BackgroundThe edible fruit Annona cherimola has previously shown many nutritional and medicinal properties. The current study evaluates the anti-cancer and anti-proliferative properties of Annona cherimola ethanolic leaf extract (AELE) on Acute Myeloid Leukemia (AML) cell lines cultured in vitro (Monomac-1 and KG-1).MethodsThe anti-proliferative effect of A. cherimola ethanolic leaf extract was evaluated via cell viability assay. Its pro-apoptotic effect was assessed through Cell Death ELISA and dual Annexin V/PI staining. To further investigate the molecular mechanism by which the extract promoted apoptosis and inhibited the proliferation of the AML cells used, apoptotic protein expression was determined through western blots. Extract composition was elucidated by Gas Chromatography-Mass Spectrometry (GC-MS).ResultsOur results showed that the treatment with A. cherimola ethanolic leaf extract exhibited an inhibitory effect on the proliferation of both cancer cell lines used in a dose- and time-dependent manner, with no toxic effects on normal mononuclear cells (MNCs) isolated from human bone marrow. This effect was mediated by DNA fragmentation and apoptosis, as revealed by Cell Death ELISA and dual Annexin V/PI staining. Western blot analysis revealed a Bax/Bcl2 dependent mechanism of apoptosis, as well as PARP cleavage, confirming the apoptotic results observed previously. These effects may be attributed to the presence of terpenes which constitute a large component of the leafy extract, as revealed via GC-MS.ConclusionAll the data presented in our study show that the terpene-rich A. cherimola ethanolic leaf extract exhibits an anti-proliferative and pro-apoptotic effect on the AML cell lines used.
Background Herbal medicines have been a major target for numerous studies through the past years as an alternative treatment for cancer, mainly due to their minimal effects on normal healthy cells. Annona cherimola, popularly known as Cherimoya, is an edible natural fruit rich in phytochemical components and known to possess various biological activities. Previous studies have reported the anti-cancerous effect of A. cherimola ethanolic leaf extract (AELE) on leukemia. This study aims at studying the potential anti-cancer activity of this extract in vitro in two different breast cancer cell lines, namely MDA-MB-231 and MCF-7, in addition to investigating its toxicity on normal mesenchymal stem cells. Methods The anti-proliferative effect of AELE was evaluated via cell viability assay. Propidium iodide staining, Cell Death Detection ELISA and flow cytometry analysis of Annexin V binding were used to assess cell cycle progression, DNA fragmentation and apoptosis induction, respectively. Protein expression was determined via Western Blot analysis to decipher the underlying apoptotic molecular mechanism induced upon AELE treatment. Results The anti-proliferative effect of the extract was found to be selective on the triple-negative breast cancer cell line (MDA-MB-231) in a time- and dose-dependent manner with an IC50 of 390.2 μg/mL at 48 h, with no cytotoxic effects on normal murine mesenchymal stem cells. The pro-apoptotic effect was confirmed by the increase in cellular and DNA fragmentation, flipping of the phosphatidylserine moiety to the outer leaflet, and the increase in Annexin V binding. The underlying molecular mechanism revealed the involvement of the mitochondrial pathway, as shown by alterations in mitochondrial permeability and the upregulation of cytochrome c expression. Conclusion All the data presented in our study suggest that AELE exhibits a selective anti-proliferative and pro-apoptotic effect on the chemo-resistant MDA-MB-231 breast cancer cells, providing evidence for the anti-tumor effects of A. cherimola.
Background: Sternbergia clusiana belongs to the Amaryllidaceae family and is recognized for the valuable biological activity of its major bioactive compounds. The aim of the current is to evaluate the anticancer effects of the ethanolic bulb extract of Sternbergia clusiana (ScBEE) on breast cancer cells in vitro and to further reveal the underlying cellular mechanism. Methods: An MTS cell viability assay was performed on MDA-MB-231 and MCF-7 cells, along with cell cycle analysis, cell death ELISA, Western blot analysis and an ROS production assay to decipher the mechanism of death. LC-MS/MS was also performed to identify the chemical composition of this ethanolic extract. Results: The results show a selective antiproliferative effect on both cell lines with no effect on normal mesenchymal stem cells. Further analysis suggested the activation of the apoptotic pathway as reflected by the increase in cellular and DNA fragmentation and alterations in apoptotic proteins such as Bax, Bcl-2 and c-PARP. ScBEE was also found to exhibit antioxidant effect, as shown by a decrease in ROS production. The underlying mechanism of action was explained by the presence of several bioactive compounds identified by LC-MS/MS, including alkaloids, terpenoids and phenols, which are elaborated in the manuscript. Conclusion: This study highlights the antioxidant and anticancerous properties of S.clusiana for breast cancer treatment.
Background: 1. Background: Breast Cancer is one of the most commonly diagnosed cancers worldwide and a major cause of death among women. Although chemotherapeutic agents remain the keystones in cancer therapy, significant side effects have failed to provide a safe and tolerable treatment for cancer patients. Dietary antioxidant vitamins were extensively investigated over the past years and their relevance in cancer chemotherapy remains to be elucidated. Objective: 2. Objective: In the current study, we aimed to investigate the anti-proliferative and apoptotic effects of combining γ-tocotrienol, a member of the vitamin E family, with the chemotherapeutic drug etoposide in MCF-7 and MDA-MB-231 breast cancer cell lines. Methods: 3. Methods: The antiproliferative effect of etoposide combined with γ-tocotrienol was measured using MTS viability reagent. The pro-apoptotic effect was elucidated through Cell Death ELISA and dual Annexin V/PI staining followed by flow cytometric analysis. Results: 4. Results: Our results showed that etoposide significantly decreased the cell growth of both cell lines with MDA-MB-231 cells being more sensitive to etoposide treatment than MCF-7. Moreover, the simultaneous treatment of both breast cancer cell lines with low doses of γ-tocotrienol and etoposide induced a synergistic antiproliferative effect (CI<1). Furthermore, the combination therapy significantly increased the percentage of total apoptotic cells in the MDA-MB-231 cell line and the degree of DNA fragmentation as compared to treatment with either compound alone Conclusion: 5. Conclusion: In conclusion, our results provide evidence for the profound anti-tumorigenic effect of combined etoposide and γ-tocotrienol in the breast cancer cell lines.
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