INACTIVATION OF CELL SURFACE RECEPTORS BY PHEOPHORBIDE a, A GREEN PIGMENT ISOLATED FROM Psychotria acuminata

Abstract

The inhibition of cytokine and monoclonal antibody binding cell surfaces caused by an extract of Psychotria acuminata, a medicinal plant used in the traditional medicine of the people of Belize (Central Africa), was attributed to the presence of pheophorbide a and pyropheophorbide a. Since the binding of tumor necrosis factor-alpha, interleukin-8, complement factor 5a as well as epidermal growth factor to target cells was dramatically reduced, the inhibition was not receptor or cytokine specific. In addition, the respective binding of radiolabeled monoclonal antibodies CL203 and R15.7 to the cell surface antigens intracellular cell adhesion molecule-1 and lymphocyte function-associated antigen-1 beta-chain was decreased by pretreatment of cells with pheophorbide a as well. In all cases, the inhibition by pheophorbides was dependent on the simultaneous presence of light, indicating causative involvement of a photodynamic process. These observations are not unique to pheophorbides and can be extended to porphyrins as well as to other photodynamic agents. Cytotoxicity resulting from photodynamic therapy (PDT) has been documented by many studies. Our investigations suggest that the inactivation of cell surface receptors contributes not only to an antitumor effect of PDT but also to the systemic immunosuppression, a serious side effect of PDT.

Influence of epidermal growth factor on photodynamic therapy of glioblastoma cells in vitro

“…This is inconsistent with the inactivation of cell surface receptors induced by a photodynamic process in other studies [7,13,42]. Moreover, our results showed that HPD alone or in association with laser irradiation increased EGF receptor expression of C6 cells.…”

Pyropheophorbide-a Methyl Ester-mediated Photosensitization Activates Transcription Factor NF-κB through the Interleukin-1 Receptor-dependent Signaling Pathway

“…Whereas the molecular mechanism by which PPME promotes IL-1 receptor internalization is unknown, it could be interesting to determine whether this effect is restricted to receptors that do not require homo-or heterodimerization for their functioning. A modification of cell-surface receptor by PPME photosensitization has recently been published (62); curiously, these authors reported that a mixture between pheorbide-a and PPME can reduce binding of cytokines to their receptors (TNF-␣, IL-8, complement factor 5a, and epidermal growth factor). As these data were obtained (i) by measuring cytokine binding to their receptor on neutrophils and (ii) with a mixture of photosensitizers, they reinforce the idea that these compounds can interact with cell-surface receptors and either inactivate them or trigger transduction pathways.…”

Isolation and characterisation of photoactive haemolytic toxin fromHeterocapsa circularisquama

“…Although, to date, little is known about the photosensitising agents present in different phytoplankton species (Oda et al 2001, Sato et al 2002, several such agents have been found in animal and plant sources (Kimura and Takahashi 1981, Glinski et al 1995, Matroule et al 1999. : Absorption spectrum of the purified haemolytic toxin and the cytotoxicity against HeLa cells at irradiances of various wavelengths.…”