AIM Emerging studies have shown that application of low concentration of bioactive phytomolecules can confer anti-proliferative effects on tumour cells by inducing senescence pathways. The alkaloid berberine is recognized for its anti-cancer attributes but its potential to induce senescence in tumour cells is least understood. MATERIALS AND METHODS The present work assessed the mechanisms pertaining to dose-dependent anti-proliferative effects of berberine in the perspective of senescence and inflammation using human non-small cell lung cancer cell line (A549). KEY FINDINGS Amongst the different tested bioactive phytomolecules, berberine treatment suppressed the proliferation of A549 cells regardless of the concentration applied. Application of low doses of berberine induced a weak SA-β-gal activity and p21WAF1 expression but did not show evidence of SASP activation due to absence of NF-κB activation and expression of proinflammatory genes. However, treatment with higher dose of berberine showed no evidence of SA-β-gal activity or p21WAF1 expression, but instead induced apoptosis and suppressed the expression of cell cyclins. The proliferative capacity of berberine treated cells was at par with control cells and no SA-β-gal activity could be observed in first generation of berberine treated cells. mTOR pathway showed no distinct activation on account of berberine treatment thereby further emphasizing that low dose of berberine induced quiescence and not senescence in A549 cells. SIGNIFICANCE Taken together, our observations indicate that despite its strong anti-proliferative effects, low dose berberine treatment may only induce transient changes akin to quiescence that needs to be considered before implying pro-senescence attributes of berberine in cancer therapeutics.

中文翻译：

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小ber碱通过调节细胞周期蛋白和独立于mTOR途径的炎症诱导A549癌细胞的剂量依赖性静止和凋亡。

目的新兴研究表明，低浓度生物活性植物分子的应用可通过诱导衰老途径对肿瘤细胞产生抗增殖作用。生物碱小ka碱因其抗癌特性而被公认，但其在肿瘤细胞中诱导衰老的潜力却鲜为人知。材料和方法本研究从衰老和炎症的角度出发，使用人非小细胞肺癌细胞系（A549）评估了与小ber碱剂量依赖性抗增殖作用有关的机制。主要发现在测试的不同生物活性植物分子中，小applied碱处理抑制了A549细胞的增殖，而与所施加的浓度无关。小剂量小ber碱的施用诱导了弱的SA-β-gal活性和p21WAF1表达，但由于缺乏NF-κB激活和促炎基因的表达而未显示SASP激活的证据。然而，高剂量的小ber碱治疗未显示SA-β-gal活性或p21WAF1表达的证据，而是诱导了细胞凋亡并抑制了细胞周期蛋白的表达。小碱处理的细胞的增殖能力与对照细胞相当，在第一代小ber碱处理的细胞中未观察到SA-β-gal活性。由于使用小ber碱处理，mTOR途径未显示出明显的激活，因此进一步强调了低剂量的小ber碱在A549细胞中诱导的是静止而不是衰老。意义综上所述，