The butanol fraction of guava (Psidium cattleianum Sabine) leaf extract suppresses MMP-2 and MMP-9 expression and activity through the suppression of the ERK1/2 MAPK signaling pathway.
The leaf extract of guava (Psidium cattleianum Sabine) has traditionally been used for the treatment of diarrhea and diabetes in East Asia and other countries. Recently, the leaf extract has been employed in the therapy of cancer, bacterial infections, and inflammation in experimental models. However, the exact mechanisms of how guava leaf extract inhibits tumor metastasis and invasion are still unknown. In the present study, we investigated in detail the molecular mechanism(s) responsible for the potential antimetastatic and antiinvasive effects of the butanol fraction of guava leaf extract (GBF). Interestingly, we observed for the first time that GBF suppressed both matrix metalloproteinases (MMP)-9 and MMP-2 expression and activity in part through the downregulation of the ERK1/2 activation in lung cancer cells. Also, importantly, the major components of the GBF were identified as d-glucuronic acid, quercetin 3-glucuronide, loganin, and xanthyletin by LC-ESI-MS/MS. Collectively, our data indicate that the guava leaf could reduce the metastasis of lung cancer cells and therefore suggest that it could be advantageously used to control the metastatic process.
College of Oriental Medicine and Institute of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
Inhwan
I
Im
Kyung-Ran
KR
Park
Sung-Moo
SM
Kim
Chulwon
C
Kim
Jeong Ha
JH
Park
Dongwoo
D
Nam
Hyeung-Jin
HJ
Jang
Bum Sang
BS
Shim
Kyoo Seok
KS
Ahn
Ashik
A
Mosaddik
Gautam
G
Sethi
Somi K
SK
Cho
Kwang Seok
KS
Ahn
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000440:Butanols; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry*; D031647:Psidium; D012333:RNA, Messenger / Q000032:analysis; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D000440:Butanols; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9