吃褐色海藻可能预防黑色素瘤

Seaweed specific studies of inhibition of melanoma

Seaweeds have been studied in vitro and in vivo and several extracts have shown efficacy at the inhibiting formation of many forms of cancer. Although there have been more than 250 studies of seaweeds and cancer, few have focused on melanoma (PubMed, 5 August, 2016). These studies are presented in Table Table1.1. Melanoma cells are relatively easy to grow in cell culture and in animal models. They readily metastasize providing informative models for human melanoma. However, the applicability of results from cell culture to humans is tentative. Many of the natural defense mechanisms of the complex human body play an important role in mitigating the effects of carcinogens and anti-carcinogens. Likewise, the commonly used mouse melanoma model appears to be good at studying the metastatic behavior of melanoma cells but lacks the mechanisms of UV initiation and modulation of the cancer process. It is therefore extremely attractive to examine population patterns of melanoma to discern information about melanoma in human.

The best known of the anti-carcingenic seaweed extracts is fucoidan. Several animal studies show fucoidan inhibits melanoma in vitro and in vivo (Koyanagi et al. 2003; Ale et al. 2011a, 2011b; Croci et al. 2011; Vishchuk et al. 2012; Jin et al. 2014; Anisimova et al. 2015). These are presented in Table Table11. Cumashi et al. (2007) reviewed the many anti-inflammatory, anti-coagulant, anti-angiogenic, and anti-adhesive activities of fucoidans, and although varying slightly between the nine species examined, generally concluded that fucoidans could be helpful in improving health. A study supporting a role for fucoidan in photoprotection was done by Anisimova et al. (2015). They reported a 1.9-fold increase in cytotoxic activity of spleen mononuclear leucocytes towards melanoma cells of line B16 and concluded that one of the ways seaweed fucoidan could influence antitumor activity was as an effector of the innate immune system via CD11c integrins. Fucoidan has been studied as both an anti-carcinogenic agent on its own and as an adjunct to conventional therapies (Kwak 2014; Abu et al. 2015; Atashrazm et al. 2015). A study of 70 elderly subjects who were presumed to have age-related immune suppression were randomized to either a daily dietary supplement of 300 mg fucoidan or placebo given as an adjuvant to standard seasonal influenza vaccine. There was a significant enhancement of natural killer cell activity associated with fucoidan but no increase in the group given the placebo (Negishi et al. 2013). As the most effective treatments for late stage melanoma involving immunotherapy that results in increasing natural killer cell activity, this study is supportive of a role for dietary fucoidan in melanoma treatments.

Several studies have reported that seaweed extracts inhibited melanogenesis in mouse melanoma cells, and should be considered for use in cosmetics for skin lightening (Kim et al. 2013; Jin et al. 2014; Song et al. 2015). Since lighter skin is a risk factor for susceptibility to melanoma, the activity of fucoidan may not be helpful. However, Maruyama and colleagues reported that dietary Undaria sporophyll (mekabu) was associated with significant suppression of the inflammatory response to UVB exposure in mice (Maruyama et al. 2015). Perhaps it could be both an inhibitor of melanogenesis and its pro-inflammatory reaction to UV light as well as a photoprotector against the DNA damage that may cause melanoma.

A study of a polysaccharide compound from Ascophyllum sp., reported to be different in chemical composition from fucoidan, has also been reported to have immune stimulating activity against melanoma (Abu et al. 2015). Invasion and migration of melanoma tumor cells were inhibited in vitro and lung metastases were inhibited in vivo.

Dietary carotenoid intake has been associated with reduced risk of melanoma (Millen et al. 2004). Fucoxanthin is the major form of carotenoid found in brown seaweed chloroplasts, where it is part of the light-harvesting complex algae use for photosynthesis and photoprotection. It accounts for about 10 % of all natural carotenoids found in nature (Miyashita et al. 2011). Animals cannot synthesize carotenoids but must obtain them from their diet. Fucoxanthin has an unusual shape with an allenic bond found in only about 40 of the more than 700 different naturally occurring carotenoids. This may account for its wide range of biological activities including thermagenesis, anti-obesity, anti inflammatory, and anti carcinogenicity (Miyashita et al. 2011; Kumar et al. 2013; Mikami and Hosokawa 2013). The data for specific anti-melanoma activity include four studies demonstrating significant inhibition of melanoma in vitro and in vivo (Shimoda et al. 2010; Chung et al. 2013; Imbs et al. 2013; Kim et al. 2013; Thomas and Kim 2013; Wang et al. 2014). Although not specifically melanoma studies, several authors have reported fucoxanthin (either orally or topically applied) reduced UVB-induced skin inflammation in vitro and in vivo, and was important in skin whitening (Lee et al. 2013).

