Abstract
Arctium lappa is a well-known traditional medicinal plant in China (TCM) and Europe that has been used for thousands of years to treat arthritis, baldness or cancer. The plant produces lignans as secondary metabolites which have a wide range of bioactivities. Yet, their ability to reverse multidrug resistance (MDR) in cancer cells has not been explored. In this study, we isolated six lignans from A. lappa seeds, namely arctigenin, matairesinol, arctiin, (iso)lappaol A, lappaol C, and lappaol F. The MDR reversal potential of the isolated lignans and the underlying mechanism of action were studied using two MDR cancer cell lines, CaCo2 and CEM/ADR 5000 which overexpress P-gp and other ABC transporters. In two-drug combinations of lignans with the cytotoxic doxorubicin, all lignans exhibited synergistic effects in CaCo2 cells and matairesinol, arctiin, lappaol C and lappaol F display synergistic activity in CEM/ADR 5000 cells. Additionally, in three-drug combinations of lignans with the saponin digitonin and doxorubicin MDR reversal activity was even stronger enhanced. The lignans can increase the retention of the P-gp substrate rhodamine 123 in CEM/ADR 5000 cells, indicating that lignans can inhibit the activity of P-gp. Our stud...Continue Reading
References
Jun 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·G FiskumA L Lehninger
Jan 1, 1994·Cold Spring Harbor Symposia on Quantitative Biology·M M GottesmanI Pastan
Mar 1, 1994·International Journal of Cancer. Journal International Du Cancer·C MullerG Laurent
Oct 8, 1998·FEBS Letters·R IshisakaK Utsumi
May 20, 1999·Annual Review of Pharmacology and Toxicology·S V AmbudkarM M Gottesman
Jun 18, 2002·Blood Cells, Molecules & Diseases·Thomas EfferthRoss Davey
Aug 9, 2002·Biochemical Pharmacology·Songyot AnuchapreedaPorn-ngarm Limtrakul
Jan 8, 2003·The Journal of Cell Biology·Jean-Ehrland RicciDouglas R Green
Aug 5, 2003·Journal of Cancer Research and Clinical Oncology·B HausottB Marian
Aug 26, 2004·The Annals of Pharmacotherapy·Monica A SummersJames W McAuley
Jan 18, 2006·Cancer Letters·S MajumderS K Choudhuri
Feb 3, 2006·Cancer Research·Suresh AwaleHiroyasu Esumi
Sep 14, 2006·Pharmacological Reviews·Ting-Chao Chou
Jan 22, 2008·Cancer Chemotherapy and Pharmacology·Tomohiro NabekuraShuji Kitagawa
Dec 17, 2008·Current Drug Metabolism·Michael Wink
Sep 29, 2009·European Journal of Pharmacology·Mahmoud Zaki El-ReadiMichael Wink
Nov 26, 2009·Oncogene·E PeuhuJ E Eriksson
May 25, 2011·Journal of Cellular Biochemistry·Xiangyang YaoZhimin Yin
Apr 27, 2012·Frontiers in Microbiology·Michael WinkMahmoud Zaki El-Readi
Oct 16, 2012·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Safaa Yehia EidMichael Wink
Nov 14, 2012·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Safaa Yehia EidMichael Wink
Nov 14, 2013·Molecular Cancer Therapeutics·Qing SunYing Huang
Jan 8, 2014·Journal of Biochemical and Molecular Toxicology·Huan-qin WangJing Wang
Citations
Mar 3, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hanmei LiMichael Wink
Jan 30, 2016·Oncotarget·Gang ChenXu Wang
Jun 16, 2016·Oncotarget·Subburayan KarthikeyanHarsha Vasudev Hegde
May 11, 2017·Frontiers in Pharmacology·María L GonzálezMaría C Carpinella
Mar 30, 2017·Experimental and Therapeutic Medicine·Hefei HuangZhiyong Zhou
Aug 23, 2020·Medicines·Donovan A McGrowderJabari Brown
Sep 8, 2015·Medicines·Michael Wink
Jun 4, 2018·Chinese Journal of Integrative Medicine·Huan-Dong ZhaoYu-Xiang Chen
Jul 25, 2019·Frontiers in Plant Science·Dongdong WangAtanas G Atanasov
Jul 9, 2020·Frontiers in Pharmacology·Boshra TinoushMichael Wink
Mar 7, 2020·European Journal of Pharmacology·Heng ChenJun Peng
May 20, 2021·Pharmaceutical Biology·Xiao LiRui-Yi Yang
Jan 18, 2018·Chemical Reviews·Zhuohua SunKatalin Barta
Dec 29, 2017·Journal of Agricultural and Food Chemistry·Lujia LiYan Xie
Oct 14, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J WeiY Ding