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. 2018 Sep;17(3):755-761.
doi: 10.1177/1534735417740631. Epub 2017 Nov 20.

Evaluation Fucoidan Extracts From Undaria pinnatifida and Fucus vesiculosus in Combination With Anticancer Drugs in Human Cancer Orthotopic Mouse Models

Maryam Burney  1 , Lata Mathew  1 , Anjali Gaikwad  1 , Elizabeth K Nugent  1   2 , Anneliese O Gonzalez  1   2 , Judith A Smith  1   2   3
Affiliations

Evaluation Fucoidan Extracts From Undaria pinnatifida and Fucus vesiculosus in Combination With Anticancer Drugs in Human Cancer Orthotopic Mouse Models

Maryam Burney et al. Integr Cancer Ther. 2018 Sep.

Abstract

Objective: To determine the activity of fucoidan from Undaria pinnatifida (UPF) and Fucus vesiculosus (FVF) when given in combination of chemotherapy drugs using selected human breast or ovarian cancer orthotopic mouse models.

Methods: Mice were inoculated with 1 × 106 cells of TOV-112d, MCF-7, or ZR-75 subcutaneously or SKOV3-GFP-Luc intraperitoneally on day 0. MCF-7 and ZR-75 mice were administered with estradiol valerate 2 mg/kg in 0.2 mL castor oil subcutaneously two days prior to cell inoculation. Mice were randomized to one of six arms (N = 10/arm) paclitaxel, UPF/paclitaxel, FVF/paclitaxel, tamoxifen, UPF/tamoxifen, or FVF/tamoxifen. Tumors were measured three times per week for 28 days.

Results: Improved activity was observed with UPF or FVF in combination with tamoxifen in both the MCF-7 and ZR-75D breast cancer mouse models. Decreased activity of paclitaxel was observed when given in combination with UPF or FVF in both breast cancer mouse models. The combination of FVF/tamoxifen in the TOV-112d ovarian cancer mouse model had improved activity but no there was difference observed with the UPF/tamoxifen in either ovarian cancer mouse model. No difference was observed with combination of UPF or FVF with paclitaxel in human ovarian cancer SKOV3 or TOV-112d orthotopic mouse models.

Conclusion: This study did confirm that UPF/FVF in combination with tamoxifen did not decrease tamoxifen activity in both breast and ovarian cancer, with some potential to improve activity compared to tamoxifen alone in breast cancers. Previous in vitro studies had suggested UPF and FVF had overall synergistic activity with paclitaxel; however, in the current in vivo human cancer mouse model studies there was no change in paclitaxel activity when given in combination with UPF or FVF in either of the two human ovarian cancer models. Furthermore, this study demonstrated that UPF or FVF given in combination with paclitaxel had a potential antagonistic effect in breast cancer models. Additional studies are warranted to delineate mechanisms contributing to variation in the in vivo activity when given in combination with paclitaxel. As a first step, a clinical pharmacokinetic study evaluating impact of FVF/UPF given in combination with chemotherapy in patients with solid tumors is underway.

Keywords: Fucus vesiculosus; Undaria pinnatifida; fucoidans; paclitaxel; tamoxifen.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JAS has received unrestricted research grant from Marinova associated with funding current research and future clinical study. MB, AG, LM, EKN and AOG have nothing to declare.

Figures

Figure 1.
Figure 1.
(a) Summary of the combination of fucoidans in combination with paclitaxel in SKOV3-GPF-Luc human ovarian cancer orthotopic model. No significant change in tumor growth was seen. (b) Summary of the combination of fucoidans in combination with tamoxifen in SKOV3-GPF-Luc human ovarian cancer orthotopic model. There was no significant change in tumor growth.
Figure 2.
Figure 2.
(a) Summary of the combination of the fucoidans in combination with paclitaxel in TOV-112d human ovarian cancer orthotopic model. No significant change in tumor growth was seen. (b) Summary of the combination of the fucoidans in combination with tamoxifen in TOV-112d human breast cancer orthotopic model. There was statistically significant change in tumor growth with FVF/tamoxifen.
Figure 3.
Figure 3.
(a) Summary of the combination of the fucoidans in combination with paclitaxel in MCF-7 human breast cancer orthotopic model. There was statistically significant change in tumor growth with FVF/paclitaxel and UPF/paclitaxel. (b). Summary of the combination of the fucoidans in combination with tamoxifen in MCF-7 human breast cancer orthotopic model. There was statistically significant change in tumor growth with UPF/tamoxifen and FVF/tamoxifen. UPF, Undaria pinnatifida; FVF, Fucus vesiculosus.
Figure 4.
Figure 4.
(a) Summary of the combination of the fucoidans in combination with paclitaxel in ZR-75 human breast cancer orthotopic model. The figure represents the tumor growth rate day 0 to 28 days. There was statistically significant change in tumor growth with FVF/paclitaxel but decrease in tumor growth with UPF/paclitaxel. (b) Summary of the combination of the fucoidans in combination with tamoxifen in ZR-75 human breast cancer orthotopic model. There was statistically significant change in tumor growth with UPF/tamoxifen and FVF/tamoxifen. UPF, Undaria pinnatifida; FVF, Fucus vesiculosus.
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