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RESISTIVITY OF PROTEIN KINASE-B (AKT), NF-κB TRANSDUCTION OBSTACLES, AND APOPTOSIS INDUCTION (CASPACE -3, -9) AS ANTI-PROLIFERATION AND ANTI-CANCER OF BURKITT’S LYMPHOMA USING FLAVONOID FRACTION OF ETHYL ACETATE FROM ANT NEST (MYRMECODIA PENDANS)

Introduction: Burkitt’s lymphoma (LB) is a tumor with high malignancy and rapid cell growth and originates from B-cell lymphoma. LB is usually found in children in endemic areas with dengue fever and HIV-AIDS with low socioeconomic levels. Objective: This research aims to analyze resistivity of protein kinase-B (Akt), NF-κB transduction obstacles, and apoptosis induction (Caspace -3, -9) as anti-proliferation and anti-cancer of burkiit’s lymphoma using flavonoid fraction of ethyl acetate from ant nest (Myrmecodia pendans). Material and Methods: The study was conducted in a pure laboratory experimental method using burkitt’s lymphoma cancer cell culture. Gradual research begins with the determination, extraction and fractionation of ant nest plants, to test for proliferation barriers. Data analysis using two-way ANOVA followed by Post Hoc LSD test with a significance level of 95%. Pearson correlation test was conducted. Results: Resistivity of protein expression of protein kinase-B (Akt), transcription factor of nuclear factor-kappa B (NF-κB), and apoptosis induction (Caspace -3,-9) showed increased protein expression was significantly obstacles and prove that the ethyl acetate fraction flavonoid inhibits translocation and activation of transcription pathway NF-κB and growth factors that induces the phosphorylation of Akt signal transduction pathway, and apoptosis induction (Caspace -3,-9). Conclusion: Flavonoid fraction of ethyl acetate from ant nest (Myrmecodia pendans) resistivity of protein kinase-B (Akt), NF-κB transduction obstacles, and apoptosis induction (Caspace -3, -9) as anti-proliferation and anti-cancer of burkitt’s lymphoma.


INTRODUCTION
Cancer is a deadly disease and cause of death in industrialized countries and the second cause of death in developing countries. Cancer is a non-communicable disease, which is characterized by abnormal or persistent, and uncontrolled cell growth, which can damage the surrounding tissues and can spread to places far from their origin called metastasis. According to WHO data in 2013, the incidence of cancer increased from 12.7 million cases in 2008 to 14.1 million cases in 2012, with the number of deaths increasing from 7.6 million people in 2008 to 8.2 million in 2012. 1 Cancer that can cause enlarged lymph nodes is called lymphoma. Lymphoma is a general term for various types of blood cancers that appear in the lymphatic system.
According to the 2012 GLOBOCAN (IARC) data, lymphoma is one of the ten most cancers in the world in 2012. Non-Hodgkin's lymphoma occurs due to mutations that occur in the immune system caused by infectious agents, carcinogenic substances and a history of other diseases suffered by a person. 2

,3 Burkitt's Lymphoma is a type of Non-Hodgkin
Lymphoma. Burkitt's Lymphoma is a mature neoplasm of B lymphocyte cells and includes aggressive lymphoma. 4 The results of the study have shown that ant nest plants are one of the medicinal plants that are believed to have potential effects in the world of health. Although modern therapies such as chemotherapy give positive results in the treatment of cancer, on the other hand many cause side effects. Therefore, herbal treatment is often a cancer treatment option. In addition to the low cost, the side effects produced are also minimal compared to modern therapies. 5 Chemical screening tests for ant nest plants indicate that these plants contain flavonoid and tannin class chemicals. Many working mechanisms of flavonoids have been revealed, such as inactivation of carcinogens, antiproliferation, cell cycle inhibition apoptosis, induction Akt's signal activity, and NF-țB transduction obstacles. 6 Signal transduction is a process which begins by the activation of receptors located in the membrane (trans-membrane receptor) by the molecular signals from outside the cell, in turn will trigger a molecule in the cells secrete a particular response. The Akt protein, also known as protein kinase B (PKB) is one of the signal transduction protein kinase that plays a key role in several cellular processes, such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration. 7 The Akt proteins bind either PIP3 (phosphatidylinositol (3,4,5)-trisphosphate) or PIP2 (phosphatidylinositol (3,4) biphosphate). This is useful for controlling a mobile signal for dephosphorylation phosphoinositide (PIP2) only phosphorylated by the enzime family of PI3-kinase (phosphoinositide 3-kinase or PIK3) and after receiving chemical signals, then inform the cell to begin the process of growth. The PI3 kinase can be activated by G protein-coupled receptor pairs of tyrosine kinase receptors, such as insulin receptor. Once activated, the PI3-kinase phosphorylating PIP2 form PIP3-kinase (phosphoinositide 3kinase or PI3K). 8 Protein NF-țB is one member of the family transcription factors, which is important in the regulatory gene expression associated with biological functions as well as the immune response and inflammatory, growth and cell proliferation, as well as defense cell to stress (UV rays, irradiation, oxidants and DNA damage). The mechanism of NF-țB activation (Protein rail and p50) begins when the activation factor stuck to the receptor.
After the signal in the receptor, IKK protein (Inhibitory kappa beta kinase) will phosphorylate IkB" protein. While the NF-țB (Protein rail and p50) will be to the cell nucleus for gene transcription. 9 First, it inhibits protein kinase activity. Before the enzyme activity is excessive, the role of flavonoids is needed to prevent the formation of cancer cells, namely by preventing the joining of carcinogen compounds generated by the kinase enzyme with DNA, so that the DNA does not experience damage (cancer). Second, have anti-proliferation activity.
Third, it induces apoptosis. 10 Now, only a few potential anti-proliferation and anti-cancer agents such as flavonoids are known to cause apoptosis. This study was intended to analyze and identify the resistivity of protein kinase-B (Akt), NF-țB transduction obstacles, and apoptosis induction (caspace -3, -9) as anti-proliferation and anti-cancer of cell burkitt's lymphoma using of flavonoid ethyl extract on ant nests (Myrmecodia pendans).

MATERIAL AND METHODS
This study is a purely experimental laboratory study with a post-test control

DISCUSSION
Nature of cellular transmission is a system that is highly regulated in cancer cells, as well as recognizing that diseased processes are also a process that causes abnormal or abnormal growth. The growth signal circuit does not only regulate growth but also regulates various other cellular processes including differentiation, angiogenesis, migration, apoptosis. Various signaling molecules including the form of "kinase" including its case which holds an important role in cellulite processes. 11 Transactions of signals to control growth often depend on the ability of certain proteins to modify other proteins, often referred to as communication between proteins.