Induction of natural killer activity by xanthenone analogues of flavone acetic acid: relation with antitumour activity.
Flavone-8-acetic acid (FAA) induces haemorrhagic necrosis and tumour regression in experimental tumours and induces natural killer (NK) activity. Xanthenone-4-acetic acid (XAA) forms the basis of a series of analogues of FAA which vary in antitumour potency. FAA, XAA and 15 XAA derivatives were tested for their ability to induce either NK activity in mouse spleens or haemorrhagic necrosis in mouse colon 38 tumours. Some derivatives were active in both assays (one at a dose 8-fold lower than that of FAA). When both assays were quantitated, a significant correlation (r = 0.85; P less than 0.001) was found. NK assays could be useful in screening compounds such as FAA and XAA analogues which appear to mediate their antitumour activity by biological response modification. Since tumour necrosis may not be mediated directly by NK cells, FAA and active XAA derivatives may exert pleiotropic effects that include NK induction and tumour necrosis by acting on host cells to release cytokines.
Ching
L M
LM
Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
Joseph
W R
WR
Zhuang
L
L
Atwell
G J
GJ
Rewcastle
G W
GW
Denny
W A
WA
Baguley
B C
BC
D000818:Animals; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D007155:Immunologic Factors / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D014966:Xanthenes / Q000494:pharmacology* / Q000627:therapeutic use
D007155:Immunologic Factors; D014966:Xanthenes; C066138:xanthenone-4-acetic acid