Coconut: Natural Source of Potential Anti Cancer Agent

The current strategy of drug development is time consuming and expensive. This contrasts sharply with the vision of affordable drug development. The costly and the lengthy paradigm of drug discoveries are major obstacles for combating with rapidly emerging and sporadic diseases. The dichotomy between the urgent requirement of affordable treatment development and the hindrance it faces is apparent in several recent literatures which reflects the importance of drug repurposing and development of botanical drugs. Consistent with this idea, past few decades of studies on Cocos nucifera has yielded a fair knowledge about the anticancer potential of coconut products. The aggregate knowledge is undeniably positive and offers the novel avenues for the therapeutics and affordable drug development. This article highlights the link between coconut products and its anticancer effects.


Introduction
One third to half of all pharmaceuticals drug are originally derived from plants. Natural products are the source of 60% of currently used anticancer products and some of natural products are under clinical trial (http://www.clinicaltrials.gov/). PubMed search shows countless article regarding the health benefit of coconut. Curated preventive role of virgin coconut oil (VCO) and coconut water (CW) in cancer, cardiovascular, neuronal, mental and metabolic diseases are reflected in several in vitro and in vivo studies. But underlining causes of these therapeutic effects are yet to be explored. The virgin coconut oil and green coconut water have interesting anti-cancer activity. In spite of the miraculous health beneficial effect and potential marketing opportunity, Cocos nucifera products did not significantly translated into everyday health care products and medicines. This is because most effort of drug development efforts are focused on synthetic compounds.
After publication of the FDA's industry guidelines for botanical drug product in June 2004, first botanical product Veregen (sinecatechins) was approved by FDA on 31 st October 2006 for marketing. Veregen was prepared from green tea leaves and approved for the topical treatment of perianal and genital condyloma. Approval of veregen by FDA was instrumental in the steadily growing interest for launching of other botanical drug products. Many botanical products are used over thousands of years (due to its beneficial purpose) but according to present FDA rules, identifying the different medicinal properties of its compounds and using them for the formulation of health care products will help in getting approval for its marketing for the treatment of specific health condition. New thinking is needed to address this challenge.
In this review we revisit the history of anticancer potential of VCO and summarize the recent finding to expand our understanding about anticancer effect of coconut water. This information will help to understand the mechanism of action and also encourage other research groups to conduct further translational research in this field.
Much remains to be discovered with regard to nutritional based treatment. But interpreting the published literature clearly indicates that coconut products function like double edges of a sword -Nutritionally it can prevent cancer and it is also a source of potent anticancer molecules (Table 2 & 3). Anticancer properties of coconut oil were also reported by Lim-Sylianco in 1987, in his published 50 years literature review and by Cohen et al. in 1986. Coconut oil is also anti-carcinogenic (1, 2).
As any promising domain of biology it is better to start with phenotype and then ask "why," to explore the underlining causes. Anticancer properties of Virgin coconut oil (VCO) are imparted because of its high percentage of medium chain fatty acid. The coconut oil which is composed of 92% saturated fatty acid, are predominantly medium chain fatty acids in the form of triglyceride (MCT) and 8% of unsaturated consisting of oleic and linoleic acid as triglycerides. Due to high fat and low carbohydrate composition it can be considered as a ketogenic diet (KD), consumption of which forces the body to burn fat rather than carbohydrate. Ketogenic diet reduces the frequency of epileptic seizures and includes treatment for several rare metabolic disorders. Several published articles have reported the anticancer effect of ketogenic diet (Table 1).
Due to inefficiency of cancer cell in processing ketone bodies for energy, ketogenic diet are effective for cancer treatment. Consumption of ketogenic diet results in carbohydrate restriction and consequently decreases the serum glucose and insulin level followed by increase in lipolysis. Fatty acid activate the peroxisome proliferator-activated receptor α (PPARα). PPARα increase fatty acid oxidation and ketogenesis as well as inhibit fatty acid synthesis and glycolysis (13,14).
Both Insulin and IGF-1 activates the phosphatidylinositol-3 kinase (PI3K)-Aktmammalian target of rapamycin complex 1 (mTORC1) signaling pathway. This pathway promotes sustained proliferative signaling, resisting cell death and modulates cellular mechanism which are the hall mark of cancer. Ketogenic diet means carbohydrate and protein restriction which results in drop of insulin level and less bioavailability of IGF-1 respectively. As a result (PI3K)-Akt-mTORC1 signaling pathway are not activated (16). mTORC1 also inhibit the PPARα and downregulate ketogenesis (17). Interestingly ketogenic diet also modulates the cell signaling pathways, which are also the target of some anticancer drugs (14). Adding fresh coconut into daily dishes will be the nontoxic alternative cancer treatments.
It was reported long before that coconut oil is composed of fatty acids, sterols and cytokinins. Among sterol in coconut oil, betasitosterol are most abundant. Oral bioavailability of β-sitosterol is 36.9%. It inhibits proliferation and induces apoptosis in breast cancer cell MCF-7 and human leukemic U937 cells (18,19,20). It activates caspase-3 and Bax/Bcl-2 ratio U937 cells.

Trans-Zeatin inhibit UVB-induced MMP-1 expression and may have anticancer role (45).
The latest addition is anionic peptide Cn-AMP2 (TESYFVFSVGM) which was isolated from green coconut water and it inhibits the proliferation of 1321N1 (IC 50 =1.25 mM) and U87MG (IC 50 =1.85 mM) human glioma cell lines. Cn-AMP2 has anticancer activity against human glioblastoma and may be used for treatment against other cancers (46). These results highlight the previously unnoticed link between coconut products and its promising anticancer effects. It also indicates the possible other therapeutic potential of cytokinin. We are unable to analyze the pathways and diseases enrichment for Trans-Zeatin, Transzeatin riboside, benzyladenosine due to insufficient information. Based on accumulating information, it is clear that the beneficial effects of some cytokinins are yet to be explored. Incorporating this modern knowledge into design the novel treatment could be effective in combating cancer and other diseases.