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.

Earlier we introduced the concept of ‘nanochemoprevention’ i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention. Here, we extended our work and developed polymeric EGCG-encapsulated nanoparticles (NPs) targeted with small molecular entities, able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa), and evaluated their efficacy in preclinical studies. First, we performed a molecular recognition of DCL- and AG-PEGylation on ligand binding on PSMA active site. Next, the biocompatible polymers PLGA-PEG-A were synthesized and used as base to conjugate DCL or AG to obtain the respective copolymers, needed for the preparation of targeted NPs. The resulting EGCG encapsulating NPs led to an enhanced anti-proliferative activity in PCa cell lines compared to the free EGCG. The behavior of EGCG encapsulated in NPs in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor, using EGCG-loaded NPs, with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of target-specific enhanced bioavailability and limited unwanted toxicity, thus leading to a significant potential for probable clinical outcome.

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.

Bioactive compounds extracted from marine organisms showed several biological activities. The present study is an extension of our earlier studies where we assessed the antiproliferative and pro-apoptotic activities of ethanol, methylene chloride, ethyl acetate, acetone, and chloroform crude extracts of sponges: Negombata magnifica (NmE) and Callyspongia siphonella (CsE) against cancer cells. Herein, we are extending our previous findings on both sponge species depending on an alternative methanol extraction method with more advanced molecular biochemical insights as additional proof for anticancer and antimicrobial activity of N. magnifica and C. siphonella. Therefore, sponge specimens were collected during winter 2020 from the Dahab region at the Gulf of Aqaba. Each sponge was macerated with methanol to obtain the crude extracts; NmE and CsE. GC–MS analysis presented a total of 117 chemical compounds; 37 bioactive, 11 represented previously as constituents for a natural organism, and 69 had no biological activities. NmE dose-dependently inhibited the growth of HepG2, MCF-7, and Caco-2 carcinoma cell lines compared to CsE, which unfortunately has no antiproliferative activity against the same cancer cells. NmE was found to induce G0/G1 cell cycle arrest in HepG2 cells with its inhibition for CDK6, Cyclins D1, and E1 in HepG2, MCF-7, and Caco-2 cells. NmE also activated ROS production in HepG2 cells and induced apoptosis in HepG2, MCF-7, and Caco-2 cells via an increase in pro-apoptotic protein Bax, caspase-3, and cleavage PARP, and a decrease in anti-apoptotic protein BCL2. Unlike its anticancer potential, CsE exhibited clear superior results as an antimicrobial agent with a wider range against six microbial strains, whereas NmE showed a positive antibacterial activity against only two strains.