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Reversible Inhibition of Proliferation of Epithelial Cell Lines by Agaricus bisporus (Edible Mushroom) Lectin¹

Departments of Medicine [L. Y., J. D. M., J. M. R.] and Biochemistry [D. G. F., J. A. S.], University of Liverpool, P. O. Box 147, Liverpool L69 3BX, United Kingdom

² To whom requests for reprints should be addressed, at the Department of Medicine, University of Liverpool, P. O. Box 147, Liverpool, L69 3BX United Kingdom.

Galactosyl β-1,3-N-acetyl galactosamine (Gal β-1,3-GalNAc) (Thomsen Friedenreich antigen), the Class I core sequence in O-linked oligosaccharide chains, behaves as an oncofetal antigen showing increased expression in many epithelial malignancies. Previous work has shown that peanut agglutinin (PNA), a lectin that binds Gal β-1,3-GalNAc, stimulates proliferation in HT-29 (human colon cancer) cells and normal human colonic epithelium and this implies that cell surface glycoproteins which express Gal β-1,3-GalNAc may play an important role in the regulation of epithelial cell proliferation. We have now studied the effect on epithelial cells of another dietary Gal β-1,3-GalNAc-binding lectin, the edible mushroom Agaricus bisporus lectin (ABL). This differs from PNA in its ability to bind also to sialylated Gal β-1,3-GalNAc.

In contrast to PNA, ABL (25 µg/ml) inhibited incorporation of [³H]-thymidine into DNA of HT29 colon cancer cells by 87% (95% confidence limit, 85–89%), Caco-2 colon cancer cells by 16% (95% confidence limit, 12–20%), MCF-7 breast cancer cells by 50% (95% confidence limit, 47–52%), and Rama-27 rat mammary fibroblasts by 55% (95% confidence limit, 51–60%) when these cells were grown for 24 h in serum-free medium. When assessed by cell count, similar inhibition of proliferation of HT29 cells by ABL was found. In the presence of 2% fetal calf serum (which contains the ABL-binding glycoprotein fetuin), the inhibitory effect of ABL on cell proliferation was still demonstrable but at increased ABL concentration (60 µg/ml for 49% inhibition). Ten µg/ml ABL completely abolished the stimulatory effect on [³H]thymidine incorporation of epidermal growth factor (100 pg/ml) and PNA (25 µg/ml) and markedly inhibited the stimulatory effect of insulin (50 ng/ml).

ABL (0.2 mg/ml) caused no cytotoxicity to HT29, MCF-7, and Rama-27 cells as measured by trypan blue exclusion, and inhibition of proliferation in HT29 cells caused by 50 µg/ml ABL was reversible after removal of the lectin. Binding studies with ¹²⁵I-labeled ABL suggested a single class of binding site with an apparent K_d value of (4.12 ± 0.29) x 10^–7 M with (3.6 ± 0.3) x 10⁷ binding sites/cell.

A. bisporus lectin is a reversible noncytotoxic inhibitor of epithelial cell proliferation which deserves study as a potential agent for cancer therapy.

¹ This work was supported by a bursary to L. Y. from the Commission of the European Community.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 5/18/93. Accepted 7/27/93.

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