Andrographolide potentiates the antitumor effect of topotecan in acute myeloid leukemia cells through an intrinsic apoptotic pathway

Abstract

BackgroundTopotecan (TP) is an anticancer drug acting as topoisomerase I inhibitor that is used in the treatment of many types of cancers including leukemia, but it has significant side effects. Andrographolide, a compound extracted from Andrographis paniculata, was recently proven to inhibit the growth of cancer cells and can induce apoptosis. The aim of this study is to investigate the possible synergism between TP and andrographolide in acute myeloid cells in vitro.Materials and methodsU937 acute myeloid leukemic cells were cultured using Roswell Park Memorial Institute (RPMI) medium and then treated for 24 h with TP and andrographolide prepared through the dilution of dimethyl sulfoxide (DMSO) stocks with RPMI on the day of treatment. Cell proliferation was assessed using cell proliferation assay upon treatment with both compounds separately and in combination. Cell-cycle study and apoptosis detection were performed by staining the cells with propidium iodide (PI) stain and Annexin V/PI stain, respectively, followed by flow cytometry analysis. Western blotting was used to assess the expression of various proteins involved in apoptotic pathways.ResultsBoth TP and andrographolide showed an antiproliferative effect in a dose-dependent manner when applied on U937 cells separately; however, pretreating the cells with andrographolide before applying TP exhibited a synergistic effect with lower inhibitory concentrations (half-maximal inhibitory concentration). Treating the cells with TP alone led to specific cell-cycle arrest at S phase that was more prominent upon pretreatment combination with andrographolide. Using Annexin V/PI staining to assess the proapoptotic effect following the pretreatment combination showed an increase in the number of apoptotic cells, which was supported by the Western blot results that manifested an upregulation of several proapoptotic proteins expression.ConclusionThe pretreatment of U937 with andrographolide followed by low doses of TP showed an enhancement in inducing apoptosis when compared to the application of each compound separately.

Enhanced cellular uptake and photochemotherapeutic potential of a lipophilic strained Ru(ii) polypyridyl complex

“…61 Many signaling pathways are involved, including p53-mediated activation of pro-apoptotic factors as a result of DNA double-stranded breaks, MAP-kinase activation, and the capacity for DNA repair. [62][63][64] It was previously demonstrated that Ru(II) anticancer drugs can trigger DNA damage which in turn activates apoptosis via the intrinsic pathway. 65 Zhang and coworkers reported the intercalative potential of Ru(II) polypyridyl complexes which were shown to induce apoptosis in A549 cells, as concluded from ow cytometric studies.…”

Beta-Tocotrienol Exhibits More Cytotoxic Effects than Gamma-Tocotrienol on Breast Cancer Cells by Promoting Apoptosis via a P53-Independent PI3-Kinase Dependent Pathway

“…MDA-MB-231 cells were seeded into 6 well plates at a density of 10 5 cells/mL. Cells, except the controls, were treated with 10, 20, and 30 µM of beta-tocotrienol after a 24 h incubation period (37 • C in a humidified atmosphere containing 5% CO2), After the desired period of treatment (24 h), the cellular proteins were extracted using Q-proteome Mammalian Protein kit (QIAGEN) as previously described [52]. Proteins were quantified using Lowry assay.…”

Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis

“…Currently, combinations of chemotherapeutic drugs constitute the backbone of AML treatment, with a wide spectrum of different side effects, starting with anemia, hair loss, and diarrhea, in addition to nervous and fertility problems later [3]. Over the years, the serious adverse effects of chemotherapy treatment have stimulated researchers to divert their focus towards natural compounds that may be effective in treating various malignancies, including leukemia, with lower toxicity [4][5][6][7].…”