<i>Annona muricata</i> Leaf Extract Triggered Intrinsic Apoptotic Pathway to Attenuate Cancerous Features of Triple Negative Breast Cancer MDA‐MB‐231 Cells

Kim, Jee Young; Dao, Thien T. P.; Song, Keun Bae; Park, Sait Byul; Jang, Hyeri; Park, Min Kyoung; Gan, Soo Ueng; Kim, Yeong Shik

doi:10.1155/2018/7972916

Cited by 31 publications

(22 citation statements)

References 25 publications

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“…The changes in features of precancerous lesion observed in the treatment groups RA, RB and RC suggest emending effect of the A. muricata leaf extracts. This is in tandem with the recent in-vitro studies [44] which indicate the crude extract of Annona muricata alone can be used as an alternative chemotherapy against pancreatic, prostate and breast cancer [45]. The mechanism of action of the leaf extract of the leaf extract on cancer cells implies the disruption of mitochondrial membrane to arrest cells in Go/G1 phase and the induction of apoptosis by down regulating Bcl-2 and Bax proteins.…”

Section: Groupsupporting

confidence: 58%

Analysis of annexin 7 gene of malignant prostatic hyperplasia-induced male wistar rats in the presence ofAnnona muricata

Minari

Chikezie

2019

Journal of Taibah University for Science

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Background: Prostate cancer has become the most common cancer among African-American men and the second leading cause of cancer death in men worldwide. Many anti-malignant agents have been isolated from different plant species with minimal or no side effects thus it holds future promise as a resort as cancer biotherapeutics when compared with other treatment methods including synthetic drugs. Aim: This current investigation was aimed at evaluating the anti-proliferative efficacy of the ethanolic extract of Annonamuricata leaf on annexin 7 gene of malignant prostatic hyperplasia induced male wistar rats. Materials and Methods: Sub-chronic daily oral gavage exposure of the test substances to experimental animals lasted for a period of 28 days. Monosodium glutamate and L-arginine (90:22.5 mg/kg/b.wt) with purity 98% were administered concomitantly to the male wistar rats in various treatment groups. A total of 25 male wistar rats of about 6 weeks old weighing between 250-282 grams were used for this investigation. Quantitative and qualitative phytochemicals screening of ethanolic extract of Annona muricata leaf were also carried out. Hematoxylin and eosin staining were used in the histological assay of the prostate tissues. The prostate specific antigen (PSA) values were determined using standard protocol and polymerase chain reaction (PCR) was used to amplify annexin-7 gene. 1.5% agarose gel was used to separate the amplicons into bands of varying patterns. Result: Qualitative analysis demonstrated the presence of alkaloids, Saponins, flavonoids, tannins, cardiac glycoside, reducing sugar, phenol and triterpenes. Quantitative screening of the extract unveiled that alkaloid was present in the highest amount while Cardiac glycosides had the least concentration. The prostate histological assessment revealed a dose-dependent disruption in normal prostate tissue architecture. There was statistically significant difference P ≤ 0.05 in the body weight and prostate specific antigen (PSA) values of the male wistar rats in the experimental groups during the period of this investigation. The varying amplicon band patterns obtained from the treatment groups indicates possible MSG and L-ARG induced mutation in annexin 7 gene. The DNA amplicon bands observed in the positive control without treatments had some degree of similarity with bands obtained from the amplicons in the various treatment groups that were administered with both carcinogens and ethanolic leaf extract while thin bands were observed for the negative control group that was administered with carcinogens alone. Conclusion: This investigation has demonstrated that ethanolic extract of A. muricata leaf could be used as a potent ethno-chemopreventive agent against L-arginine and monosodium glutamate induced malignant prostatic hyperplasia in male wistar rats.

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Section: Groupsupporting

confidence: 58%

Analysis of annexin 7 gene of malignant prostatic hyperplasia-induced male wistar rats in the presence ofAnnona muricata

Minari

Chikezie

2019

Journal of Taibah University for Science

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“…A. squamosa chloroform seed extract also showed antitumor and pro-apoptotic effects on murine and human tumor cells through the induction of Reactive Oxygen Species (ROS) [15]. A. muricata ethyl acetate leaf extract exhibited a mitochondrial-mediated apoptosis on colon cancer cell lines [16] in vitro, on pancreatic cancer cells [17] in vitro and in vivo, and on breast cancer cell lines [18, 19] by upregulating Bax, p53 and downregulating Bcl-2 proteins. In addition, ethanolic and aqueous extracts from leaves, twigs and roots of A. muricata showed a strong anti-proliferative potential and pro-apoptotic effect through G0/G1 cycle arrest [20, 21].…”

Section: Introductionmentioning

confidence: 99%

The pro-apoptotic effect of a Terpene-rich Annona cherimola leaf extract on leukemic cell lines

