Mutagenicity and tumor-promoting effects of Tiglium seed extract via PKC and MAPK signaling pathways.
Tiglium seed is a seed of mature Croton Tiglium Linne containing croton oils, which have been traditionally used as laxative or purgative. As it contains phorbol derivatives, we investigated the mutagenicity and tumor-promoting activity of Tiglium seed. Tiglium seed extract produced the mutagenic responses in five Salmonella typhimurium strains in Ames assay, whereas it did not alter the frequencies of chromosomal aberrations or micronuclei, indicating that it exerted the mutagenic potential, not clastogenicity. Accompanied with phosphorylation of connexin43 (Cx43) and extracellular signal-regulated kinases 1/2 (ERK1/2), Tiglium seed extract inhibited gap junctional intercellular communication (GJIC) associated with tumor-promoting potential. Importantly, these effects were blocked by a protein kinase C (PKC) inhibitor or mitogen-activated protein kinase (MAPKs) inhibitors, suggesting that Tiglium seed-induced GJIC inhibition was regulated by phosphorylation of Cx43 via PKC and MAPKs signaling. In conclusion, Tiglium seed has mutagenicity, possibly linking to tumor-promoting potential through the dysfunction of GJIC.
a Graduate School of Translational Medicine , Seoul National University College of Medicine , Seoul , Republic of Korea.
Ji-Young
JY
Kim
Jun-Won
JW
Yun
Yun-Soon
YS
Kim
Euna
E
Kwon
Hyung Jun
HJ
Choi
Su-Cheong
SC
Yeom
Byeong-Cheol
BC
Kang
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D002869:Chromosome Aberrations / Q000187:drug effects; D018031:Connexin 43 / Q000378:metabolism; D029802:Croton / Q000737:chemistry*; D017629:Gap Junctions / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009153:Mutagens / Q000633:toxicity; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000633:toxicity*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D012639:Seeds / Q000737:chemistry*
D002273:Carcinogens; D018031:Connexin 43; D009153:Mutagens; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases
Tiglium seed; gap junctional intercellular communication; mitogen-activated protein kinases; mutagenicity; protein kinase C