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.
Highlights
In recent years, the anti-cancer potential of natural products from medicinal plants, especially those used in traditional Chinese medicine, has been gradually recognized by the scientific community[1,2,3,4,5]
To confirm whether response of zebrafish xenografts to cancer drugs is similar to the response of mammalian model systems, we treated the xenotransplanted zebrafish with each of 10 known anti-cancer drugs (Bevacizumab, cis-Platinum, Endostar, Paclitaxel, Vinorelbine, Adriamycin, 5-FU, Hydroxyurea, Irinotecan and Gemcitabine) and Furanodiene for 48 h
Xenotransplanted zebrafish were generated by microinjection of approximately 800 human cancer cells labeled with CM-Dil into the yolk sac of zebrafish that were at 48 hpf as we reported previously[34]
Summary
The anti-cancer potential of natural products from medicinal plants, especially those used in traditional Chinese medicine, has been gradually recognized by the scientific community[1,2,3,4,5]. After a 48 h treatment, Bevacizumab, cis-Platinum, Endostar, Paclitaxel, Vinorelbine, Adriamycin, 5-FU, Hydroxyurea, Irinotecan and Gemcitabine all significantly inhibit tumor growth in the zebrafish xenotransplanted with various types of human cancer cells (Fig. 1).
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