J. Appl. Phycol. 2017. Vol. 29, N 1. P. 543–553. doi: 10.1007/s10811-016-0915-3

In vitro anticancer activity of the laminarans from Far Eastern brown seaweeds and their sulfated derivatives

Malyarenko O. S.*, Usoltseva R. V., Shevchenko N. M., Isakov V. V., Zvyagintseva T. N., Ermakova S. P.

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of Russian Academy of Sciences (www.piboc.dvo.ru), 159 100-Let Vladivostok Ave., 690022, Vladivostok, Russian Federation.

* Author to whom correspondence should be addressed: Olesya S. Malyarenko, E-mail: malyarenko.os@gmail.com



Brown seaweeds have drawn worldwide attention due to their involvement in many industrial applications. They produce neutral low molecular weight polysaccharides (laminarans) with beneficial biological activities. However, the anticancer activity and molecular mechanism of the laminarans and their sulfated derivatives have not been investigated in detail.

Herein, the laminarans from brown seaweeds Saccharina cichorioides Miyabe, Saccharina japonica Areschoug, and Fucus evanescens C. Agardh were isolated. The laminarans from S. cichorioides and S. japonica were confirmed to contain a main chain of β-(1→3)-D-glucopyranose with single branches at C6. The laminaran from F. evanescens consisted of not only β-(1→3)-linked D- glucopyranose, but also includes single β-(1→6)-linked D-glucose residues. The branches at C6 are presented as glucose or as gentiobiose. The sulfated laminarans with different degree of sulfation were obtained by the chlorosulfonic acid – pyridine assay. In modified polysaccharides the positions of sulfates are directly predetermined by the structure of native laminarans.

The laminarans and their sulfated derivatives inhibited proliferation, colony formation, and migration of human colorectal adenocarcinoma, melanoma, and breast adenocarcinoma cells in different manner. The sulfated laminaran from F. evanescens possessed the highest anticancer activity in vitro and effectively prevented migration of breast adenocarcinoma cells by inhibiting of the Matrix Metalloproteinases 2 and 9 activity.

Keywords: Brown seaweeds, laminaran, sulfated derivative, anticancer activity, MMP-2, MMP-9.



Metastasis is cause of 90% of deaths against cancer, and it is the most challenging obstacle to successful cancer treatment [1]. The migration of cancer cells is integral part of the metastasis process which is realized by Matrix Metalloproteinases (MMPs). MMPs digested various components of extracellular matrix (ECM), including collagen, laminin, fibronectin, vitronectin, elastin, and proteoglycans. Of this diverse family of enzymes, MMP-2 and MMP-9 (also known as gelatinase A and gelatinase B, respectively), play an important role in the degradation of basement membrane type IV collagen, which is associated with tumor cell invasion and metastasis [2]. Therefore, the development of anticancer drugs, which regulate activity and expression of MMP-2 and MMP-9, is crucial in prevention of tumor invasion and metastasis.

The marine algae are ancient photosynthetic organisms that constitute the largest group in the plant kingdom. They are used for functional food, cosmetic additives, supplements productions, and in traditional medicine due to taste, prophylactic, and therapeutic effects [3].

The laboratory of Enzyme chemistry of PIBOC FEB RAS has long-term experience in the field of investigations of biologically active polysaccharides from brown algae, namely, laminarans, fucoidans, and alginic acids.

In the current study the laminarans from Far-Eastern brown seaweeds Saccharina cichorioides, Saccharina japonica, and Fucus evanescens were isolated, purified, and structurally characterized using modern chemical and physical technique. Laminarans were shown to consist of β-(1→3; 1→6)-inked D-glucose residues. They differ from each other with regard to their length and branching structure. The laminaran from F. evanescens has complex structure and contain some 6-O-branches in their main chain and some β-(1→6)-intrachain links.

Because the sulfated polysaccharides and their oversulfated derivatives were proved to possess high anticancer activity, we modified native laminarans by chlorosulfonic acid – pyridine method and have obtained sulfated laminarans with different degree of sulfation.

The study on the antiproliferative activity of native laminarans and their sulfated derivatives revealed the inhibiting activity of native laminarans was comparable with the activity of their sulfated derivatives (Fig. 1A).



Figure 1. The effect of the laminarans from S. cichoriodes (ScL), S. japonica (SjL), and F. evanescens (FeL) and their sulfated derivatives (ScLs, SjLs, and FeLs) (200 µg/mL) on cell proliferation (A) colony formation (B), migration (C), and activity of MMP-2 and MMP-9 (D) of human colorectal carcinoma HCT 116, melanoma SK-MEL-5, and breast adenocarcinoma MDA-MB-231cells.


The investigated laminarans and their sulfated derivatives were found to significantly suppress colony formation (Fig. 1B) and migration of colorectal carcinoma, melanoma, and breast cancer cells (Fig. 1C). The inhibiting activity of sulfated laminarans from F. evanescens was the highest among all other tested polysaccharides. We supposed that such potent anticancer activity of this sulfated laminaran may be related to its high degree of sulfation and content of β-(1→6)-O-glycosidic bonds, as well as peculiarities of molecular structure of this polysaccharide. The molecular mechanism of antimetastatic action of the laminaran from F. evanescens and its sulfated derivative was studied. As shown in Figure 1D, native laminaran did not block activity of MMP-2 and MMP-9 at concentrations up to 200 µg/mL, however sulfated laminaran effectively suppressed activity of MMP-2 by 17, 38, and 42 % and MMP-9 by 16, 27, and 31 % at concentrations 50, 100, and 200 µg/mL, respectively (Fig. 1D).

Taken together, we have demonstrated in vitro anticancer activity of the laminarans isolated from brown seaweeds S. cichorioides, S. japonica, and F. evanescens, which are widespread in the Far East, and their chemically sulfated derivatives through evaluation of their efficacy in inhibiting of proliferation, colony formation, and migration of human colorectal adenocarcinoma, melanoma, and breast adenocarcinoma cells.

Our findings indicate that sulfated laminarans may be one of the therapeutic approaches to treat cancer.



  1. Klein, C. A. (2008). Cancer. The metastasis cascade. Science, 321(5897), 1785-1787.
  2. Sternlicht, M. D., and Werb, Z. (2001). How matrix metalloproteinases regulate cell behavior. Annual Review of Cell and Developmental Biology, 17, 463-516.
  3. Menshova R. V., Shevchenko N. M., Imbs T. I., Zvyagintseva T. N., Malyarenko O. S., and et. al. (2016) Fucoidans from Brown Alga Fucus evanescens: Structure and Biological Activity. Frontiers in Marine Science, 3, 1-9.



This work was supported by Russian Science Foundation (RSF) No: 16-14-10131.


Figure 2. The authors with other members of the Laboratory of Enzyme Chemistry PIBOC FEB RAS