Aim Epigallocatechin‐3‐gallate (EGCG), the major polyphenol found in green tea, exerts multiple protective effects against cardiovascular diseases, including cardiac hypertrophy. However, the molecular mechanism underlying its anti‐hypertrophic effect has not been clarified. This study revealed that EGCG could inhibit pressure overload‐induced cardiac hypertrophy by regulating the PSMB5/Nmnat2/SIRT6‐dependent signalling pathway. Methods Quantitative real‐time polymerase chain reaction and western blotting were used to determine the expression of mRNA and protein respectively. A fluorometric assay kit was used to determine the activity of SIRT6, a histone deacetylase. Luciferase reporter gene assay and electrophoretic mobility shift assay were employed to measure transcriptional activity and DNA binding activity respectively. Results EGCG could significantly increase Nmnat2 protein expression and enzyme activity in cultured neonatal rat cardiomyocytes stimulated with angiotensin II (Ang II) and heart tissues from rats subjected to abdominal aortic constriction. Nmnat2 knockdown by RNA interference attenuated the inhibitory effect of EGCG on cardiac hypertrophy. EGCG blocked NF‐κB DNA binding activity induced by Ang II, which was dependent on Nmnat2 and the subsequent SIRT6 activation. Moreover the activation of PSMB5 (20S proteasome subunit β‐5, chymotrypsin‐like) was required for EGCG‐induced Nmnat2 protein expression. Additionally, we demonstrated that EGCG might interact with PSMB5 and inhibit the activation of the proteasome. Conclusions These findings serve as the first evidence that the effect of EGCG against cardiac hypertrophy may be, at least partially, attributed to the modulation of the PSMB5/Nmnat2‐dependent signalling pathway, suggesting the therapeutic potential of EGCG in the prevention and treatment of cardiac hypertrophy.

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Background/Aim Nobiletin, a major polymethoxyflavones ( PMF s) from citri reticulatae pericarpium ( CRP ), can inhibit several forms of cancer proliferation. However, the effects of nobiletin on nasopharyngeal carcinoma ( NPC ) C666‐1 cells remain largely unknown. Materials and Methods Cell counting kit 8 ( CCK 8) assay was used to measure cell vitality. Flow cytometry was performed to measure the apoptosis rate. Quantitative real‐time polymerase chain reaction ( qRT ‐ PCR ) and Western blot analysis were applied to determine the expression of mRNA and protein, respectively. Results We showed that the proliferation rate of C666‐1 cells was inhibited and the apoptosis rate was raised after treating with nobiletin. Moreover, nobiletin inhibited the expression of poly( ADP ‐ribose)polymerase‐2 ( PARP ‐2), and the tumor suppression effect of nobiletin on C666‐1 is associated with PARP ‐2‐dependent pathway. Conclusion We demonstrated for the first time that nobiletin inhibited the growth of C666‐1 cells, which may be relative to its regulation on PARP ‐2/ SIRT 1/ AMPK signaling pathway. Our result implied that nobiletin may serve as a strategy to treat nasopharyngeal carcinoma.