Look what's Hidden in the Pawpaw-Papaw Tree Fruit

Science News, Feb 29, 1992 by Janet Raloff

During World War II, when bananas were scarce, Jerry L. McLaughlin's dad gave him some "Indiana bananas" -- the custard-like fruit of Asimina triloba, better known as the pawpaw tree. Though only about 4 years old at the time, McLaughlin recalls, "I threw up and never forgot them."

A pharmacognosist at Purdue University in West Lafayette, Ind., McLaughlin now searches for plants possessing natural medicinal properties. Based on his unforgettable encounter with the Indiana banana, he focused a few years ago on the pawpaw. After all, he notes, "parmacology is simply toxicology at a lower dose." The result: He reports finding a family of biologically active compounds -- acetogenins -- "that's very good against cancer, and also terrific at killing insects."

A crude extract of pawpaw twigs killed brine shrimp at a concentration of just 0.04 parts per million (ppm)--well below the 70 ppm concentration of strychnine needed to elicit the same effect. One novel acetogenin his team isolated from the pawpaw extract -- asimicin -- also proved lethal to blowfly larvae, two-spotted spider mites, Mexican bean beetles, mosquito larvae, melon aphids, striped cucumber beetles and a nematode. McLaughlin expects that natural asimicin-based pesticides, for which he holds a patent, may be marketed within four or five years.

McLaughlin also subjected brine shrimp to extracts from the pawpaw's relatives. He hit a lode with Annona bullata, a Cuban native closely related to the "custard apple." From this plant he extracted two acetogenins with anticancer prospects. In tests conducted by a major pharmaceutical company, one of those acetogenins -- bullatacin -- proved 1 million times more potent than the common anticancer drug cisplatin in inhibiting the growth of human ovarian tumors transplanted into mice. The National Cancer Institute is currently testing his acetogenins in in vitro trials, he says.

The acetogenins' mode of action differs from that of most anticancer drugs: Rather than killing a cell by scrambling its DNA, they starve the rapidly divinding cells of the ATP that fuels them. As a result, McLaughlin says, "I don't think we'll have to worry about these [acetogenins] ever causing cancer--as some anticancer agents do."

"Nor do we have to rely on Cuba to get bullatacin, the most potent acetogenin," McLaughlin notes. In the March JOURNAL OF NATURAL PRODUCTS, he and his co-workers will announce isolating bullatacin and six other biologically active acetogenins--including a new compound, trilobacin--from the common pawpaw. The report also shows that trilobacin exhibited high levels of growth suppression in cultured cells of some leukemias, small-cell lung cancer, colon cancer, melanoma, ovarian cancer and renal cancer.

If the pawpaw contains so many potentially toxic agents, how can anyone stomach its fruit? In moderation, McLaughlin observes, the ripe fruit can prove quite edible. But his team's assays indicate that unripe fruits "are almost as toxic as the twigs -- really potent." And that makes sense, he suspects, "because nature wanted to discourage animals from eating it and spreading its seeds before the fruit was ripe."