Caspase and mitogen activated protein kinase pathways are involved in Solanum lyratum herba induced apoptosis

• Published in: Journal of ethnopharmacology 2009-05, Vol.123 (1), p.121-127
• Main Authors: Lee, Jin-Hyuk, Lee, Yun-Hee, Lee, Hyo-Jung, Lee, Hyo-Jeong, Lee, Eun-Ok, Ahn, Kwang Seok, Shim, Bum Sang, Bae, Hyunsu, Choi, Seung-Hoon, Ahn, Kyoo-Seok, Baek, Nam-In, Kim, Dae-Keun, Kim, Sung-Hoon
• Format: Article
• Language: English
• Subjects: Animals; anticarcinogenic activity; Apoptosis; Apoptosis - drug effects; biochemical pathways; Biological and medical sciences; Blotting, Western; carcinoma; Caspase; Caspases - metabolism; Cell Line; chemoprevention; chromatin; cultured cells; cytotoxicity; DNA fragmentation; ethnobotany; Flow Cytometry; Fluorescent Dyes; General pharmacology; immunohistochemistry; In Situ Nick-End Labeling; in vitro studies; LLC; MAP Kinase Signaling System; MAPK; mechanism of action; Medical sciences; medicinal plants; medicinal properties; Mice; neoplasms; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Extracts - pharmacology; protein kinases; Solanum; Solanum - chemistry; Solanum lyratum; Solanum lyratum herba
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2009.02.013

Solanum lyratum herba (SLH) has been traditionally used for the treatment of febrifuge, diarrhea, eye disease and cancer with little scientific evidences. Thus, in the present study, to elucidate the antitumor mechanism of SLH: in vitro and in vivo experiments were performed with hexane fraction of Solanum lyratum herba (HSLH). Cytotoxicity assay, 4′-6-diamidino-2-phenylindole (DAPI) staining, flow cytometric analysis for sub-G1 peaks, Western blot analysis were used with the antibodies of apoptosis related proteins in vitro. In addition, the effect of HSLH on in vivo tumor growth was evaluated in Lewis lung carcinoma (LLC) tumor model and immunohistochemistry also was performed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in tumor section. HSLH exhibited cytotoxicity against LLC cells most effectively among its solvent fractions. Ladder like DNA fragmentation and apoptotic features such as chromatin condensation and apoptotic bodies were observed in HSLH treated LLC cells by 4′-6-diamidino-2-phenylindole staining. HSLH also significantly increased sub-G 1 peaks, activated caspase-8, -9 and -3 proteins and cleaved poly(ADP-ribose) polymerase (PARP). Furthermore, HSLH increased the phosphorylation of extracellular signal-regulated kinase (ERK), transiently activated phospho-JNK (c- jun N-terminal kinase) and downregulated phospho-p38 MAPK. In addition, we have found for the first time HSLH treatment effectively suppressed the in vivo growth of LLC to up to ∼30% of untreated control at 50 mg/kg and significantly increased apoptotic expression in tumor section by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Taken together, these findings strongly demonstrate that hexane fraction of Solanum lyratum herba exerts antitumor activity via caspase activation and MAPK regulation and can be effectively applied to lung cancer as a cancer chemopreventive agent.