Published30 Jul Abstract Graviola Annona muricata is a small deciduous tropical evergreen fruit tree, belonging to the Annonaceae family, and is widely grown and distributed in tropical and subtropical regions around the world. The aerial parts of graviola have several functions: the fruits have been widely used as food confectionaries, while several preparations, especially decoctions of the bark, fruits, leaves, pericarp, seeds, and roots, have been extensively used in traditional medicine to treat multiple ailments including cancers by local communities in tropical Africa and South America. The reported therapeutic benefits of graviola against various human tumors and disease agents in in vitro culture and preclinical animal model systems are typically tested for their ability to specifically target the disease, while exerting little or no effect on normal cell viability. Over phytochemical ingredients have been reported in graviola extracts prepared from different plant parts. The specific bioactive constituents responsible for the major anticancer, antioxidant, anti-inflammatory, antimicrobial, and other health benefits of graviola include different classes of annonaceous acetogenins metabolites and products of the polyketide pathway , alkaloids, flavonoids, sterols, and others. This review summarizes the current understanding of the anticancer effects of A.
|Published (Last):||15 October 2017|
|PDF File Size:||7.49 Mb|
|ePub File Size:||8.87 Mb|
|Price:||Free* [*Free Regsitration Required]|
Corresponding author. Received Feb 7; Accepted Aug This article has been cited by other articles in PMC. Associated Data The data will be accessible by contacting the corresponding author of this study. Abstract Background Annona muricata Linn which comes from Annonaceae family possesses many therapeutic benefits as reported in previous studies and to no surprise, it has been used in many cultures to treat various ailments including headaches, insomnia, and rheumatism to even treating cancer.
However, Annona muricata Linn obtained from different cultivation area does not necessarily offer the same therapeutic effects towards breast cancer in regards to its bioactive compound production.
In this study, anti-proliferative and anti-cancer effects of Annona muricata crude extract AMCE on breast cancer cell lines were evaluated. Then, the in vivo anti-cancer study was conducted where mice were fed with extract after inducing the tumor. At the end of the experiment, histopathology of tumor section, tumor nitric oxide level, tumor malondialdehyde level, clonogenic assay, T cell immunophenotyping, and proteome profiler analysis were performed.
Results Annona muricata crude extract samples exhibited different level of cytotoxicity toward breast cancer cell lines. Furthermore, it decreased the level of nitric oxide and malondialdehyde in tumor while also increased the level of white blood cell, T-cell, and natural killer cell population.
Conclusion The results suggest that, B1 AMCE is a promising candidate for cancer treatment especially in breast cancer and deserves further research as an alternative to conventional drugs while also stressed out the selection of soursop sample which plays a significant role in determining its potential therapeutic effect on cancer.
Electronic supplementary material The online version of this article doi Keywords: Annona muricata Linn, Breast cancer cell line, Potency, Leaf aqueous extract, Apoptosis, Anti-metastatic, Immune systems, Inflammation Background Breast cancer is one of the leading cancer affecting women as over 1 million women worldwide are diagnosed with this disease each year [ 1 ].
Despite the current drugs present that manage to suppress the tumor growth, there is an urgent need to explore alternative strategies to overcome several limitations in treating breast cancer including the metastasis of cancerous cells which is the leading cause of mortality and morbidity, increasing the sensitivity of immune system response, and reducing the inflammation caused by cancer.
Annona muricata Linn which belongs to the Annonaceae family has been used in traditional medicine to treat various ailments including fever, rheumatism, cancer, and also as sedative, insecticide, and immunosuppressive activity [ 2 ]. Intensive research on the chemical composition of the leaves [ 3 ] and seeds [ 4 ] lead to the finding of acetogenin compounds which explains the therapeutic effects it possessed. This molecular structure is a very potent compound against cancer as it deprives the highly energy demanding cancer cells from adenosine triphosphate ATP supply via the disruption of mitochondrial electron transport system, hence resulting in apoptosis [ 6 , 7 ].
The production of secondary metabolites is actually a response by plants to cope with the harsh or ever changing environments. It has been reported that plant of similar species collected from different locations has a varied level of secondary metabolites among them [ 8 ] which indicates that the production of the bioactive compounds in the soursop plant could also vary thus, affecting its potency against cancer cell.
