The oil palm fruit (Elaeis guineensis) contains large amounts of lipid or water soluble bioactive agents such as vitamin E (tocopherols, tocotrienols), carotenoids and phytosterols. The lipid-soluble tocotrienols are shown to have anti-tumor effects on human cancer cells like prostate, breast, colon, melanoma, and lung cancers. Water-soluble oil palm phenolics (OPP) have been demonstrated to show potential anticancer properties. Sambanthamurthi et al (2011) showed that phenolics inhibit tumour progression in tumour-inoculated mice; however there is no disclosure on tumour growth inhibition in pancreatic cancer using palm vegetation liquor. Sekaran et al (2010) have demonstrated that OPP can inhibit proliferation and induce apoptosis in different cancer cell lines such as breast, lung, and skin cancers in vitro. It was also found that OPP reduces tumor growth in vivo. However, there is no study available to disclose the effect of oil palm bioactive agents on pancreatic cancer cell growth. Therefore, it is an object of present invention to utilize the extract from this oil palm vegetation liquor in treating pancreatic cancer (PaCa).
Pancreatic cancer (PaCa) is one of the leading causes of cancer death with poor survival rate due to its aggressiveness and early metastases. Despite more focused research in this area recently, the mortality rate for PaCa has remained fairly high. The common treatments for PaCa patients are pancreatectomy, or surgical resection of the organ, followed by chemo, targeted and/or radiotherapies.
Gemcitabine is a purine analog which is used as a standard clinical chemotherapeutic agent for advanced PaCa treatment; however this agent has shown a poor tumor response rate with short survival time. Erlotinib is a targeting epidermal growth factor receptor tyrosine kinase which is used as an adjuvant to gemcitabine by inhibiting cell growth signaling but again showing marginally improved survival benefits in clinical trials.
Detrimental side effects of these chemotherapeutic agents available targeting PaCa such as heart attack, stroke and death have been documented. This results in limited advantage due to their dose limiting toxicity to normal tissues. Thus, it is an object of present invention to provide an alternative to enhance chemotherapeutic activity for pancreatic cancer with minimal adverse effects.
Another object of present invention is to curb the adverse effects and chemoresistance suffered by most gemcitabine-treated patients. It becomes crucial to develop a novel therapeutic agent in order to improve prognosis with natural plant extracts.
It is yet another object of present invention to provide a bioactive dietary agent used in combination with drug to achieve the pleiotropic effects which lessen the toxicity and dose requirements of therapeutics alone.
The nuclear factor κB (NF-κB) is widely used as a regulator of genes that control cell proliferation and cell survival, and it plays important roles in cancer cell transformation, cell invasion, and apoptosis. P65 is a subunit of NF-κB that interacts with promoter sequence of target genes which in turn induces the expression of genes involving in inflammatory, anti-apoptosis, and proliferation. This signaling pathway has been targeted as a strategy for anti-cancer therapy in PaCa patients. NF-κB is a common and constitutively expressed transcription factor which is activated through a wide variety of stimuli such as inflammation and oxidative stress. On stimulation, NF-κB is translocated to the nucleus and binds to the promoters of its target genes to begin transcription of specific genes. Overexpression of NF-κB may results in apoptosis resistance, angiogenesis, migration and invasion of cancer cells.
Studies have shown that NF-κB is constitutively activated in approximately 67% of pancreatic adenocarcinomas compared to normal pancreatic tissue, and this is associated with aggressive stage pancreatic cancer and drug resistance. Based on the role of NF-κB in regulating carcinogenic activity in pancreatic cancer and the anti-inflammatory behavior of palm vegetation liquor, present invention serves the purpose to describe the effect of palm vegetation liquor in pancreatic cancer cell model, characterized in the potential down-regulation of the NF-κB pathway.
Thus, it is yet another object of present invention to provide a composition for anti-proliferation in pancreatic cancer via regulation of NF-κB pathway.
It is a further object of the present invention to provide an improved composition and method based on compounds extracted from vegetation liquor i.e. aqueous stream of the palm oil milling process for providing inhibitory effect against pancreatic cancer.
Accordingly, present invention also relates to an extraction process of bioactives from the oil palm vegetation liquor from the milling process. The processing of oil palm produces large amounts of vegetation liquor rich in phenolic compounds, shikimic acid, fruit acids, fruit sugars and glycerol which can be further enriched using conventional membrane filtration technology.
Further objects and advantages of the present invention may become apparent upon referring to the preferred embodiments of the present invention as shown in the accompanying drawings and as described in the following description.