Resveratrol induces downregulation in survivin expression and apoptosis in HTLV-1-infected cell lines: a prospective agent for adult T cell leukemia chemotherapy.
Resveratrol, a phytoalexin found in grapes and wine, has been shown to exhibit a wide range of pharmacological properties and is believed to play a role in the chemoprevention of human cancer. Resveratrol has also been shown to induce antiproliferation and apoptosis of several leukemia cell lines. In the present study, we investigated the effect of resveratrol in adult T cell leukemia. Our present observations showed that resveratrol induced growth inhibition in all five human T cell lymphotrophic virus-1-infected cell lines examined, with 50% effective dose of 10.4-85.6 mM. In the resveratrol-treated cells, induction of apoptosis was confirmed by annexin V-based analyses and morphological changes. The most surprising observation was that resveratrol treatment resulted in a gradual decrease in the expression of survivin, an antiapoptotic protein, during cell apoptosis. These findings indicate that resveratrol inhibits the growth of human T cell lymphotrophic virus-1-infected cell lines, at least in part, by inducing apoptosis mediated by downregulation in survivin expression. In view of the accumulating evidence that survivin may be an important determinant of a clinical response in adult T cell leukemia, our present findings have led to the suggestion that resveratrol, a common constituent of the human diet, merits further investigation as a potential therapeutic agent for this incurable disease.
Department of Biochemistry, Nagasaki University, Nagasaki, Japan. lantisth@pop02.odn.ne.jp
Toshihisa
T
Hayashibara
Yasuaki
Y
Yamada
Susumu
S
Nakayama
Hitomi
H
Harasawa
Kazuto
K
Tsuruda
Kazuyuki
K
Sugahara
Takayuki
T
Miyanishi
Shimeru
S
Kamihira
Masao
M
Tomonaga
Tetsuo
T
Maita
D000328:Adult; D017304:Annexin A5 / Q000187:drug effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D015490:HTLV-I Infections / Q000235:genetics* / Q000517:prevention & control*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D008869:Microtubule-Associated Proteins / Q000187:drug effects* / Q000235:genetics*; D009363:Neoplasm Proteins; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D000077022:Survivin
D017304:Annexin A5; D000894:Anti-Inflammatory Agents, Non-Steroidal; C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D013267:Stilbenes; D000077022:Survivin; D000077185:Resveratrol