Details of the sampling sites and voucher number of each sample are shown in Additional file 1 : Table S1. All of the 19 samples of old mature Annona muricata leaves were air-dried for a week before being ground to a powder using a grind mill. MTT assay The proliferation of the cells or cell viability was assessed by the 3-[4,5-dimethylthiazolyl]-2,5 diphenyltetrazolium bromide MTT dye reduction as described by Zhi-Dong et al [ 9 ].
The cytotoxic potential of the crude extract samples could be determined from this assay based on the IC50 generated. A hundred microliter of cells at a concentration of 0. The cells were seeded in a 6-well plate at a concentration of 2. The cells were harvested according to the incubation time point and the resulting pellets were resuspended in the binding buffer provided.
Cells were seeded in a 6 well-plate at a concentration of 2. The images were captured with a fluorescence microscope equipped with Nikon camera. Cell cycle assay To further examine the effects of B1 AMCE on the induction of apoptosis, the effects on the cell cycle was tested.
The cells were seeded at a concentration of 2. It was conducted based on the protocol outlined by Chen [ 11 ]. The images appeared on the membranes were later captured with an inverted microscope equipped with a camera Nikon, Japan.
Wound healing assay This assay was done using the method outlined by Liang et al. A concentration of 3. All animals were fully conducted in humane and ethical care and under the regulation of the governing body concerning the animals.
Animal treatment Mice were separated into 3 open-cages defining their respective groups; normal, untreated, and treated where each group bearing 7 mice per cage. Tissue samples like tumors and vital organs which include lung and spleen were harvested and directly used in downward analysis.
The mitotic cells present were counted and compared between the groups. Lung organ was harvested from the untreated and treated group of mice under sterile condition and was chopped into smaller pieces as to avoid the clogging of pipette. The wells were washed by PBS and viewed under microscope. Immunophenotyping assay The effect of B1 AMCE on the level of immune cells population from spleen was investigated by this assay.
The spleens from the mice of all groups were harvested in a sterile condition. The single cell suspension were washed twice with ice-cold PBS and followed by the centrifugation step. Later, the cells were washed with PBS and centrifuged until a clean yellow pellet obtained. The result obtained was compared to MDA standard curve. In place of the nitrite- containing sample, the standards were mixed with the Griess reagent and incubated in a similar manner. The washing steps were followed after removing the streptavidin-fluor from the glass chip.
Later, the glass chip was removed from its tube assembly and rinsed with deionized water. On the other hand, A2 and R2 samples were the least potent as both showed weak activity in inhibiting the proliferation of cancer cells as they have higher IC50 compared to the other ACME samples.
Anti-cancer effect of Annona Muricata Linn Leaves Crude Extract (AMCE) on breast cancer cell line.
Its roots, bark, seed, leaves and pulp have been used in traditional African and South American pharmacopeias to treat a variety of diseases such as arthritis, parasitic infection, hypertension, fever or diabetes. Most notably extracts from several parts of the plant have been reported to be toxic to cell lines models for breast, colorectal, skin, head and neck, lung, liver, pancreatic and prostate cancer. Graviola extracts GE have been shown to affect several cancer-specific metabolic pathways which are key to cancer progression such as glucose metabolism, hypoxia response, oxidative stress, apoptosis and immune response. The present review attempts to summarize how Graviola alters those metabolic pathways.
Take a look at the Recent articles
BACKGROUND: Annona muricata Linn which comes from Annonaceae family possesses many therapeutic benefits as reported in previous studies and to no surprise, it has been used in many cultures to treat various ailments including headaches, insomnia, and rheumatism to even treating cancer. However, Annona muricata Linn obtained from different cultivation area does not necessarily offer the same therapeutic effects towards breast cancer in regards to its bioactive compound production. In this study, anti-proliferative and anti-cancer effects of Annona muricata crude extract AMCE on breast cancer cell lines were evaluated. Then, the in vivo anti-cancer study was conducted where mice were fed with extract after inducing the tumor.