Annona Muricate and Annonaceous Acetogenins
For the past decades cancer death has increase and remained one of the most high risk health concern in the world. According to the American Cancer Society, in 2019, there will be an estimated of 1,762,450 new cancer cases diagnose and 606,880 cancer death in the United States. Cancer occurs because of several changes in cell physiology that eventually replicate and produce harm to the body. There are more than 100 types of cancer, found in the human body aside from the most commonly diagnosed cancer including breast cancer, prostate cancer and lung cancer.
Although, prognosis have improved with therapy, several limitations continue to play a crucial role. The most common treatments include surgery, radiation therapy, chemotherapy, immunotherapy, target therapy, stem cell transplant and medication. However, for some individuals the use therapies seemed to create resistance to the treatment. Thus, several studies have begun to focus on the importance of plant-based drugs who significantly have shown to contribute to anticancer drug discoveries.
For long time, the use of plant based medicines have been used all over the world to treat diseases and several body aliments which have revealed to possess an optimistic approach to pharmacological properties. Therefore, this study explores the effect Annona muricata has in stimulating anticancer agents in the body.
The Annona muricata (A. Muricata) is widely known as the soursop fruit, guanabana, or graviola is native to the Central and South American tropics, Western Africa and Southeast Asia. This fruit flourishes from the Annona muricate tree and gives a taste combination of sour and sweet. A. muricata flavor has been characterize as a strawberry and pineapple. It’s size and shape can be describe oval green covered with spikes on the outside. The inside is white with a sweet flesh containing 55-170 black large seeds. The taxonomic classification of this fruit is a kingdom of Plantae. A. muricata is commonly used to prepare candies, syrups, and beverages. Furthermore, A. muricata fruit and leaves are currently used in native cultures as a medicinal fruit.
The A. muricata for years have been recognize to help reduce fever, stomach aches, parasites and other health concerns. A. muricata have been receiving great popularity across the nation due to its biochemical pathway of being anticancer fruit. Several Studies have shown certain compounds and chemicals extracted from the leaves, seeds, bark and fruit itself appear to have a positive correlation to act as an anti-cancer agent. Approximately, 212 phytochemical ingredients have been extracted from A. muricata organism and have shown to induce apoptosis and inhibition of proliferation on variety of cancer cell lines including, breast, colon and liver cancer.
Annonaceous Acetogenins (ACGS)
One of the major constituents extracted in A. muricata is annonaceous acetogenins (ACGs). ACGs are derivatives of a long-chain fatty acids. A unique class of ACGs that has been detected are the C-35/C-37 fatty acids. They are combined with a 2-propanol unit at C-2 that forms a methyl-substituted ?,?-unsaturated and ?-lactose ring. The ACGs have gain popularity because they have shown to inhibit the cell growth of cancer cells. The annonaceous acetogenins are known to portray toxicity against cancers cells and slow the effects against the mitochondrial complex I in mammals and insects.
The complex I is responsible for the mitochondrial electron transport system, also known as the NADH: ubiquinone oxidoreductase. Alali et al.(1998) stated ACGs are potent inhibitors of NADH oxidase of the plasma membranes of cancer cells which action is to decrease oxidative and cytosolic ATP production. The deprivation of ATP causes the apoptosis—cell death. Since cancer cells are known to have higher demands of ATP, the A. muricata inhibits the mitochondrial complex I yielding a potential cancer therapy.
Essentially, the A. muricata have been attributed to contain ACGs in all its organism which have shown to be effective against cancers. For example, Qazi et al. (2018), describe the molecular mechanisms A. muricata enclosed in several vitro or vivo studies. When the active compound of ACGs of A.muricata was induce in pancreatic cancer, colon cancer, lung cancer, prostate cancer, and breast cancer studies disclose a positive outcome to cancer cells resistant.
During the surveillance of pancreatic cancer, capsules containing leaf and steam powder of A.muricata reported antiproliferative, antitumor effects and induce downregulation of mucin 4 ( MUC4) a protein known to cause cancer. In another, study using vitro study, lung cancer cell line A549 was extracted and treated with the A.muricata leaf. The treatment revealed A.muricata suppress nuclear factor-kB (NF-kB) which stimulates inflammation by producing apoptosis.
