Pyrogallol structure in polyphenols is involved in apoptosis-induction on HEK293T and K562 cells.
As multiple mechanisms account for polyphenol-induced cytotoxicity, the development of structure-activity relationships (SARs) may facilitate research on cancer therapy. We studied SARs of representatives of 10 polyphenol structural types: (+)-catechin (1), (-)-epicatechin (2), (-)-epigallocatechin (3), (-)-epigallocatechin gallate (4), gallic acid (5), procyanidin B2 (6), procyanidin B3 (7), procyanidin B4 (8), procyanidin C1 (9), and procyanidin C2 (10). Amongst them, the polyphenols containing a pyrogallol moiety (3-5) showed the most potent cytotoxicic activity. These compounds evoked a typical DNA-laddering phenomenon in HEK293T, which indicated that the induction of apoptosis at least partly mediates their cytotoxic activity. Anti-oxidative capacity of compounds 3-5 were comparable to those of the trimers 9 and 10, which were not cytotoxic. Therefore, we suggest that pyrogallol moiety is important for fitting of polyphenols to their putative target molecule(s) in non-oxidative mechanism.
Mitsuhashi
Shinya
S
Division of Applied Bioscience, Research Faculty of Agriculture, Hokkaido University, Kita-9, Nishi-9, Kita-ku, Sapporo 060-8589, Japan.
Saito
Akiko
A
Nakajima
Noriyuki
N
Shima
Hiroshi
H
Ubukata
Makoto
M
D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D011748:Pyrogallol / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000975:Antioxidants; D011748:Pyrogallol