Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune 411038, Maharashtra, India.
Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune 411038, Maharashtra, India.
Bioorg Chem. 2021 May;110:104776. doi: 10.1016/j.bioorg.2021.104776. Epub 2021 Feb 24.
Cancer stem cells (CSCs) are involved in recurrent hepatocellular carcinoma (HCC), yet there is a lack of effective treatment that targets these CSCs. CD44+ and CD133+ CSCs are markedly expressed in HepG2 cells and were isolated and characterized using fluorescence-activated cell sorting (FACS) analysis. Since piperine is known as an effective molecule against metastasis, we thought to investigate the effect of piperine against CD44+/CD133+ CSCs. Herein, piperine was found to be active against these CSCs. Also, it was found appropriate to respite at the 'subG/G and G/G' phase of the cell cycle analysis, respectively. TGF-β activated epithelial-mesenchymal transition (EMT) has been involved in the invasion and metastasis of HepG2 cells in hepatocellular carcinoma. Therefore, we next investigated the effect of piperine on different biomarkers that remarkably takes part in the process of EMT using flow cytometric analysis. Piperine was found able to repress the epithelial marker (E-cadherin) but was unable to restore the level of Vimentin (mesenchymal marker) and SNAIL (EMT-inducing transcription factor). Therefore, the findings of this study revealed that piperine could be an effective treatment strategy for recurrent hepatocarcinogenesis.
癌症干细胞（CSCs）参与复发性肝细胞癌（HCC），但缺乏针对这些 CSCs 的有效治疗方法。CD44+和 CD133+CSCs 在 HepG2 细胞中明显表达，并通过荧光激活细胞分选（FACS）分析进行分离和鉴定。由于胡椒碱是一种有效的抗转移分子，我们认为研究胡椒碱对 CD44+/CD133+CSCs 的作用。结果发现胡椒碱对这些 CSCs 具有活性。此外，在细胞周期分析中，它分别在“subG/G 和 G/G”阶段得到适当缓解。TGF-β激活的上皮-间充质转化（EMT）已参与肝癌中 HepG2 细胞的侵袭和转移。因此，我们接下来使用流式细胞术分析研究了胡椒碱对 EMT 过程中显著参与的不同生物标志物的影响。结果发现胡椒碱能够抑制上皮标志物（E-钙黏蛋白），但不能恢复间充质标志物（波形蛋白）和 EMT 诱导转录因子（Snail）的水平。因此，本研究结果表明，胡椒碱可能是复发性肝癌发生的有效治疗策略。
