Abstract

Aim of study: 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). Materials and methods: 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. Results: 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-G₁ 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. © 2009 Elsevier Ireland Ltd. All rights reserved.

Author keywords

Apoptosis; Caspase; LLC; MAPK; Solanum lyratum herba

Indexed keywords

EMTREE drug terms: 4',6 diamidino 2 phenylindole; adenosine diphosphate ribose; carboplatin; caspase; caspase 3; caspase 8; caspase 9; DNA nucleotidylexotransferase; hexane; mitogen activated protein kinase; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; plant extract; Solanum lyratum extract; solvent; stress activated protein kinase; unclassified drug

EMTREE medical terms: animal cell; animal experiment; animal model; antineoplastic activity; apoptosis; article; cell cycle G1 phase; chromatin condensation; controlled study; DNA fragmentation; down regulation; enzyme activation; enzyme phosphorylation; female; flow cytometry; immunohistochemistry; in vitro study; in vivo study; Lewis carcinoma; lung cancer; mouse; nick end labeling; nonhuman; protein expression; regulatory mechanism; tumor growth; Western blotting

MeSH: Animals; Apoptosis; Blotting, Western; Caspases; Cell Line; Flow Cytometry; Fluorescent Dyes; In Situ Nick-End Labeling; MAP Kinase Signaling System; Mice; Plant Extracts; Solanum
Medline is the source for the MeSH terms of this document.

Species Index: Solanum lyratum

Chemicals and CAS Registry Numbers: 4',6 diamidino 2 phenylindole, 47165-04-8; DNA nucleotidylexotransferase, 9027-67-2; adenosine diphosphate ribose, 20762-30-5; carboplatin, 41575-94-4; caspase, 186322-81-6; caspase 3, 169592-56-7; caspase 9, 180189-96-2; hexane, 110-54-3; mitogen activated protein kinase, 142243-02-5; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase, 58319-92-9; stress activated protein kinase, 155215-87-5;Caspases, 3.4.22.-; Fluorescent Dyes; Plant Extracts