As well caused the cell cycle to arrest at the G0 /G1 phase an important cell cycle mechanism that activates during G1 known as the checkpoint to ensure everything is ready for DNA synthesis, but if cell gets deprive an alteration in gene expression can occur fluctuating its mechanism into cancerous cells. Also, in a prostate cancer research illustrated at low concentration (?1 ?g/ml) of A.muricata pulp can influence the antiproliferative activity in pancreatic cell lines. Moreover, in a vivo study using mouse models A.muricata show to inhibited the growth of MCF-7 breast cancer cells by reducing estrogen receptor, cyclin D1 and antiapoptotic gene Bcl2. As well, exposed to be antiproliferative and antitumor. As a result a chemical structure of two AGEs found to target breast cancer phenotype can be encounter below. The table after provides some anticancer studies on A. muricata and its anticancer effects.
Active compound (SF-1603)
Moreover, a research by Tejasari et al. (2018) investigated the active compound (SF-1603) extracted from the A.muricata leaves in apoptosis induction of liver cancer cell. Let’s recall apoptosis means cells death; its purpose is to remove cells that are unnecessary, unhealthy or that can damage. As well, apoptosis helps to keep processes balanced within the body, as cells ages and make room for new cells. Consequently, apoptosis play an important process in suppressing the progression of liver diseases too much or too little can degenerative disease and cancer. The apoptosis process occurs because extrinsic pathway (death receptors) that activate the caspases 8 and 10 and the intrinsic pathway (mitochondrial pathway) activate the caspase 9. Thus, the activation of these caspases leads to apoptosis.
In this research, a vitro study was used in which HepG2 cell line were derived from a tumor issue of hepatocellular carcinoma (the most common type of liver cancer) suffers and were treated with active compound (SF-1603) extracted from the A. muricata leaves. The study showed that when administering SF-1603 compound at higher doses than the control group the apoptosis process increased. Results can be observed at the graph below. As a result, the active compound (SF-1603) found in the leaves of A. muricata enclose a powerful anticancer ability to induce apoptosis in liver cancer cells (HepG2) cell line cultures.
On the other hand, Moghadamatousi et al. (2014) investigated the anticancer properties of ethyl acetate extract of Annona muricata leave (EEAM) on HT-29 and HCT-116 colon cancer cells. EEAM uncover to arrest the cell cycle of colon cancer cells at G1 phase which stimulate apoptosis in colon cancer cells. As well, reveal that the disruption in the mitochondrial membrane potential (MMP) was caused by excessive accumulation of reactive oxygen species (ROS) in cancer cells inducing mitochondrial mediated apoptosis in colon cancer cells which were associated with the G1 cell cycle. This mechanism can be observed in the figure below.
As mention earlier induction of apoptosis play a crucial role in prevention and suppression of cancer cells, so it thus with breast cancer cells. Daddiouaissa et al. (2019) investigate the vitro effects breast cancer cell had when ionic liquid extract of Graviola fruit (IL-GFE) was placed on MCF-7 breast cancer cells. Results reveal IL-GFE can stimulate anti-proliferative effects against MCF-7 breast cancer cell lines by inducing loss of cell viability via apoptosis, morphology changes, and cell cycle arrest at the G0 / G1 phase (, 2019). As a results, the image below represents how the IL-GFE treatment inhibits MCF-7 breast cancer at several time intervals.
The longer they are expose the more the cell growth seems to reduced. In addition,….. identified, once clinical case in which consumption of boiled leaves of A. muricata in combination with the chemotherapeutic drug has shown to stabilize disease in a 66-year-old woman with breast cancer. According to the research, this woman self-medicated by boiling 10-12 dry leaves of A. muricata for 5-7 minutes and consumed 8 oz daily. As a result her cancer remained stable for five years.
Anticancer mechanism of A. Muricata
The A. muricata has shown to demonstrate to be an efficient candidate herbal remedy to posse anticancer properties. For example, Qazi et al.( 2018) explained ACGs have shown to be an effect metabolism through a down-regulation of mitochondrial NADH oxidase function, inhibiting the mitochondrial complex I of the electron transport chain. As well, A. muricate has demonstrated to have a positive effect on the NF-kB pathway which is associated to have a helpful benefit in the management of cancer by inhibiting the site of inflammation. The depletion of ATP also shows to be another optimistic mechanism A. muricata has on anticancer properties. The detailed molecular mechanisms of A. muricata against cancer can be summarized on the figure below.
Overall, it may be said A. muricata possess a range of biological activities the most promising activities are the anticancer. The A. muricata has shown to have several compounds such as annonaceous acetogenins which are anticancer beneficial. As well, when the ethyl acetate extract of Annona muricate leaves were used in treatment, excessive accumulation of reactive oxygen species disrupting the mitochondrial mediated potential known to cause caners However, continuation of research is required to investigate the use of A. muricata as most recent research involve vitro study and a urge of vivo study is still need.