Piper nigrum ethanolic extract rich in piperamides causes ROS overproduction, oxidative damage in DNA leading to cell cycle arrest and apoptosis in cancer cells

详细信息    查看全文

• 作者：Valdel&uacute ; cia Maria Alves de Souza Grinevicius^a ; Maicon Roberto Kviecinski^b ; N&aacute ; dia Sandrini Ramos Santos Mota^a ; Fabiana Ourique^a ; Luiza Sheyla Evenni Porfirio Will Castro^a ; Rafaela Rafognato Andreguetti^a ; Joã ; o Francisco Gomes Correia^a ; Danilo Wilhem Filho^c ; Claus Trö ; ger Pich^d ; Rozangela Curi Pedrosa^a ; ^{rozangela.pedrosa@ufsc.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Doxorubicin (PubChem CID ; 31703) ; Piperine (PubChem CID ; 638024) ; Piperyline (PubChem CID ; 636537)
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：2 August 2016
• 年：2016
• 卷：189
• 期：Complete
• 页码：139-147
• 全文大小：1205 K

文摘

Ayurvedic and Chinese traditional medicine and tribal people use herbal preparations containing Piper nigrum fruits for the treatment of many health disorders like inflammation, fever, asthma and cancer. In Brazil, traditional maroon culture associates the spice Piper nigrum to health recovery and inflammation attenuation.

c_2">Aims of the study

The aim of the current work was to evaluate the relationship between reactive oxygen species (ROS) overproduction, DNA fragmentation, cell cycle arrest and apoptosis induced by Piper nigrum ethanolic extract and its antitumor activity.

c_3">Methods

The plant was macerated in ethanol. Extract constitution was assessed by TLC, UV–vis and ESI-IT-MS/MS spectrometry. The cytotoxicity, proliferation and intracellular ROS generation was evaluated in MCF-7 cells. DNA damage effects were evaluated through intercalation into CT-DNA, plasmid DNA cleavage and oxidative damage in CT-DNA. Tumor growth inhibition, survival time increase, apoptosis, cell cycle arrest and oxidative stress were assessed in Ehrlich ascites carcinoma-bearing mice.

c_4">Results

Extraction yielded 64 mg/g (36% piperine and 4.2% piperyline). Treatments caused DNA damage and reduced cell viability (EC₅₀=27.1±2.0 and 80.5±6.6 µg/ml in MCF-7 and HT-29 cells, respectively), inhibiting cell proliferation by 57% and increased ROS generation in MCF-7 cells (65%). Ehrlich carcinoma was inhibited by the extract, which caused reduction of tumor growth (60%), elevated survival time (76%), cell cycle arrest and induced apoptosis. The treatment with extract increased Bax and p53 and inhibited Bcl-x_L and cyclin A expression. It also induced an oxidative stress in vivo verified as enhanced lipid peroxidation and carbonyl proteins content and increased activities of glutathione reductase, superoxide dismutase and catalase. GSH concentration was decreased in tumor tissue from mice.

c_5">Conclusion

The ethanolic extract has cytotoxic and antiproliferative effect on MCF-7 cells and antitumor effect in vivo probably due to ROS overproduction that induced oxidative stress affecting key proteins involved in cell cycle arrest at G1/S and triggering apoptosis. Finally, the overall data from this study are well in line with the traditional claims for the antitumor effect of Piper nigrum fruits.