Polysaccharide Found in Seaweed Shows Anti-Tumor Effects on Prostate Cancer

by | Jul 19, 2018 | 2017, Men's Health, Prostate Cancer

Written by Angeline A. De Leon, Staff Writer. Fucoidan, a marine plant extract, displayed significant anti- angiogenic and anti-tumor effects on human prostate cancer cells in vitro and in a mouse xenograft model, and clarified a possible role of the JAK-STAT3 pathway.

prostate cancerAccording to recent reports, prostate cancer now represents the most common type of cancer among American men 1. Pathogenesis of prostate cancer involves a complex set of risk factors, such as age, genetics, and sexual exposure 2. At the physiological level, activation of the JAK-STAT3 signaling pathway (involved in immunity, cell division, and cell death) is critical to the metastatic progression of prostate cancer 3. Abnormal activation of JAK-STAT3 is associated with unregulated cell proliferation, tumor angiogenesis (formation of new blood vessels), and metastasis 4. While therapeutic interventions for prostate cancer have largely focused on targeting the JAK-STAT3 pathway, complementary and alternative practices continue to explore natural options for deep immune stimulation. One promising bioactive ingredient extracted from food is fucoidan, a polysaccharide obtained from species of brown algae and seaweed 5. Studies have linked the natural food compound with anti-tumor activity on liver, colon, lung, prostate, and bladder cells 6. In a major trial, fucoidan also demonstrated the capacity to induce cell death in human prostate cancer cells in vitro 7. The in vivo effects of fucoidan, however, remain unknown. In a study 8 published by BMC Complementary and Alternative Medicine, researchers in China studied the protective role of the JAK-STAT3 pathway in rodents as well as the potential anti-tumor and anti-angiogenic effects of fucoidan on cancer cells.

Androgen-independent cell-based assays and mouse xenograft model, as well as to clarify possible role of JAK-STAT3 were cultured for 24 hours and then treated with 100, 200, 500, and 1000 µg/mL of fucoidan (powder form dissolved in phosphate buffer saline) for another 24 hours. Cell viability and proliferation as well as cell migration and tube formation (processes involved in angiogenesis) were studied using cell-based assays. A total of 12 five-week old athymic nude mice were randomly assigned to receive a vehicle solution (saline) or fucoidan (20 mg/kg) by oral gavage for 28 days. Tumor cells were then subcutaneously injected into mice, and tumor size and volume measured every four days. Animals were sacrificed and tumor tissues were harvested and analyzed to determine protein expression of transcription factors JAK and STAT3.

Results indicated that 100, 200, 500, and 1000 µg/mL of fucoidan inhibited viability of DU-145 cells in a dose-dependent manner (inhibition rate of 11.5%, 26.7%, 50.7%, and 80.2%, respectively; p-value of < 0.01, < 0.001, < 0.001, < 0.001 vs. control, respectively). Similarly, 200, 500, and 1000 µg/mL of fucoidan were associated with inhibited proliferation of DU-145 cells in a dose-dependent fashion (inhibition rate of 30%, 57.8%, and 90.2%, respectively; p-value of < 0.001 vs. control for all). Chemical assays revealed that 500 µg/mL of fucoidan significantly inhibited the migration of cells (to the other side of a collagen-coated polycarbonate filter) (p < 0.001 vs. control) and significantly reduced the length of formed tubes (around a gelatinous protein matrix) (p < 0.001 vs. control). At the end of treatment, the fucoidan group, relative to control mice, also showed significantly lower tumor size (192.3 +/- 28.1 mm3 vs. 509.2 +/- 64.0 mm3, p < 0.001) and tumor weight (244.7 +/- 58.8 mg vs. 620.0 +/- 88.1 mg, p < 0.001). Finally, Western blot results indicated that protein expressions of (phosphorylated) JAK and STAT3 in tumor tissue were significantly reduced after treatment with 20 mg/kg of fucoidan (p < 0.01 and p < 0.001, respectively).

Taken together, findings from the mouse xenograft model of prostate cancer in this study indicate that the marine plant extract fucoidan is associated with significant anti-angiogenic and anti-tumor effects. Results also confirm the favorable impact of fucoidan on the JAK-STAT3 pathway in tumor tissue, suggesting that reduced phosphorylation of both JAK and STAT3 may play a role in the protective effects of fucoidan. Overall, fucoidan appears to be a promising alternative treatment for prostate cancer and deserves further study in human subjects.

Note: The doses of fucoidan used in this study are very high and NOT physiologically possible in humans. The lowest dose used (200 ug/ml) is equivalent to 200 mg/kg body weight which is 20 grams per day for a 100 kg person.

Source: Rui X, Pan HF, Shao SL, et al. Anti-tumor and anti-angiogenic effects of Fucoidan on prostate cancer: possible JAK-STAT3 pathway. BMC Complementary and Alternative Medicine. 2017; 17: 378. DOI: 10.1186/s12906-017-1885-y.

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)

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Posted July 19, 2018.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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