Phlorotannins are phenolic compounds that are part of the structural components of brown algae cell walls. They are produced by seaweeds in response to high UV-B radiation and grazing threats. They have been studied as possible sources of sunscreens and other beneficial bioactive compounds (Li et al. 2011). In particular, phlorotannins have been studied as tyrosinase inhibitors in melanoma cells although the intent of the studies was to identify skin lightening compounds in seaweeds, rather than to act against melanoma tumors (Yoon et al. 2009; Kang et al. 2012).

Prebiotics have recently emerged as an important defense against cancer. In humans, the intestine hosts about 10¹⁴ bacteria, or about ten times the number of human cells in an average human (Gerritsen et al. 2011). The role for intestinal bacteria in melanoma has recently emerged. In a study of two groups of rats given a melanoma immunotherapy (programmed cell death-1 inhibitor) (PD-1 blocker), it was discovered that rats with gastrointestinal populations of Bifidobacterium longum had the same tumor control as those rats administered the anti-PD-1 therapy that was being studied. Oral administration of Bifidobacterium to rats without this intestinal bacteria was effective in inducing the same response, and the combination of Bifidobacterium and anti-PD-1 therapy almost abolished tumor growth (Sivan et al. 2015).

Dietary seaweeds have been found to have significant prebiotic effects that influence Bifidobacteriumpopulations (de Jesus et al. 2016). Wang reported that 2.5 % alginate supplementation in rats increased Bifidobacterium by 13-fold compared to the control group (Wang et al. 2006). An et al. (2013) investigated the effects of two of the primary fermentable seaweed polysaccharides on the relative abundance of microbiota in the caecal contents of rats fed a control (no fiber), a 2 % alginate diet, and a 2 % laminarin diet. They reported that alginate was associated with a four-fold increase from 1 % in the relative abundance of the bacteria in the Actinobacteria phylum but a decrease to 0 % in the laminarin supplemented the diet. Bifidobacterium, although a member of the Actinobacteria phylum, was not specifically identified. Interestingly, red seaweeds appear to have a similar effect in increasing Bifidobacterium in animal studies using 2.5 % Chondrus crispus (4.9-fold increase) in a rat study (Liu et al. 2015). A 1 % supplementation with Sarcodiotheca gaudichaudii in a chicken study was associated with a 14-fold increase (Kulshreshtha et al. 2014).

Alginic acid has been used for decades as an over the counter treatment for stomach hyperacidity (Malmud et al. 1979; Holdt and Kraan 2011). The mode of action is to combine with stomach acid to form a floating raft above the stomach contents, thereby reducing stomach acid reflux. A study of healthy male volunteers reported that a daily intake of 10 g day⁻¹ of alginate was associated with a significant increase in fecal Bifidobacteria (Terada et al. 1995). In a general comparison of fecal excretion of diverse bacteria, 106 healthy Japanese volunteers had almost 20-fold higher excretion of Bifidobacteria than people from 11 other countries studied (Nishijima et al. 2016). These studies provide circumstantial evidence for a possible role of dietary seaweed in enhancing Bifidobacteria populations in people who consume brown seaweeds, possibly contributing to protection against melanoma.

It is also possible that eating brown seaweed increases available fucose (Cao 2015). Protein fucosylation is key to immune cell recognition, cell signaling, and general health, and reduced cell surface fucosylation sites on melanoma cells have been reported (Lau et al. 2015). Lau and his colleagues reported that oral L-fucose (drinking water) fed to mice with melanoma restored fucosylation in the melanoma tumors leading to about a 300 % increase in the number of intratumoral natural killer cells and decreased metastases. In the same study, the authors reviewed tumor tissue samples from 320 human melanoma patients. Higher expression of melanoma cell surface protein fucosylation was associated with improved overall survival and 34 % lower risk of metastases. The exact mechanisms of action are still being investigated. Bioavailability studies of brown seaweeds have focused on fucoidan, rather than fucose (Irhimeh et al. 2005; Warttinger et al. 2016). Fucose availability after eating raw seaweed is negligible but if seaweed is digested by heat or enzymes, as is likely with dietary seaweed, or gut microbes following ingestion, then free fucose would be made available. The fate of fucose in the gut is to cross the membranes by diffusion or to bind with certain cells (M) in Peyers’s patches and modulate the immune system.