Abstract
Bulnesia sarmientoi (BS) has long been used as an analgesic, wound-healing and anti-inflammatory medicinal plant. The aqueous extract of its bark has been demonstrated to have anti-cancer activity. This study investigated the anti-proliferative and anti-metastatic effects of BS supercritical fluid extract (BSE) on the A549 and H661 lung cancer cell lines. The cytotoxicity on cancer cells was assessed by an MTT assay. After 72 h treatment of A549 and H661 cells, the IC50 values were 18.1 and 24.7 μg/mL, respectively. The cytotoxicity on MRC-5 normal cells was relatively lower (IC50 = 61.1 μg/mL). BSE arrested lung cancer cells at the S and G2/M growth phase. Necrosis of A549 and H661 cells was detected by flow cytometry with Annexin V-FITC/PI double staining. Moreover, the cytotoxic effect of BSE on cancer cells was significantly reverted by Nec-1 pretreatment, and BSE induced TNF-α and RIP-1 expression in the absence of caspase-8 activity. These evidences further support that BSE exhibited necroptotic effects on lung cancer cells. By wound healing and Boyden chamber assays, the inhibitory effects of BSE on the migration and invasion of lung cancer cells were elucidated. Furthermore, the chemical composition of BSE was examined by gas chromatography-mass analysis where ten constituents of BSE were identified. α-Guaiene, (−)-guaiol and β-caryophyllene are responsible for most of the cytotoxic activity of BSE against these two cancer cell lines. Since BSE possesses significant cytotoxicity and anti-metastatic activity on A549 and H661 cells, it may serve as a potential target for the treatment of lung cancer.
Highlights
Lung cancer is one of the leading causes of death in the world, responsible for more than 1.5 million deaths worldwide annually [1]
This study demonstrates that the supercritical fluid extract of Bulnesia sarmientoi (BS) (BSE) had significant cytotoxicity on A549 and H661 lung cancer cells
Under BS Supercritical fluid extraction (SFE) extract (BSE) treatment, the cell cycle arrest, necrosis by annexin V-FITC/propidium iodide (PI) double staining detection, and expressions of necroptotic proteins in cancer cells were investigated. These results indicate that BSE exhibited necroptotic effect on non-small-cell lung cancer (NSCLC) cells
Summary
Lung cancer is one of the leading causes of death in the world, responsible for more than 1.5 million deaths worldwide annually [1]. Necroptosis provides an alternative process to enhance the sensitivity of cancer cells to chemotherapeutic agents, especially for the cases where the cancer cells are resistant to apoptosis. Some plants were reported to have anti-lung cancer effects, including Podophyllum peltatum, Taxus brevifolia Nutt., Catharanthus roseus, and Camptotheca acuminata Some of their bioactive compounds had been developed as chemotherapeutic drugs, such as podophyllotoxin derivatives [17,18], taxol [19], vinca alkaloids [20] and camptothecins [21]. The aqBSE could induce apoptosis of A549 lung cancer cells via p53 induction and decrease the tumor decrease the tumor size in subcutaneous sarcoma 180 tumor-bearing nude mice [38]. The cell necroptosis induced by BSE was elucidated
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