Sarang Semut (Myrmecodia Pendens) as anticancer agent

Indonesia is a nation passed by the equator line, an archipelago of more than 17000 islands. An exotic country with sixty percent of its land is covered by forest, making it one of the countries with richest biodiversity in the world. Scholars have estimated that Indonesia possesses around 30,000 plant species which only less than 5% being studied. The country has wide development gap, dividing the country into 2 extremities, with the western islands being more developed and the eastern archipelago underdeveloped. There are still many tribes in the island of Papua lives primitively as hunter and gatherers. These native tribes rely on vast knowledge about nature to maintain survival.

        Scholars around the world have always been interested in these primitive societies still existing in our current world. Some scholars show great interest in the traditional medication practiced by these societies, in hope to find potential for new source of therapeutic agents to answer most challenging questions in medical society, that is cancer.

        One of the identified medicinal plants is Sarang Semut (Myrmecodia pendens). The first information about this plant originated from empirical knowledge of local Papuan society located in Eastern Indonesia. They have been using Sarang semut plant as medication for various diseases such as ulcer, hemorrhoid, heart diseases, tumor, cancer, etc. Generally, this plant is consumed by drinking its boiled water.

        Sarang semut (Myrmecodia pendens) are tubers that grow hanging from branches of tall tree. The plant depends mostly on symbiosis with ants for its nutrients. The inside of the plant consists of small labyrinths perfect as ant nest. The plant provides the ants with safe habitat high up in the trees, protecting them from their predators. Meanwhile, the ants provide defense and nutrients for the plant by leaving waste materials inside the body of the plant, which can be absorbed and assimilated by the plant. Sarang semut plant is a member of the Rubiaceae family with 5 genuses, however, only 2 of which have association with ants. They are Myrmecodia and Hypnophytum. Of those species, only Myrmecodia pendens and Myrmecodia tuberose are considered to have medicinal value.

        Cancers are entitled immortal cells for its ability to evade programmed cell death or apoptosis. Every normal human cell has a specific lifespan governed by the intrinsic factor kept in our DNA. Our cell normally divides when necessary, and will undergo programmed cell death at the end of its lifespan, allowing newer cells to take its place. Not so in cancer cells. Cancer cells have accumulated mutation in their DNA to override the apoptosis action. Apart from being immortal, cancer cells also mutated in such a way that render them the ability to divide incessantly regardless of natural inhibiting signals such as cellular density and growth factors. These cancer cells develop the ability to stimulate growth by themselves through an autocrine pathway to self – producing the relevant growth factor. Nevertheless, as far as growth is the concern, nutrients are the limiting factor. Cancer cells provide nutrients to itself by a mechanism known as angiogenesis which literally means ‘growth of new blood vessels’. These cells secrete angiogenesis factor such as VEGF (vascular endothelial growth factor) and IL-8 among other angiogenetic cytokines. The new blood vessels will supply these cells with the necessary nutrients to resume growth and eventually spread to other part of human body, a mechanism known as metastasis. With all this process, cancer cells will kill its host by diverting nutrients to normal cells, incapacitating immune response (the natural cancer killer cells), and when spread to organ system, will cause multi-organ dysfunction syndrome.

        Knowing the characteristics and behavior of cancer cells, the way to fight cancer cells is to eliminate all cancer cells from the body, hence preventing the proliferation and spread of these cells totally. Many researchers and research centre have been putting tremendous time, resources, and efforts into finding the best cure for cancer. The progress so far is commendable, but killing of cancer cells through chemotherapy, radiotherapy or surgery will have to be done by compromising healthy cells, weakening the host even further. Current chemotherapies are potent, but lack selectivity to healthy cells. In view of this, many researchers are looking for cure provided by nature which kills cancer cells and at the same time harmless against normal cells. 

        Based on the traditional usage of Myrmecodia as anticancer agent by the Papuans, many researches have been conducted to prove its claim. From past in vitro researches, it was proven that extract from Myrmecodia suppresses the expression of mutated p53 gene from breast cancer cells from T47D line. Besides that, it also exhibits anti – proliferative activity against cervical, lung, and colon cancer. Based on that evidence, local researchers hypothesize that Myrmecodia will express anticancer activity when tested in vivo, or in living animal.

