Antiproliferative activity of guava leaf extract via inhibition of prostaglandin endoperoxide H synthase isoforms.
Prostaglandin endoperoxide H synthase (PGHS) is a key enzyme for the synthesis of prostaglandins (PGs) which play important roles in inflammation and carcinogenesis. Because the extract from Psidium guajava is known to have a variety of beneficial effects on our body including the anti-inflammatory, antioxidative and antiproliferative activities, we investigated whether the extract inhibited the catalytic activity of the two PGHS isoforms using linoleic acid as an alternative substrate. The guava leaf extract inhibited the cyclooxygenase reaction of recombinant human PGHS-1 and PGHS-2 as assessed by conversion of linoleic acid to 9- and 13-hydroxyoctadecadienoic acids (HODEs). The guava leaf extract also inhibited the PG hydroperoxidase activity of PGHS-1, which was not affected by nonsteroidal anti-inflammatory drugs (NSAIDs). Quercetin which was one of the major components not only inhibited the cyclooxygenase activity of both isoforms but also partially inhibited the PG hydroperoxidase activity. Overexpression of human PGHS-1 and PGHS-2 in the human colon carcinoma cells increased the DNA synthesis rate as compared with mock-transfected cells which did not express any isoforms. The guava leaf extract not only inhibited the PGE(2) synthesis but also suppressed the DNA synthesis rate in the PGHS-1- and PGHS-2-expressing cells to the same level as mock-transfected cells. These results demonstrate the antiproliferative activity of the guava leaf extract which is at least in part caused by inhibition of the catalytic activity of PGHS isoforms.
Kawakami
Yuki
Y
Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
Nakamura
Tomomi
T
Hosokawa
Tomoko
T
Suzuki-Yamamoto
Toshiko
T
Yamashita
Hiromi
H
Kimoto
Masumi
M
Tsuji
Hideaki
H
Yoshida
Hideki
H
Hada
Takahiko
T
Takahashi
Yoshitaka
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D019787:Linoleic Acid / Q000378:metabolism; D008041:Linoleic Acids / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry*; D031647:Psidium; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; D010936:Plant Extracts; D011994:Recombinant Proteins; C024347:9-hydroxy-10,12-octadecadienoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D019787:Linoleic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2