The antiproliferative effect of lectin from the edible mushroom (Agaricus bisporus) on human keratinocytes: preliminary studies on its use in psoriasis.
Lectins or agglutinins are proteins with affinity for specific sugar residues. Peanut agglutinin (PNA) and the lectin from the edible mushroom (Agaricus bisporus, ABL) both bind to the disaccharide galactosyl beta-1,3-N-acetyl galactosamine alpha-. This is expressed in keratinocytes as an O-linked chain on CD44, a polymorphic membrane glycoprotein. Many lectins are mitogens and PNA is a mitogen for colonic epithelial cells. However, ABL reversibly inhibits proliferation of colonic cancer cell lines without cytotoxicity and thus has therapeutic potential in situations such as psoriasis where proliferation is increased. We have therefore investigated the effect of ABL on the growth of normal human cultured keratinocytes and a human papilloma virus (HPV)-transformed cell line. In a 5-day dose-response study, keratinocyte growth was greatly reduced by 1.0 microg/mL ABL and completely inhibited by 3.0 microg/mL ABL (ANOVA, P < 0.0001). Exposure to 1.0 microg/mL ABL for only 8 h gave the same growth inhibition as did continued exposure for 3 days. No cytotoxic or morphological changes were observed. An HPV-immortalized cell line was relatively resistant to ABL: in a 5-day dose-response study, exposure to 30 microg/mL was required to inhibit cell growth completely. Topical application of ABL 0.01% or 0.1% to normal human skin caused no change in skin erythema, blood flow or thickness compared with vehicle or baseline (n = 6). ABL 0. 1% in white soft paraffin was compared with vehicle in 11 psoriatic patients, using comparative contralateral plaques. Twice daily application for 2 weeks showed no significant difference from vehicle-treated sites, although the skin thickness of plaques fell from 5.3 +/- 0.4 (n = 11, mean +/- SEM) to 4.1 +/- 0.3 mm. In view of the in vitro results further studies are warranted, particularly if means can be found to improve the epidermal penetration of the relatively large ABL molecule (60 kDa).
Parslew
R
R
University Department of Dermatology, University of Liverpool, UK.
Jones
K T
KT
Rhodes
J M
JM
Sharpe
G R
GR
D000328:Adult; D000364:Agaricus / Q000737:chemistry*; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology*; D037102:Lectins / Q000494:pharmacology*; D008875:Middle Aged; D011565:Psoriasis / Q000473:pathology*; D012867:Skin / Q000187:drug effects
C041433:Agaricus lectins; D037102:Lectins