Inactivation of cell surface receptors by pheophorbide a, a green pigment isolated from Psychotria acuminata.
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.
Glinski
J A
JA
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
David
E
E
Warren
T C
TC
Hansen
G
G
Leonard
S F
SF
Pitner
P
P
Pav
S
S
Arvigo
R
R
Balick
M J
MJ
Panta
E
E
D001531:Belize; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000494:pharmacology; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017319:Photosensitizing Agents / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D011166:Porphyrins / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D016209:Interleukin-8; D017319:Photosensitizing Agents; D011166:Porphyrins; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D002734:Chlorophyll; D015936:Complement C5a; C032623:pheophorbide a