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Breast cancer is one of the malignant tumors with the highest morbidity and mortality rate. Numerous efficient anti-breast cancer drugs are being derived from the development of natural products. Voacamine (VOA), a bisindole alkaloid isolated from Voacanga africana Stapf, possesses various pharmacological and biological activities.In this study, we investigated the efficacy of VOA against breast cancer cells and elucidated the underlying mechanisms in vitro and in vivo.Human breast cancer cell line MCF-7 and mouse breast cancer cell line 4T1 were used to study the underlying anti-cancer mechanisms of VOA. The proliferation was detected by MTT, colony formation, cell proliferation and wound-healing migration assays. Flow cytometry was utilized to determine the level of reactive oxygen species (ROS) cell-cycle, apoptosis and mitochondrial membrane potential. The target proteins were analyzed by Western blot. Molecular docking was performed and scored by AutoDock. Subcutaneous cancer models in mice were established to evaluate the anticancer effects in vivo.Our results demonstrated that VOA selectively suppressed breast cancer MCF-7 and 4T1 cells proliferation with ICThese findings revealed the novel properties of VOA in promoting apoptosis of breast cancer cells by activating mitochondrial-associated apoptosis signaling pathway and inhibiting PI3K/Akt/mTOR signaling pathway and significantly decreasing tumor size without detecting appreciable toxicity. In summary, the present results demonstrated VOA could be an encouraging drug candidate to cure breast cancer, exhibiting an effective method to exploit unique drugs from natural components.

The Lower Paleozoic shale in south China has a very high maturity and experienced strong tectonic deformation. This character is quite different from the North America shale and has inhibited the shale gas evaluation and exploration in this area. The present paper reports a comprehensive investigation of maturity, reservoir properties, fluid pressure, gas content, preservation conditions, and other relevant aspects of the Lower Paleozoic shale from the Sichuan Basin and its surrounding areas. It is found that within the main maturity range (2.5 % 3.5 %) is considered a high risk for shale gas exploration. Taking the southern area of the Sichuan Basin and the southeastern area of Chongqing as examples of uplifted/folded and faulted/folded areas, respectively, geological models of shale gas content and loss were proposed. For the uplifted/folded area with a simple tectonic deformation, the shale system (with a depth > 2000 m) has largely retained overpressure during uplifting without a great loss of gas, and an industrial shale gas potential is generally possible. However, for the faulted/folded area with a strong tectonic deformation, the sealing condition of the shale system was usually destroyed to a certain degree with a great loss of free gas, which decreased the pressure coefficient and resulted in a low production capacity. It is predicted that the deeply buried shale (>3000 m) has a greater gas potential and will become the focus for further exploration and development in most of the south China region (outside the Sichuan Basin).