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Resveratrol inhibits Extranodal NK/T cell lymphoma through activation of DNA damage response pathway
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نویسنده
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sui x. ,zhang c. ,zhou j. ,cao s. ,xu c. ,tang f. ,zhi x. ,chen b. ,wang s. ,yin l.
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منبع
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journal of experimental and clinical cancer research - 2017 - دوره : 36 - شماره : 1
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چکیده
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Background: extranodal nk/t cell lymphoma (nktcl) is a highly aggressive non-hodgkin lymphoma with poor prognosis. resveratrol (rsv,3,5,4′-trihydroxystilbene),a natural nontoxic phenolic compound found in the skin of grapes and some other spermatophytes,performs multiple bioactivities,such as antioxidant activity,anti-aging activity,reduction of cardiovascular disease risk and anticarcinogenic effect. here we report the anti-tumor effect of rsv in nktcl cell lines snt-8,snk-10 and snt-16. results: rsv inhibited nktcl cell proliferation in a dose- and time-dependent manner and arrested cell cycle at s phase. it induced nktcl cells apoptosis through mitochondrial pathway,shown as down-regulation of mcl-1 and survivin,up-regulation of bax and bad,and activation of caspase-9 and caspase-3. in addition,we found that rsv suppressed the phosphorylation level of akt and stat3,and activated dna damage response (ddr) pathway directly or through up-regulation of zta of epstein-barr virus (ebv). furthermore,using ku55933 as the inhibitor of patm,we verified that ddr played an important role in rsv inducing nktcl apoptosis. rsv also showed synergistic effect on activating ddr pathway in combination with etoposide or ionizing radiation,which resulted in cell proliferation inhibition and apoptosis. conclusions: our results provide in vitro evidence that rsv produces anti-tumor effect by activating ddr pathway in an atm/chk2/p53 dependent manner. so we suggest that rsv may be worthy for further study as an anti-tumor drug for nktcl treatment. © 2017 the author(s).
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کلیدواژه
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DNA damage response pathway; Epstein-Barr virus; Extranodal NK/T cell lymphoma; pATM; Resveratrol; Zta
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آدرس
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department of physiology and pathophysiology,school of basic medical sciences,fudan university,shanghai, China, institution of biomedical sciences,shanghai medical college,fudan university,shanghai, China, department of hematology,huashan hospital,shanghai medical college,fudan university,shanghai, China, shanghai medical college,fudan university,shanghai, China, department of pathology,zhongshan hospital,shanghai medical college,fudan university,shanghai, China, department of pathology,huashan hospital,shanghai medical college,fudan university,shanghai, China, laboratory of medical molecular biology,experimental teaching center,school of basic medical sciences,fudan university,131 dongan rd,shanghai,200032, China, department of hematology,huashan hospital,shanghai medical college,fudan university,shanghai, China, laboratory of medical molecular biology,experimental teaching center,school of basic medical sciences,fudan university,131 dongan rd,shanghai,200032, China, department of physiology and pathophysiology,school of basic medical sciences,fudan university,shanghai,china,laboratory of medical molecular biology,experimental teaching center,school of basic medical sciences,fudan university,131 dongan rd,shanghai,200032, China
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Authors
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