title: Trichosanthes kirilowii fruits inhibit non-small cell lung cancer cell growth through mitotic cell-cycle arrest.
abstract: Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer cases and the reported overall 5-year survival rate is less than 5%. Natural medicines have attracted much attention due to their lower toxicity and fewer side effects. Trichosanthes kirilowii Maxim (TKM) fruits are commonly used in cancer treatment in combination with other Chinese medicinal herbs. However, little is known about their biological functions and mechanisms in NSCLC cells. In this study, we investigated the efficacy of TKM fruits in NSCLC cells using cell proliferation, invasion, migration, and anchorage independent assays and a Xenograft NSCLC tumor model, and explored the possible biological mechanism by flow cytometric analysis, cDNA microarray and real-time PCR. Results showed that TKM fruits significantly suppressed NSCLC cell proliferation, migration, invasion, tumorigenicity and tumor growth, and significantly extended the survival time of NSCLC-bearing mice. Flow cytometric analysis showed that TKM fruits significantly induced G2-M arrest, necrosis and apoptosis in NSCLC cells. cDNA microarray analysis revealed that TKM fruits regulated the differential expression of 544 genes, and the differential expression of selected genes was also confirmed. Gene ontology (GO) analysis showed that 18 of first 20 biological processes were involved in cell cycle and mitosis. These results indicate that TKM fruits have certain inhibitory effect on NSCLC cells through cell-cycle and mitosis arrest, and suggest that TKM fruits may be an important resource for developing new antitumor drugs, and a potent natural product for treating patients with NSCLC.
authors.affiliation: Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai 200071, P. R. China , Laboratory of Integrative Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P. R. China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Ni
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zhu
authors.forename: Chenyuan
authors.initials: C
authors.lastname: Gong
authors.forename: Yinbin
authors.initials: Y
authors.lastname: Luo
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.forename: Wuxiong
authors.initials: W
authors.lastname: Zhou
authors.forename: Shiguo
authors.initials: S
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008938:Mitosis / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D029778:Trichosanthes / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts
keywords: Cell Cycle; Lung Cancer; Microarray; Mitosis; Natural Medicine; Trichosanthes kirilowii Maxim Fruits