The purpose of this study was to assess the biological activity of four s-tetrazine derivatives by substitution of two chloride atom of 3,6-dichloro-1,2,4,5-tetrazine with long hydrophobic side chains. Methods: We analyzed the anti-proliferative effects of four s-tetrazine derivatives with MTT assay and their pro-apoptotic effect with AV/ IP flow cytometry analysis and Hoechst 33342 staining. Results: We demonstrated that 3,6-dichloro-1,2,4,5-tetrazine (compound (1)) has a cytotoxic effect and induces apoptosis. Conclusion: 3,6-dichloro-1,2,4,5-tetrazine presents a new cytotoxic drug against metastatic breast cancer cell line MDA-MB-231 in vitro.

Multiple myeloma (MM) is an incurable plasma cell malignancy with frequent patient relapse due to innate or acquired drug resistance. Cholesterol metabolism is reported to be altered in MM, therefore, we investigated the potential anti-myeloma activity of two cholesterol derivatives: the 5,6 α- and 5,6 β-epoxycholesterol (EC) isomers. To this end, viability assays were used, and isomers were shown to exhibit important anti-tumor activity in vitro in JJN3 and U266 human myeloma cell lines (HMCLs) and ex vivo in myeloma patients’ sorted CD138+ malignant cells. Moreover, we confirmed that 5,6 α-EC and 5,6 β-EC induced oxiapoptophagy through concomitant oxidative stress and caspase-3-mediated apoptosis and autophagy. Interestingly, in combination treatment a synergistic interaction was observed between 5,6 α-EC and 5,6 β-EC on myeloma cells. These data highlight a striking anti-tumor activity of 5,6 α-EC and 5,6 β-EC bioactive molecules against human myeloma cells, paving the way for their potential role in future therapeutic strategies in MM.

Introduction Despite the significant developments occurring in the treatment of cancer, multiple myeloma remains the second haematological deadly disease. The aim of this study was to investigate the antiproliferative and apoptotic activities of Olea europaea L. cv Chetoui leaf and stem extracts (OLE and OSE) on human myeloma cells, given that plant compounds provide antitumor drugs. Methods Anti-cancer activity was tested on U266 human multiple myeloma cell line using MTT and trypan blue assays. Cell cycle analysis, cell death mechanism, mitochondrial membrane potential levels and caspases activities were assessed in U266 cells using flow cytometry. The nuclear morphology of U266 cells was observed using Hoechst 33342 using fluorescent microscopy. Results Our data revealed that treatment with OLE and OSE induced anti-proliferative effects on U266 myeloma cells in dose and time dependent manner. The IC50 of OLE and OSE were 55 and 35 μg/mL, respectively after 48 h of exposure. Interestingly, cell cycle analysis showed significant decrease of U266 cells in G1 phase related to significant increase in sub-G1 population after 24 h of extract treatment. Moreover, OLE and OSE significantly induced apoptosis in U266 cell line after 24 h of treatment by inducing mitochondria dysfunctions and caspase 3/7 expression. Conclusion To our knowledge this is the first paper to be conducted on olive stem extract. Our study showed that OLE and OSE had potent anti-multiple myeloma properties. This work may form the basis for further investigation on olive extracts as potential therapeutic agent on multiple myeloma.