Introduction
Cancer is a devastating disease for which there is yet no absolute cure. Genetic predisposition and mutations (abnormal changes in the nuclei of cells) caused by chemicals, radiation, hormones, and viruses account for 5-10% and 90-95% of all cancers, respectively. Cancer afflicts almost every part of the human body from the skin to the marrows and is indiscriminate of age. The annual U.S. death toll from cancer is over 555,000 and costs about $156 billion in direct medical, indirect morbidity and mortality expense and losses.

Different approaches are employed in the treatment of cancer, depending on type, site and stage. In situ cancers are surgically removed and followed up with other treatments if metastasized to the lymph nodes and other organs.

Cancer cells grow and multiply rapidly and anticancer drugs (chemotherapy) normally destroy cancer cells by damaging their genetic material, thus stopping their proliferation. Some drugs work better together than alone, hence two or more drugs are often given at the same time. Unfortunately, most anticancer drugs are not selective, thus healthy cells can also be harmed, especially those that divide quickly. Harm to healthy cells causes the side effects. Healthy cells, however, can replicate and re-establish a normal population and size after chemotherapy.

Radiation therapy, also called radiotherapy, is the treatment of cancer and other diseases with ionizing radiation, especially for localized solid tumors, such as cancers of the skin, tongue, brain, breast, or uterine cervix. Radiotherapy can also be used to treat leukemia and lymphoma (cancers of the blood-forming cells and lymphatic system, respectively). Ionizing radiation destroys cells in the area being treated by damaging their genetic material, making it impossible for these cells to continue to grow. Both cancerous and normal cells are also damaged during treatment.

Newer forms of treatment involve angiogenesis inhibition, stimulating the immune system to fight cancer, bone marrow and peripheral stem cell transplantation, and gene and photodynamic therapy.

Possible side effects of cancer treatment include loss of hair, skin irritation, infection, anemia (due to bone marrow depression), temporary change in skin color in the treated area, bleeding (platelet depletion), infections, chemo-induced cancer, and generalized weakness. Other side effects are largely dependent on the area of the body that is treated.

Pawpaw and Cancer
The pawpaw tree is native to the eastern U.S. It is a member of the family Annonacae, which also includes such tropical fruits as the Cherimoya and Guyabana. Pawpaws have been consumed by Native Americans for thousands of years. Eli Lilly and Company sold a liquid extract of its seeds at the end of the 1800’s as an emetic. Thus, it has a history of safe human use and consumption.

Annonaceous acetogenins are complex mixtures of long chain fatty acids derivatives from the extracts of the twigs of the pawpaw tree. Many of the acetogenins have been isolated and characterized, and their numerous health benefits are being explored. Three, bullatacin, asimicin, and trilobacin, have been identified as the most potent, major, bioactive structural types of acetogenins in the paw paw concentrate.

Difficulties with most of the chemotherapeutic drugs emanate from their concurrent eradication of normal healthy cells, including those responsible for immunity.

Tumor cells grow and replicate more rapidly than normal cells. This is because they are better equipped to receive glucose, a good source of energy for fast replication. Also, cancer cells quickly develop a network of blood vessels (angiogenesis) to ensure an efficient supply of nutrients and oxygen. This is partly why cancer patients lose weight; the cancer cells rapidly take up nutrients meant for normal cells.

Furthermore, with chemotherapy cancer cells develop resistance to the drugs, rendering chemotherapy useless and futile after a period of remission. The same principle applies to other diseases that have become drug resistant, such as malaria. The organisms and cancer cells smartly find a way of protecting themselves from the damaging effects of drugs. They generate what is called the ABC transporter superfamily, which transports a variety of substrates including amino acids, sugars, inorganic ions, polysaccharides, peptides, and proteins into the cells. In cancer cells, a member of this superfamily, called the multidrug resistant (MDR) protein, is overexpressed and helps to pump drugs out of the cancer cells, making the cancer cells simultaneously resistant to a variety of drugs. Thus, the cancer cells are protected from the toxic effects of drug combinations.

Annonaceous acetogenins may be good chemotherapeutic agents for cancer. These compounds inhibit mitochondrial and cytoplasmic production of adenosine triphosphate (ATP), which is the major source of energy for the cells and also a precursor of the nucleotides needed to produce DNA and RNA. Annonaceous acetogenins inhibit the enzymes of complex I in the electron transport system in mitochondria. They also inhibit the NADH oxidases found in the plasma membranes of tumor cells. Their net effect is depletion of ATP levels.

Tumor cells, being typically metabolically more active, are more susceptible than normal cells to the effects of the acetogenins. Angiogenesis requires ATP and angiostatin blocks angiogenesis by inhibiting ATP synthase. Thus, ATP depletion helps to block the growth of new vessels to nourish tumors. Tyrosine kinases, which play roles in tumor progression, are also inhibited by ATP depletion.

Annonaceous acetogenins also thwart MDR tumor cells. The protein pumps (glycoproteins), which extrude the drugs from the tumor cells are energized by ATP. Thus, by depleting ATP, the glycoproptein pumps become dysfunctional.

Ongoing studies confirm the benefits of pawpaw extracts in clinical cancer treatments. Pawpaw extracts can be used to inhibit the growth of cancer cells and as effective alternative or supplement to chemotherapeutic agents. Research information suggests that the bioactive compounds in pawpaw will prevent the growth of cancer cells and shrink tumors. A standardized pawpaw extract, Pawpaw Cell-Reg, containing mixtures of annonaceous acetogenins is now available. Research studies also show that pawpaw extracts are antimicrobial, antifungal, and effective against intestinal worms and head lice.

Contraindication
It is not advisable to take Pawpaw with nutritional supplements like CoQ10 and thyroid stimulators, as these supplements enhance mitochondrial complex 1 activities and energy production, respectively. Likewise, antioxidants should not be taken since they block programmed cell deaths (apoptosis) and can reverse the damaging effects of pawpaw on the cancer cells.

Safety/Toxicity
The acetogenins are not mutagenic. Unlike most antitumor drugs, acetogenins do not exert their effects by poisoning DNA; they selectively inhibit ATP production. These results have been confirmed in a recent publication in which two pawpaw acetogenins were found to be antimicrobial but not mutagenic. In other unpublished results (Asta Laboratories), bullatacin was emetic in pigs. This result demonstrated that the acetogenins very likely explain the former use of Eli Lilly’s liquid extract of pawpaw seeds as an emetic preparation. Unpublished report shows that vomiting (emesis) prevented toxicity of pawpaw capsules in dogs. Emesis is a definite safety factor should someone ingest excessive amounts of this supplement either intentionally or unintentionally. Any potential systemic toxic effects are conveniently thwarted by emesis.

A recent study on the island of Guadeloupe suggested that a higher than usual incidence of atypical Parkinsonism there might be caused by the chronic consumption of herbal teas and fruits from the Annonaceae family (Annona muricata and A. squamosa); some of the benzyltetrahydroisoquinoline alkaloids found therein are believed to be neurotoxic and, thus, may be responsible for the Parkinsonism. Such alkaloids are carefully excluded from the annonaceous extracts during manufacture of Pawpaw Cell-Reg.

References