        A study done in University of Padjadjaran Indonesia involves live animal, using 28 rat labs of C3H line divided into four groups. One group as control, while the other three will be given extract of Myrmecodia of different dosages. Adenocarcinoma cells are inoculated into these rats. After growing the specific tumor, each rat is given the extract of Myrmecodia of different dosages: 4mg/ day, 8mg/ day and 16mg/day. The result of the experiment suggests anticancer activity of Myrmecodia. In terms of apoptotic index, all Myrmecodia treated group of rats reflect increasing apoptotic index as compared to control group. The increase in apoptotic index in treated groups is related to the stimulation of interferon gamma by the plant’s flavonoid. This in turn increases the activation of T lymphocytes and natural killer cells to provide defense against cancer cells. The experiment also shows that the group treated with the highest dose of Myrmecodia extract reflect faster apoptotic rate to exceed the rate of tumor growth.

        Similar studies are done by Arius et al in 2011, revealing that when Myrmecodia extract is given at IC (Inhibitory Concentration) amount to 539,902 microgram / milliliter, it can inhibit until 50% the growth of breast cancer cells. When the extract is increased with Effective Concentration (EC) 50 at 1599,998 microgram / milliliter, it can kill cancerous cells until 50%. This finding provides new possibility of specific chemotherapy which do not harm healthy cells.

        Another study by Harun et al in 2014 reflects that extract of Myrmecodia also reflect effectiveness against Human tongue cancer of the SP-C1 line type of squamous cell carcinoma. The study reflects correspondingly higher rate of inhibition with higher dosage of the flavonoid extract.  In this study, the effect of Myrmecodia extract on the expression of VEGF and IL-8 is measured. The result prove to be as expected, that cancer cells treated with the extract reflect inhibition of VEGF and IL-8 expression, which are two main cytokines involved in angiogenesis. Hence, it can be concluded that Myrmecodia is exhibiting anti angiogenesis activity. By reducing the VEGF expression, the cancer cells will also be forced into senescence or cease of activity, by stopping the cell cycle.

       Study by Soeksmanto et al in 2010 shows that extract of Myrmecodia also exhibit tumor suppressing activity against cancer cells of HeLa and MCM-B2 type. The result showed that water extract of Myrmecodia has better anti cancer activity compared to the other extraction methodologies. They concluded that polar extract exhibited higher anticancer activity than non – polar extracts.

        Another interesting study is conducted by Adam et al in 2014, to identify key antioxidants in Myrmecodia extract. The method involves using UV/visible spectrophotometer, liquid chromatography tandem with mass spectrometry, and high performance liquid chromatography. From this study, three major phenolic compounds were identified: rosmarinic acid, procyanidin B1, and polymer of procyanidin B1. These potent antioxidant agents found in Myrmecodia or sarang semut are responsible to fight against damages attributed to oxidative stress by free radicals. Besides its anticancer activity, the extract of this plant are source of potent antioxidant to prevent cellular damage and mutation and preventing cancer.

        Further study is conducted by Triana et al in 2014 on the immunomodulatory effect of Sarang semut or Myrmecodia. The study used water based extraction of Myrmecodia. Lymphocyte proliferation was observed by the MTT reduction method and analyzed using microplate reader at 550nm. Macrophage phagocytosis activity was determined based on the number of latex beads uptake by the macrophage cells. The result shows that the extract significantly increased the lymphocytes proliferation and macrophage phagocytosis activity in comparison to negative control. Hence it can be concluded that Myrmecodia are potential immunomodulatory agents.  This result is further supported by the study done by Sumardi et al, which shows that the hypocotyl extract of Myrmecodia modulates TCD4+ and TCD8+ cell profile in doxorubicin – induced immune suppression rats in vivo.

        The studies of Myrmecodia, a medicinal plant with long history of usage by the Papuan tribe are still early considering the relatively new finding of this exotic plant exclusively at Papua island of Indonesia. Nevertheless, all results seem promising and proving that the history – proven Myrmecodia is indeed effective against cancer cells. As more researches will be done in the future, the world may welcome the highly potential anti cancer agent from Indonesia.

        Many cancer patients have been using the extract of this plant to cure themselves of the ailment. For example, Mr. Afril was diagnosed with type AML M3V leukemia from the BMP (Bone Marrow Puncture). After consuming the extract of Myrmecodia for 2 months, leukocyte counts begin to decrease, and on the third month, it returns to normal. Mrs. Dewa, was diagnosed with early stage skin cancer on her forehead. After consuming the extract of Myrmecodia for 6 weeks, the tumor shrunk and healed. Mrs. Nita was diagnosed with breast cancer, and in 1 month of therapy, the tumor shrunk in and her conditions improved. There are many other testimonials by people using this therapy on the effectiveness of Myrmecodia pendens or Sarang semut extract, as an anticancer agent.

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