Sensitization and synergistic anti-cancer effects of Furanodiene identified in zebrafish models

  • Sci Rep. 2019 Mar 14;9(1):4541. doi: 10.1038/s41598-019-40866-2.
Xiao-Yu Zhu  1  2 ,  Dian-Wu Guo  3 ,  Qiao-Cong Lao  2 ,  Yi-Qiao Xu  2 ,  Zhao-Ke Meng  3 ,  Bo Xia  2 ,  Hua Yang  1 ,  Chun-Qi Li  4 ,  Ping Li  5
Affiliations
  • 1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, P. R. China.
  • 2. Hunter Biotechnology, Inc, F1A, building 5, No. 88 Jiangling Road, Binjiang Zone, Hangzhou City, Zhejiang Province, 310051, P. R. China.
  • 3. Minsheng Biopharma Research Institute, F8, building F, No. 1378 Wenyixi Road, Yuhang Zone, Hangzhou City, Zhejiang Province, 310011, P. R. China.
  • 4. Hunter Biotechnology, Inc, F1A, building 5, No. 88 Jiangling Road, Binjiang Zone, Hangzhou City, Zhejiang Province, 310051, P. R. China. [email protected].
  • 5. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, P. R. China. [email protected].
PMID: 30872660 DOI: 10.1038/s41598-019-40866-2
Abstract

Furanodiene is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents Anticancer effects in various types of Cancer cell lines. In this study, we have successfully established zebrafish xenografts with 5 various human Cancer cell lines; and validated these models with anti-cancer drugs used clinically for treating human Cancer patients. We found that Furanodiene was therapeutically effective for human JF 305 pancreatic Cancer cells and MCF-7 breast Cancer cells xenotranplanted into zebrafish. Furanodiene showed a markedly synergistic anti-cancer effect when used in combination with 5-FU (5-Fluorouracil) for both human breast Cancer MDA-MB-231 cells and human liver Cancer BEL-7402 cells xenotransplanted into zebrafish. Unexpectedly, Furanodiene reversed multiple drug resistance in the zebrafish xenotransplanted with cis-Platinum-resistant human non-small cell lung Cancer cells and Adriamycin-resistant human breast Cancer cells. Furanodiene played its anti-cancer effects through anti-angiogenesis and inducing ROS production, DNA strand breaks and Apoptosis. Furanodiene suppresseed efflux transporter Pgp (P-glycoprotein) function and reduced Pgp protein level, but no effect on Pgp related gene (MDR1) expression. These results suggest sensitizition and synergistic anti-cancer effects of Furanodiene that is worthy of a further investigation.

Products