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

Xiao-Yu Zhu1,2, Dian-Wu Guo3, Qiao-Cong Lao2

  • 1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, P. R. China.

Scientific Reports
|March 16, 2019
PubMed

Insights

Furanodiene, derived from a Chinese medicinal herb, demonstrates therapeutic and synergistic anticancer effects in zebrafish models. It also reverses drug resistance by targeting P-glycoprotein, suggesting potential for novel cancer therapies.

Area of Science:

  • Natural Products Chemistry
  • Cancer Biology
  • Pharmacology

Background:

  • Furanodiene is a natural terpenoid from Rhizoma Curcumae with known anticancer properties.
  • Zebrafish xenograft models offer a valuable platform for preclinical cancer research.
  • Understanding Furanodiene's mechanisms can lead to new cancer treatment strategies.

Purpose of the Study:

  • To evaluate Furanodiene's therapeutic efficacy in established human cancer cell line xenografts in zebrafish.
  • To investigate Furanodiene's synergistic effects with conventional chemotherapies.
  • To explore Furanodiene's potential in overcoming multidrug resistance.

Main Methods:

  • Established five human cancer cell line xenografts in zebrafish.
  • Validated models using clinically approved anticancer drugs.
  • Assessed Furanodiene's efficacy, synergy with 5-Fluorouracil, and reversal of drug resistance.
  • Investigated mechanisms including anti-angiogenesis, ROS production, DNA damage, apoptosis, and P-glycoprotein modulation.

Main Results:

  • Furanodiene showed therapeutic effects against pancreatic (JF 305) and breast (MCF-7) cancer xenografts.
  • Synergistic anticancer effects were observed with 5-Fluorouracil (5-FU) in breast (MDA-MB-231) and liver (BEL-7402) cancer models.
  • Furanodiene reversed multidrug resistance in cis-Platinum-resistant lung and Adriamycin-resistant breast cancer cells.
  • Mechanisms involved anti-angiogenesis, ROS induction, DNA breaks, apoptosis, and suppression of P-glycoprotein function and level (without affecting MDR1 expression).

Conclusions:

  • Furanodiene exhibits significant therapeutic and synergistic anticancer activities in zebrafish xenograft models.
  • Furanodiene demonstrates potential in overcoming drug resistance, possibly via P-glycoprotein inhibition.
  • These findings highlight Furanodiene as a promising candidate for further investigation in cancer therapy development.

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