title: H9 Inhibits Tumor Growth and Induces Apoptosis via Intrinsic and Extrinsic Signaling Pathway in Human Non-Small Cell Lung Cancer Xenografts.
abstract: H9, a novel herbal extract, demonstrated cytotoxicity in A549 non-small cell lung cancer (NSCLC) cell lines. In this study, we investigated whether H9, and/or co-treatment with an anticancer drug, pemetrexed (PEM), inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. The mice were separated into groups and administered H9 and PEM for 2 weeks. Protein and mRNA levels were detected using western blotting and reverse transcription polymerase chain reaction, respectively; immunohistochemistry (IHC) was also performed on the tumor tissues. H9 and co-treatment with PEM induced the cleavage of proapoptotic factors, such as caspase-3, caspase-8, caspase-9, and poly(ADP)-ribose polymerase (PARP). Expression levels of cell-death receptors involving Fas/FasL, TNF-related apoptosisinducing ligands (TRAIL), and TRAIL receptors were increased by H9 and co-treatment with PEM. Furthermore, analysis of levels of cell-cycle modulating proteins indicated that tumor cells were arrested in the G1/S phase. In addition, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt survival signaling pathways were inhibited by H9 and co-treatment with PEM. In conclusion, H9 and co-treatment with PEM inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. These results indicate that H9 and co-treatment with PEM can be used as an anticancer therapy in NSCLC.
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Min-Je
authors: MJ
authors: Kim
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Sae-Bom
authors: SB
authors: Kwon
authors: Department of Laboratory Animal Medicine, Veterinary Science Research Institute, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Seung Hoon
authors: SH
authors: Ham
authors: Department of Laboratory Animal Medicine, Veterinary Science Research Institute, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Eui-Suk
authors: ES
authors: Jeong
authors: Department of Laboratory Animal Medicine, Veterinary Science Research Institute, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Yang-Kyu
authors: YK
authors: Choi
authors: Graduate School of Future Convergence Technology, Genomic Informatics Center, Hankyong National University, Anseong 456-749, Republic of Korea.
authors: Kang Duk
authors: KD
authors: Choi
authors: College of Pharmacy, Chungbuk Nation University, Chungbuk 361-763, Republic of Korea.
authors: Jin Tae
authors: JT
authors: Hong
authors: Oriental Medical Hospital, Dongguk University, Ilsan 780-714, Republic of Korea.
authors: Seung Hyun
authors: SH
authors: Jung
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Do-Young
authors: DY
authors: Yoon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts