alisol-b-monoacetate and Lung-Neoplasms

Tumor microenvironment has attracted more and more attention in oncology. Alisol B23 acetate (AB23A) inhibits the proliferation of tumor cells including non-small cell lung cancer (NSCLC) cells. However, whether AB23A plays a role in the tumor microenvironment of NSCLC still remains obscure.. After THP-1 cells were polarized to M0 type by PMA, M0 macrophages were differentiated into M1 by LPS and IFNγ, and were differentiated into M2 by IL-4 and IL-13. The differentiation of THP-1 cells was detected by flow cytometry. After AB23A was given to macrophage RT-qPCR and ELISA detected the expressions of IL-6, IL-1β, IL-10 and TGF-β. Western blot and RT-qPCR detected the expressions of CD11b and CD18 at both mRNA and protein levels. Lung cancer cell A549 cells were induced by above related macrophage culture medium. Cell proliferation was detected by CCK-8. Tunel, wound healing and Transwell detected the apoptotic, migration and invasion capabilities. Next, M0 and M1-type macrophages were cultured in the cell culture medium of conventional A549 cells, to which AB23A was added. Subsequently, cell differentiation and inflammatory response were measured. Finally, the expression of CD18 in A549 cells was knocked down to construct NSCLC tumor-bearing mice and AB23A was applied for intragastric administration. Immunohistochemistry detected the polarization of macrophages in tumor tissues. Western blot detected the expressions of CD11b, CD18, invasion-, migration- and apoptosis-related proteins.. AB23A promoted the polarization of macrophages towards M1, thus promoting the apoptosis and inhibiting the invasion and migration of A549 cells. The tumor cell culture medium induced M0 macrophages to M2, while AB23A reversed this effect. AB23A targeted CD11b/CD18 and improved the polarization of macrophages, thereby affecting tumor invasion, migration and apoptosis.. AB23A affected the polarization of tumor-associated macrophages through the targeted regulation of CD11b/CD18, thus inhibiting the development of lung cancer.

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Cholestenones; Interleukin-10; Interleukin-13; Interleukin-4; Interleukin-6; Lung Neoplasms; Macrophages; Mice; RNA, Messenger; Transforming Growth Factor beta; Tumor Microenvironment

The aim of the present study was to investigate the effects of alisol B 23‑acetate (AB23A) on inhibiting the viability and inducing apoptosis of human non‑small cell lung cancer (NSCLC) cells and the anticancer mechanisms of AB23A in vitro. The viability of A549 cells following treatment with different doses of AB23A was examined using a Cell Counting Kit‑8 assay. Subsequently, apoptosis and the cell cycle were detected using flow cytometric analysis. The effect of AB23A on migration and invasion of A549 cells was detected by wound healing and Transwell assays. Western blotting was performed to determine the relative expression of Bax/Bcl‑2, phosphatidylinositol 3‑kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR). AB23A markedly inhibited the viability enhanced apoptosis of A549 cells and arrested the cell cycle in G1 phase. Additionally, AB23A upregulated the ratio of Bax/Bcl‑2 in the A549 cells in a concentration‑dependent manner. The results of wound healing and Transwell assays indicated that AB23A also suppresses the migration and invasion ability of A549 cells. Furthermore, AB23A reduced the protein levels of phosphorylated AKT, PI3K and mTOR. In conclusion, AB23A exerted anti‑cancer activity via inhibiting cells viability, migration and invasion, and promoting apoptosis. Therefore, AB23A is a potential antitumor drug for the treatment of NSCLC.

Topics: A549 Cells; Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line; Cell Movement; Cell Survival; Cholestenones; Humans; Lung Neoplasms; Neoplasm Invasiveness; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases

Alisol B-23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale, has been reported to exert anti-proliferative activities in human colon, ovarian and gastric cancer cells. However, the anti-cancer effect of this compound on human lung cancer cells has not yet been thoroughly elucidated. In the present study, we investigated the effects of AB23A on the cell viability and apoptosis in human lung cancer A549 and NCI-H292 cells. The results indicated that AB23A inhibited the growth of A549 and NCI-H292 cells in dose- and time-dependent manner, however, there was only weak cytotoxicity on normal bronchial epithelial cells. The induction of apoptosis by AB23A was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed that AB23A decreased mitochondrial membrane potential (MMP) and up regulated reactive oxygen species (ROS) level. Meanwhile, the increased Bax/Bcl-2 ratio, activated caspase-3, caspase-9 and PARP were observed. In addition, AB23A increased the release of cytochrome c from mitochondria and the translocation of apoptotic inducing factor (AIF) into nuclei. Taken together, these results indicated that AB23A induced apoptosis by activating the intrinsic pathway, and suggested that AB23A can be used as a potential modulating agent in lung cancer.

Topics: Alisma; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Proliferation; Cholestenones; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Lung Neoplasms; Mitochondria; Molecular Conformation; Structure-Activity Relationship; Tumor Cells, Cultured