Polyketide Natural Products, Acetogenins from Graviola (Annona muricata L), its Biochemical, Cytotoxic Activity and Various Analyses Through Computational and Bio-Programming Methods

Oxidative Medicine and Cellular Longevity

et al. 2018

119

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 212 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. muricata and its constituents on diverse cancer types and disease states, as well as efficacy and safety concerns. It also includes discussion of our current understanding of possible mechanisms of action, with the hope of further stimulating the development of improved and affordable therapies for a variety of ailments.

Section: Botanical Description and Distributionmentioning

confidence: 99%

Anticancer Properties of Graviola (Annona muricata): A Comprehensive Mechanistic Review

Rady

Bloch

Oxidative Medicine and Cellular Longevity

et al. 2018

119

“…Different classes of constituent “annonaceous” metabolites such as acetogenins are believed to play a major role in the anti-cancer properties of graviola on mammalian cells, in addition to many other constituents such as alkaloids, flavonoids, sterols and others [ 28 , 29 , 30 , 31 ]. Studies to date, all in non-skin tumor lines, suggest that the effects of graviola are selective for inhibiting the growth of cancerous cells, with minimal effects on normal cells [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Graviola (Annona muricata) Exerts Anti-Proliferative, Anti-Clonogenic and Pro-Apoptotic Effects in Human Non-Melanoma Skin Cancer UW-BCC1 and A431 Cells In Vitro: Involvement of Hedgehog Signaling

Rady

et al. 2018

IJMS

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: (i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; (ii) induce G0/G1 cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iii) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs.

“…This therapeutic action of graviola might be due to its ability to selectively inhibit cancer. 5,8 Several studies have shown that low-dose radiation (LDR) has the potential to stimulate response to anticancer drugs and reduce side effects by improving therapeutic efficiency through enhancement of different phenomena such as adaptive response and cell-cell communication. 9,10 Additionally, response of the immune system 11,12 and inhibition of metastasis subsequently have been observed with LDR.…”

Section: Introductionmentioning

confidence: 99%

Anticancer and Apoptogenic Effect of Graviola and Low-Dose Radiation in Tumor Xenograft in Mice

et al. 2020

Background: Annona muricata (graviola) has been claimed for its potential against various diseases including cancer. Objective: The present study aimed to investigate the anticancer effect of graviola extract on Ehrlich solid tumor (EST) mice along with or without a low dose of γ radiation (LDR). Methods: Mice were treated with graviola 50 mg/kg body weight orally for 30 days after EST induction and exposed to γ-ray (2 Gy/week for 3 weeks). Cell cycle, CD44, TGF-β, Bcl-2, and annexin V were determined in tumor tissue. Results: The result obtained showed a significant decrease ( P < .05) of tumor size in 28 graviola-treated EST-bearing mice group (EG) or graviola-treated and irradiated EST-30–bearing mice (EGR) groups versus the EST group. The large number of cells in the sub-G0/G1 population and low cell number at S and M phases signify tumor cell apoptosis and inhibition of cell division in EG or EGR groups. Additionally, significant increases in the expression of CD44 and TGF-β were recorded in EST mice as compared with EG or EGR mice. Furthermore, EST mice exhibited a decrease in the apoptotic marker annexin v and increase in antiapoptotic Bcl-2 compared with EG and EGR mice. Conclusion: It could be suggested that graviola exerts its antitumor effect throughout the regulation of the tumor cell cycle as well as inducing apoptotic signals. The combined treatment of graviola and LDR augments their effect on tumor proliferation.