Haruan Fish Extract as Potential Agent for Cancer Therapy

Cancer occurs as a result of interconnected factors leading to disturbance in genomic composition of a cell [1]. The disturbance may be triggered by organismic, environmental and or genetic factors. These factors hijack the normal physiologic conditions of the cells like, cell division, cell differentiation, angiogenesis and cell migration to cause cancer [1]. Cancers are named base on their location in the body, for examples breast cancer, colon cancer, pancreatic cancer and prostate cancer all originated from breast, colon, pancreas and prostate gland respectively.

number of amino acids, peptides and proteins that may have antioxidant as well as anti-proliferative effects.

Haruan fish extract
Haruan fish, found in many tropical countries like Malaysia, Indonesia, and Thailand is widely known as a source of food and traditional medicinal product since pre-historic time [28]. Details of its bioactive component have been explored [15]. The components include proteins, peptides, glycoproteins, fat, and minerals [28]. Several amino acids and fatty acids were reported to be contained in Haruan fish extract (Table 1). Minerals deposit found in Haruan fish extract include magnesium, copper, calcium, manganese, iron, and zinc [29]. Nickel and lead were also reported to be found in the fish extract, but are much lower than the toxic threshold [29]. The peptides as well as the fatty acids, especially the unsaturated fatty acids, DHA and EPA content of this fish could give an effect on cytotoxicity and anti-oxidant activity. Therefore, the need to investigate the potential of this novel fish for anti-cancer activity would be attractive.

Anti-cancer activity of Haruan fish extract
Peptides and fatty acids derived from marine animals such as fish shows antioxidant activity [30], anti-proliferative activity [24] and antiangiogenesis [30]. Furthermore, several studies show that omega-3 fatty acids have significant effects on prevention, and suppression of different types of cancers incuding, colon, breast and prostate [31]. The important polyunsaturated fatty (PUFA) acids content of Haruan fish that are beneficial to anti-cancer studies include; EPA and DHA. Several experimental models and tissue culture studies reported the protective effects of theses omega-3 fatty acids on colon [21,24], breast [23][24][25][26] and prostate cancers [27][28][29]32].

Anti-oxidant potential
Cancer cells produce reactive oxygen species in abundant compare to normal cells [33]. These molecules attack lipids, proteins and DNAs there by causing serious diseases like cancer [22]. Peptides derived from marine fish proteins showed higher anti-oxidant activity than αtocopherol studied using variety of oxidative systems [34]. Haruan fish extract also possess anti-oxidant effects due to its omega-3 fatty acids content, especially EPA and DHA [35]. However, more research needs to be done to prove the mechanism of such effects.

Anti-angiogenic potential
Act of new blood vessel formation is termed angiogenesis. Cancer tumour growth relies on new blood vessel formation. In fact, it was elaborated that, for tumour to increase in size beyond 1-2 mm 3 there must be an equivalent formation of new blood vessel to cater for its nutritional needs.
EPA and DHA potentiate anti-angiogenic effects by limiting the secretion of necessary mediators of angiogenesis. Theses mediators includes, platelet-derived growth factor, endothelial cell growth factor, cyclo-oxygenase 2, prostaglandin-E2, and vascular endothelial growth factor [36].

Anti-cancer activities of omega-3 fatty acids in some selected cancer types
Breast cancer: Another important findings revealed that fish oil containing EPA and DHA successfully prevented breast cancer metastasis into the bone [4]. This support the claim that decrease in consumption of food rich in PUFA correlates with high risk of breast cancer in Japan [37]. Also, these polyunsaturated fatty acids have been reported to suppress breast cancer [38]. Furthermore, fish oil used to feed mice showed significant reduction in breast cancer tumour and in its spread to the lung [39]. All these evidences suggest that Haruan fish extract could have significant effects on prevention of breast cancer, as it contains the above named acids which play the key role on the prevention.
Prostate cancer: Omega-3 fatty acids were reported to prevent the development and progression of prostate cancer [40]. In fact, immunodeficiency mice fed with omega-3 dietary supplement show reduced level of tumour growth, final tumour volume and serum prostate-specific antigen level [41]. Berquine et al. reported the reduction in tumour growth, longer lifespan and slow histopathological progression of prostate cancer in Pten-knockout mice fed with omega-3 dietary supplement [42]. Another study shows that EPA and DHA specifically acts via 15-lipoxygenase-1 (15-LO-1) and cyclooxygenase-2 (COX-2) pathways to suppress prostate cancer progression [43].
As we mentioned earlier, both EPA and DHA are important components of Haruan fish extract. Since these fatty acids show therapeutic effects on prostate cancer, the extract can prevent prostate cancer if tested using the models highlighted in the text.

Colon cancer:
Haruan fish extract can also be explored for treatment and prevention of colon cancer. The reason being that, plenty of animal research models reported the involvement of omega-3 in suppression of colon cancer [19]. For instance, DHAwas shown to reduce primary tumour growth in human colon carcinoma xenograft nude mice [44]. Data from histological studies conducted further prove the reduction effect of the said fatty acid [44]. Furthermore, successful inhibition of metastasis was also reported in mice fed with omega-3 fatty acids [45].

Pancreatic cancer:
The therapeutic effects of omega-3 polyunsaturated fatty acids extend to pancreatic cancers. Again, (EPA) halts the development of human pancreatic cancer cell by inducing apoptosis [46]. Interestingly, the molecular mechanism of this apoptosis occurred through activation of caspase-3 and prevention of cyclo-oxygenase-2 expression [47]. Murine mice fed with dietary supplement containing omega-3 fatty acids successfully lessen the pancreatic pre-cancer by arresting the cell cycle in elastase (EL)-Kras transgenic mice [47].

Conclusions
The omega-3 fatty acid content of the Haruan fish extract, if found to be in an adequate quantity, has the potential to contribute to the treatment of various types of cancers including, breast, colon, prostate, and pancreatic cancers. This can be demonstrated using cell culture, animal models and human epidemiological studies as we exemplified in the text.
Moreover, the extract can achieve its anti-cancer activities by neutralizing the free radicals, inducing apoptosis and inhibiting angiogenesis. Considering the vast side effects caused by anti-cancer drugs as well as the drug resistance nature of cancer cells, it is necessary to search for safer and more specific drugs from natural products.