Selected studies are summarized on this page, in order to highlight the unique properties of the constituents of Annonaceae, and how they can add substantially to advancing cancer therapy.
The challenge of cancer chemotherapy for several decades has been to minimize or successfully navigate the overlap between killing tumor cells and serious toxicities to the patient. The majority of our most widely used chemotherapeutic agents are cytotoxics, with serious adverse effects on bone marrow, the immune system, heart, nervous system, or rapidly dividing cells in the gut, mucosal surfaces, and hair follicles. Yet for patients with aggressive, life-threatening cancers, the potential benefits of the drugs motivate most patients, with physician guidance, to take these risks.
Scientific evidence suggests that active principles of the Annonaceous species are indeed effective against various cancers, and that historical use and animal toxicity data suggest these beneficial effects may be realized at doses that give a wide “therapeutic index”, as described below.
- The Annonaceous acetogenins have been extensively studied with regard to their effects on different types of tumor cells. They are known to be inhibitors, at effective concentrations, of ATP production in cells, via their inhibitory effects on mitochondrial respiratory complex I (2,7). Cancer cells seem to be very sensitive to these effects, because of their elevated metabolic turnover. But in addition to these, other potential anticancer mechanisms have been uncovered for the acetogenins, including the suppression, at very low concentrations, of the hypoxia-inducible factor-1 (HIF-1), which is a key mediator in the proliferation of a number of tumor cell types (1).
- The fruits of the North American pawpaw (Asimina triloba) are widely consumed in various forms in certain regions of the United States, as are tropical relatives cherimoya (Annona cherimola), sweetsop or sugar apple (Annona squamosa), and graviola or soursop (Annona muricata) in many regions of Central and South America and the West Indies. These fruits are known to contain the anti-cancer acetogenins (10), and the widespread consumption of these fruits are not associated with any acute toxic effects. In addition, various preparations from fruits, leaves, seeds or stems of these plants have been used in adjunct or alternative therapy of different forms of cancer, the treatment of parasitic infections, and other uses (2,7,8,9).
- Several published studies have demonstrated in animal models the efficacy of individual acetogenins or Annona (graviola) or Asimina (pawpaw) extracts against the growth of different types of tumors. These include studies in mouse leukemia models (3), rats with N-methyl-N-nitrosourea induced tumors (4), and in pancreatic (5) and breast (6) cancer mouse models. The anticancer effects are observed at doses which are well tolerated in animals.
- An extract of Asimina triloba containing the active acetogenins has been marketed as a dietary supplement for more than 15 years in the US. Extracts of Annona muricata are likewise widely used in Central and South America.
This promise needs to be critically evaluated in carefully designed clinical trials under an FDA-registered IND, using a well-characterized Asimina preparation. Preclinical safety and formulation studies are required to advance this to clinical testing.
In conclusion, Asimina Triloba lab studies have shown that the plant extracts kill cancer cells that are resistant to chemotherapy. Several cancer patients have used it as a supplement and experienced remarkable improvement and great success. In order for Asimina Triloba to become “The Cancer Medicine,” it must be FDA reviewed and approved.
This is the reason the National Cancer Research Society is asking for your financial help—to get the medical research done and obtain approval. With your generosity, Asimina Triloba can be FDA approved as a cancer medicine within 18 months.
Oscar Rubnerth, President
National Clinical Research Society
- Coothankandaswamy V, Liu Y, Mao SC, Morgan JB, Mahdi F, Jekabsons MB, Nagle DG, Zhou YD. The alternative medicine pawpaw and its acetogenin constituents suppress tumor angiogenesis via the HIF-1/VEGF pathway. J Nat Prod. 2010 May 28;73(5):956-61. doi: 10.1021/np100228d. PMID: 20423107; PMCID: PMC2890309.
- McLaughlin JL. Paw Paw and Cancer: Annonaceous Acetogenins from Discovery to Commercial Products. J. Nat. Prod. 2008, 71, 1311–1321 1311
- Ahammadsahib, K. I.; Hollingworth, R. M.; McGovren, J. P.; Hui, Y.-H.; McLaughlin, J. L. Mode of action of bullatacin: a potent antitumor and pesticidal agent. Life Sci. 1993, 53, 343–348. [Upjohn study bullatacin]
- Cuendet M, Oteham CP, Moon RC, Keller WJ, Peaden PA, Pezzuto JM. Dietary Administration of Asimina triloba. (Paw Paw) Extract Increases Tumor Latency in N.- Methyl-N.-nitrosourea–Treated Rats. Pharm. Biol 2008;46:3–7
- Torres MP, Rachagani S, Purohit V, Pandey P, Joshi S, Moore ED, Johansson SL, Singh PK, Ganti AK, Batra SK. Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer Lett. 2012 Oct 1;323(1):29-40. doi: 10.1016/j.canlet.2012.03.031. Epub 2012 Apr 1. PMID: 22475682; PMCID: PMC3371140.
- Dai Y, Hogan S, Schmelz EM, Ju YH, Canning C, Zhou K. Selective growth inhibition of human breast cancer cells by graviola fruit extract in vitro and in vivo involving downregulation of EGFR expression. Nutr Cancer. 2011; 63:795–801. [PubMed: 21767082]
- Mangal, M., Khan, M. I., & Agarwal, S. M. (2016). Acetogenins as potential anticancer agents. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 16, 138–159. https://doi.org/10.2174/1871520615666150629101827
- Moghadamtousi SZ, Fadaeinasab M, Nikzad S, Mohan G, Ali HM, Kadir HA. Annona muricata (Annonaceae): A Review of Its Traditional Uses, Isolated Acetogenins and Biological Activities. Int. J. Mol. Sci. 2015, 16, 15625-15658; doi:10.3390/ijms160715625 9) Qazi AK, Siddiqui JA, Jahan R, Chaudhary S, Walker LA, Sayed Z, Jones DT, Batra SK, Macha MA. Emerging therapeutic potential of graviola and its constituents in cancers. Carcinogenesis. 2018 Apr 5;39(4):522-533. doi: 10.1093/carcin/bgy024. PMID: 29462271; PMCID: PMC5888937.
- Pomper, K. W., Lowe, J. D., Crabtree, S. B., & Keller, W. (2009). Identification of annonaceous acetogenins in the ripe fruit of the North American pawpaw (Asimina triloba). Journal of Agricultural and Food Chemistry, 57, 8339–8343. https://doi.org/10.1021/jf9018239