A mechanism-based in vitro anticancer drug screening approach for phenolic phytochemicals.
Plant-derived phenolic compounds, including polyphenols (e.g., tannins), flavonoids, and phenolic acids, have been under investigation for their anticancer therapeutic and chemoprevention properties. Recently, certain mechanisms underlying the differential effects of green tea polyphenols (GTPPs) on tumor versus normal cells have been determined. These suggest that GTPPs may simultaneously activate multiple pathways. However, existing screening methods are insufficient for the identification of agents that possess both a cytotoxic effect on tumor cells and a protective effect on normal cells. The current study describes the establishment of an in vitro survival/apoptosis testing system based on detecting these mechanisms by a double-fluorescence method. This system is able to screen potential chemopreventive or therapeutic agents from (but not limited to) plant-derived compounds based on the pathways differentially activated by the agents. Tumor cell death and normal cell survival are detected simultaneously, in a device that co-cultures normal human cells adjacent to human tumor cells.
Hsu
Stephen
S
Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, Medical College of Georgia, Augusta, GA 30912-1126, USA. shsu@mail.mcg.edu
Yu
Fu-Xin X
FX
Huang
Qin
Q
Lewis
Jill
J
Singh
Baldev
B
Dickinson
Douglas
D
Borke
James
J
Sharawy
Mohamed
M
Wataha
John
J
Yamamoto
Tetsuya
T
Osaki
Tokio
T
Schuster
George
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D028241:Camellia sinensis / Q000737:chemistry; D002392:Catechin / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques / Q000379:methods*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D008856:Microscopy, Fluorescence / Q000379:methods; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D009369:Neoplasms / Q000473:pathology*; D010636:Phenols / Q000494:pharmacology*; D010944:Plants / Q000737:chemistry*; D059808:Polyphenols; D012016:Reference Values
D000970:Antineoplastic Agents; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D002392:Catechin