Did you know that more than half of the medicines prescribed today originated from plants? Aspirin – or acetyl salicylic acid – is derived from the bark of the white willow tree. Paclitaxel, which is used to treat several types of cancers, including breast cancer, was first isolated from the bark of the Pacific yew plant. Yet surprisingly, fewer than 20 percent of the plant species that inhabit our earth have been tested for medicinal properties! We’ve got some work to do!
Archaeological evidence indicates that man has been using plants for treating ailments as far back as 60,000 years ago. Written records dating back more than 5,000 years confirm the use of herbal remedies. Many of us self-prescribe a cup of tea to help fight off a cold or a lotion with aloe to soothe a sunburn without giving the science behind it much thought. But what about tackling the bigger problems we face, like cancer or heart disease? Researchers are beginning to understand the pathways of chronic disease onset and advancement. Those in drug discovery are defining the steps in the disease process that are optimal targets for new therapies.
With financial support from the Center for Literature and Medicine, I am working with junior biomedical humanities major Victoria Angelo to begin the search for chemicals produced by plants at the James H. Barrow Field Station that could inhibit the growth of human leukemia (HL60) cells. HL60 cells are pro-myeloid precursors to the myeloid lineage of blood cells that will differentiate into neutrophils and monocytes, two types of white blood cells. If the promyelocytic cells do not differentiate as they should, the cells will continually divide, leading to the malignant state of leukemia.
Current therapy for Acute Myeloid Leukemia (AML) involves the administration of all trans-retinoic acid (a form of Vitamin A) which triggers the cells to terminally differentiate and the chemotherapy drug etoposide to induce cell death. However, cell resistance to treatment remains a concern. My lab is looking not only at terminal differentiation but also at the induction of HL60 apoptosis. Apoptosis is a form of programmed cell death in which the cell intentionally kills itself through a genetically controlled process that does not harm surrounding cells. This is in contrast to necrotic cell death which is caused by chaotic cell injury often resulting in an inflammatory response against neighboring cells. Such a side effect can be very detrimental to the host.
Victoria and I found several plant species at the field station with promising anti-leukemic properties: tulip tree flowers and stem extracts inhibited the proliferation of HL60 cells by 90 percent and 95 percent, respectively. This approximates the inhibition level of the current chemotherapy drug etoposide. When viewed under the confocal fluorescence microscope following treatment, it was apparent that these same extracts triggered the morphological changes in the HL60 nucleus that are associated with apoptosis. A second plant species, wood sorrel, demonstrated more modest toxicity (30 percent inhibition) in initial testing of the leaf. I will use this research in my Molecular and Cell Biology lab courses to encourage students to learn how to work with a mammalian cell line like HL60 and how to design experiments in plant drug discovery, even from plants in our own backyard.