Anti-cancer effects of methanol-ethyl acetate partitioned fraction from Magnolia grandiflora in human non-small cell lung cancer H1975 cells.

Non-small cell lung cancer (NSCLC) constitutes nearly 85% of all cases of lung cancer. Drug resistance, dose-limiting toxicity, and metastasis in NSCLC eventually reduce the efficacy of chemotherapeutics. In this study, we have shown that the methanol-ethyl acetate partitioned fraction from Magnolia grandiflora L. seeds (MEM) exhibit potential anti-cancer activities against NSCLC H1975 cells in vivo and in vitro. MEM significantly inhibited the proliferation of H1975 cells in a concentration- and time-dependent manner. Further, MEM exhibited potent anti-tumor efficacy and low toxicity in nude mice bearing H1975 tumors. Our study also showed that MEM could induce cellular apoptosis in H1975 cells by down-regulating the protein expression levels of Akt and p-Akt-473, and by increasing the ratio of Bax/Bcl-2. Also, MEM significantly inhibited metastasis-related cell invasion and migration of H1975 cells, which associated with the down-regulation of HIF-1α, MMP-2, and MMP-9 protein expression levels. Thus, our data shows that MEM may be an effective fraction of M. grandiflora in NSCLC treatment.

Miconazole triggers various forms of cell death in human breast cancer MDA-MB-231 cells.

In recent years, "drug repurposing" has become an important approach and focus of studies on anti-tumor drug research and development (R&D). As one of the first-generation broad-spectrum imidazole anti-fungal drugs, miconazole (MCZ) exhibits anti-tumor effects in addition to its anti-fungal effect. However, no report has focused on examining the effect of MCZ on the proliferation and cell-death of human breast cancer MDA-MB-231 cells. MCZ significantly inhibited the proliferation of MDA-MB-231 cells in a concentration- and time-dependent manner. We also observed that MCZ induced both apoptosis and necroptosis in MDA-MB-231 cells. Transmission electron microscopy showed submicroscopic structures in these cells, which correspond to necrotic features, in addition to the characteristic features of apoptosis. Pretreatment of cells with z-VAD-fmk, an apoptosis inhibitor or Nec-1, a necroptosis inhibitor, significantly increased their viability compared with MCZ treatment. The initial mechanism of MCZ-mediated cell death in human breast cancer MDA-MB-231 cells involves an increase in the Bax/Bcl-2 ratio, downregulation of apoptosis induced by Akt and p-Akt-473, a simultaneous upregulation of the receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like (MLKL) protein expression, and ROS production to induce necroptosis. Our results suggest that MCZ may be a potential lead compound for the development of anti-breast cancer drugs.

[Effect of methanol-ethyl acetate partitioned fractions from Descurainia sophia on proliferation and apoptosis of human non-small cell lung cancer H1975 cells].

OBJECTIVE: To investigate the effects of methanol-ethyl acetate partitioned fractions from Descurainia sophia (MEDS) on the proliferation and apoptosis of human non-small cell lung cancer H1975 cells. METHODS: The systemic solvent extraction method was used to preliminary separation of the effective fractions in the methanol extract of Descurainia sophia. The cytotoxicity of each extract (5, 10, 20, 40, and 80 µg/mL) was tested using MTT assay. Colony cloning method was used to assess the effect of different concentrations of methanol-ethyl acetate partitioned fractions from MEDS (5, 10, 20, 40, and 80 µg/ mL) on the proliferation of H1975 cells. Flow cytometric analysis with Annexin V-FITC/PI staining was performed to detect the apoptosis of the cells after treatment with different concentrations of MEDS fractions (10, 20, and 40 µg/mL). Western blotting was used to evaluate the effects of MEDS fractions on the expressions of apoptosis-related proteins Akt, Bax, and Bcl-2. The anti-tumor activity of 100 mg/kg MEDS fractions was tested in a nude mouse model bearing H1975 cell xenografts. RESULTS: MTT assay and colony forming experiment showed that MEDS fractions significantly inhibited the proliferation of H1975 cells in a dose-and time-dependent manner (P < 0.05). The results of flow cytometry showed that MEDS fractions induced obvious apoptosis of H1975 cells in a concentration-dependent manner (P < 0.05). MEDS fractions also significantly decreased the expressions of Bcl-2 and Akt protein and increased the protein expression of Bax (P < 0.05). In the tumor-bearing nude mouse model, MEDS fractions showed potent anti-tumor effects with a low toxicity to affect the body weight and organs of the mice. CONCLUSIONS: The methanol-ethyl acetate partitioned fractions from MEDS show potent anti-tumor activity both in vivo and in vitro, suggesting their value as promising therapeutic agents against lung cancer.