ABSTRACT
BACKGROUND: Longikaurin A is a natural ent-kaurene diterpenoid isolated from Isodon genus. The ent-kaurene diterpenoids isolated from medicinal plants have been shown to have anti-disease effects. The present study was designed to examine the anti-tumour effects of longikaurin A (LK-A) in nasopharyngeal carcinoma in vitro and in vivo. METHODS: Apoptosis and cell cycle arrest were determined by flow cytometry analysis of the cells treated with Longikaurin A. The proteins of apoptosis signaling pathway were detected by western blotting analysis. Finally, we examined whether LK-A exhibits anti-tumour activity in xenograft models. RESULTS: Longikaurin A inhibited the cell growth by inducing apoptosis and cell cycle arrest. At low concentrations, longikaurin A induced S phase arrest and at higher concentrations, longikaurin A induced caspase-dependent apoptosis by regulating apoptotic molecules. Finally, longikaurin A significantly inhibited the tumour growth of CNE2 xenografts in vivo and showed no obvious effect on the body weights of the mice. CONCLUSION: Our results suggest that Longikaurin A exhibited anti-tumour activity in nasopharyngeal carcinoma in vitro and in vivo.
Subject(s)
Antineoplastic Agents/therapeutic use , Diterpenes, Kaurane/therapeutic use , Nasopharyngeal Neoplasms/drug therapy , Amino Acid Chloromethyl Ketones/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Carcinoma , Caspase 3/metabolism , Caspase 9/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Diterpenes, Kaurane/chemistry , Diterpenes, Kaurane/pharmacology , Mice , Mice, Nude , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/enzymology , Nasopharyngeal Neoplasms/pathology , Poly(ADP-ribose) Polymerases/metabolism , S Phase/drug effects , Signal Transduction/drug effects , Tumor Stem Cell Assay , Up-Regulation/drug effects , Xenograft Model Antitumor AssaysABSTRACT
Cancer stem cells (CSCs) are a small proportion of tumor cells that may be responsible for tumor metastasis and recurrence. Our recent research indicated that longikaurin A (LK-A) exhibited anti-tumor activity in nasopharyngeal carcinoma (NPC) both in vitro and in vivo. Here, we further investigated whether LK-A could suppress the stemness of NPC cells. Sphere formation assay was used to assess the self-renewal ability of the cells treated with LK-A. Side population (SP) was determined by flow cytometry to measure the influence of LK-A on NPC SPs. The expression of the c-myc and fibronectin was detected by western blotting. The cytotoxicity of LK-A in combination with cisplatin to NPC cells was determined by MTT assay. Colony formation assay was used to verify whether LK-A could sensitize NPC cells to radiation and reverse the radiotherapy resistance. In the present study, we found that LK-A reduced the number and size of spheroid formation and decreased the SP cell percentage of the S18 cell line at a low concentration. Furthermore, LK-A treatment downregulated the expression of c-myc and fibronectin in NPC cell lines. Moreover, LK-A could significantly enhance the chemotherapeutic and radiotherapeutic sensitivity of NPC cell lines and reverse acquired radiotherapy resistance of Sune2-IR. Our data revealed that LK-A could suppress the stemness of NPC cells and may enhance the efficacy of radiotherapy and chemotherapy.