Ammoury

Younes

Khoury

et al. 2019

BMC Complement Altern Med

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BackgroundThe edible fruit Annona cherimola has previously shown many nutritional and medicinal properties. The current study evaluates the anti-cancer and anti-proliferative properties of Annona cherimola ethanolic leaf extract (AELE) on Acute Myeloid Leukemia (AML) cell lines cultured in vitro (Monomac-1 and KG-1).MethodsThe anti-proliferative effect of A. cherimola ethanolic leaf extract was evaluated via cell viability assay. Its pro-apoptotic effect was assessed through Cell Death ELISA and dual Annexin V/PI staining. To further investigate the molecular mechanism by which the extract promoted apoptosis and inhibited the proliferation of the AML cells used, apoptotic protein expression was determined through western blots. Extract composition was elucidated by Gas Chromatography-Mass Spectrometry (GC-MS).ResultsOur results showed that the treatment with A. cherimola ethanolic leaf extract exhibited an inhibitory effect on the proliferation of both cancer cell lines used in a dose- and time-dependent manner, with no toxic effects on normal mononuclear cells (MNCs) isolated from human bone marrow. This effect was mediated by DNA fragmentation and apoptosis, as revealed by Cell Death ELISA and dual Annexin V/PI staining. Western blot analysis revealed a Bax/Bcl2 dependent mechanism of apoptosis, as well as PARP cleavage, confirming the apoptotic results observed previously. These effects may be attributed to the presence of terpenes which constitute a large component of the leafy extract, as revealed via GC-MS.ConclusionAll the data presented in our study show that the terpene-rich A. cherimola ethanolic leaf extract exhibits an anti-proliferative and pro-apoptotic effect on the AML cell lines used.

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“…Another significant contribution was the work of McLaughlin (2008), demonstrating the participation of AG of graviola in tumor cytotoxicity through inhibition of the mitochondrial complex, which is involved in oxidative phosphorylation and ATP synthesis. According to the study by Kim (2018), the crude extract of graviola leaves induces apoptosis via the mitochondrial pathway and ceases cell proliferation, as well as reducing invasive capacity in breast tumor cells in a dose-dependent manner (Kim et al 2018).…”

Section: Resultsmentioning

confidence: 99%

Phytochemistry and anticancer potential of graviola (Annona muricata)

Viegas

Santos

Costa

2018

Proceedings of MOL2NET 2018, International Conference on Multidisciplinary Sciences, 4th Edition

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Cancer is an invasive proliferative disease that is ranked among death leaders worldwide. There is a need in prospecting for novel therapeutic molecules, as well as the formulation of more effective chemotherapeutics. Since more than 40% of antineoplastics are derivative from natural products, the latter and their synthetic analogues have been widely used in this process, starting from simple to complex molecules, promoting specific target molecule targeting. The use of folk medicine helped in the discovery of a class with anticancer potential: acetogenin (AG). AG belong to the class of polyketides, present in the family Annonaceae. Thus, the objective of the present study was to carry out a review of prospective literature on the use of graviola (Annona muricata) with antitumor activity and future perspectives as chemotherapeutic. The review was conducted through the Medline/PubMed and Science Direct databases, selecting scientific articles on the subject, characterizing the literature review. The graviola has a quantity greater than 70 acetogenins (AG) that are distributed in the stem, leaves and seeds. AG has been shown to participate in the process of inducing death in tumor cells resistant to other chemotherapeutic agents. Many AG derivatives have shown toxicity against cancer cells, including multiple drug resistant (MDR) strains. Bullatacin, another type of AG, also showed marked antitumor activity against mammary cells with multiple drug resistance (MDR) phenotype. Another significant work demonstrated the participation of graviola AG in tumor cytotoxicity through inhibition of the mitochondrial complex, which is involved in oxidative phosphorylation and ATP synthesis. Furthermore, AG promotes apoptosis of breast tumor cells. Thus, the pharmaceutical technology in the formulation of AG as a chemotherapeutic reveals a promising future in cancer treatment, especially the types that present the MDR phenotype, the biggest obstacle in cancer treatment.

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Annona muricata Leaf Extract Triggered Intrinsic Apoptotic Pathway to Attenuate Cancerous Features of Triple Negative Breast Cancer MDA‐MB‐231 Cells

Cited by 31 publications

References 25 publications

Analysis of annexin 7 gene of malignant prostatic hyperplasia-induced male wistar rats in the presence ofAnnona muricata

Analysis of annexin 7 gene of malignant prostatic hyperplasia-induced male wistar rats in the presence ofAnnona muricata

The pro-apoptotic effect of a Terpene-rich Annona cherimola leaf extract on leukemic cell lines

Phytochemistry and anticancer potential of graviola (Annona muricata)

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