Fucoxanthin derivatives from Sargassum siliquastrum inhibit matrix metalloproteinases by suppressing NF-kB and MAPKs in human fibrosarcoma cells

doi:2014.29.4.355

Algae > Volume 29(4); 2014 > Article

Algae 2014;29(4): 355-366. doi: https://doi.org/10.4490/algae.2014.29.4.355

Van-Tinh Nguyen¹, Zhong-Ji Qian², Bonggi Lee³, Soo-Jin Heo⁴, Kil-Nam Kim⁵, You-Jin Jeon⁶, Won Sun Park⁷, Il-Whan Choi⁸, Chul Ho Jang⁹, Seok-Chun Ko¹⁰, Sun-Joo Park¹¹, Yong-Tae Kim¹², GeunHyung Kim¹³, Dae-Sung Lee¹⁴, Mi-Jin Yim14, Jae-Young Je¹⁵ and Won-Kyo Jung^1,*

¹Department of Biomedical Engineering, and Centre for Marine-Integrated Biomedical Technology (BK21 Plus) Pukyong National University, Busan 608-737, Korea
²College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China
³College of Pharmacy, Pusan National University, Busan 609-735, Korea
⁴Global Bioresources Research Center, Korea Institute of Ocean Science and Technology, Ansan 426-744, Korea
⁵Marine Bio Research Team, Korea Basic Science Institute (KBSI), Jeju 690-140, Korea
⁶Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Korea
⁷Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, Korea
⁸Department of Microbiology, Inje University College of Medicine, Busan 614-735, Korea
⁹Department of Otolaryngology, Chonnam National University Medical School, Gwangju 500-757, Korea
¹⁰Institute of Marine Biotechnology, Pukyong National University, Busan 608-737, Korea
¹¹Department of Chemistry, Pukyong National University, Busan 608-737, Korea
¹²Department of Food Science and Biotechnology, Kunsan National University, Gunsan 573-701, Korea
¹³Department of Biomechatronic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 440-746, Korea
¹⁴Marine Biodiversity Institute of Korea, Seochun 325-902, Korea
¹⁵Department of Marine-bio Convergence Science, Pukyong National University, Busan 608-737, Korea

*Corresponding Author

Email: wkjung@pknu.ac.kr

ABSTRACT

Fucoxanthin is known to be an effective cell proliferation inhibitor with anti-tumor and anti-angiogenic activities. However, there is a lack of data regarding the biological effects of cis isomers of fucoxanthin. To assess the potential therapeutic properties of 9′-cis-(6′R) fucoxanthin (FcA), and 13-cis and 13′-cis-(6′R) fucoxanthin complex (FcB) isolated from Sarggassum siliquastrum, we investigated their inhibitory effects on matrix metalloproteinases (MMPs) in phorbol 12-myristate 13-acetate (PMA)-induced human fibrosarcoma (HT1080) cells. FcA and FcB reduced MMP-2 and MMP-9 protein and mRNA levels, as well as the migration of these cells, in a dose-dependent manner. Additionally, FcA and FcB increased levels of MMPs inhibition factors such as tissue inhibitor of metalloproteinase-1. FcA and FcB significantly inhibited the transcriptional activity of nuclear factor кB (NF-кB) and by inhibiting c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases. Our results demonstrate that suppression of the NF-κB, JNK, and p38 signaling pathways may inhibit PMA-induced MMP-2 and MMP-9 activity. Therefore, FcA and FcB may be useful in noninvasive therapeutic strategies against fibrosarcoma metastasis.

Key words: fucoxanthin; human fibrosarcoma cells (HT1080); matrix metalloproteinases (MMPs); mitogen-activated protein kinase (MAPK); nuclear factor-kappaB (NF-κB); Sargassum siliquastrum