• cancer-zapping agent discovered in the 1950s as an unexpected result of a research effort to find a cheap plant-derived source for cortisone synthesis
    • cortisone was found to be a potent anti-inflammatory agent in the 1940s, creating a huge demand for it
    • at the time, the only available source for cortisone was from animals, making it mega expensive (a single dose cost $1000 and required bile from 40 slaughtered oxes)
    • eventually Mexican yams (genus Dioscorea) containing diosgenin, a plant steroid that could be converted into cortisone, were identified as an ideal source for inexpensive cortisone production - Mexico subsequently became the primary supplier of cortisone in the 1960s
  • present in the wood, bark, and fruit of Camptotheca acuminata, a deciduous tree found in southern China that has a long history of use in traditional Chinese medicine
  • clinical trials (testing it on humans) in the early 1970s revealed that, although it wrecked terrible havoc upon tumours, it wrecked terrible havoc upon normal tissues as well, leading to all sorts of impressive side effects (neutropenia - loss of white blood cells, thrombocytopenia - loss of platelets, hemorrhagic cystitis - bladder damage that makes you pee blood, and GI upset with severe diarrhea - no further explanation required) that brought it's development as an anticancer drug to an abrupt end
  • in the 1980s, researchers discovered that it acts upon topoisomerase I, a cellular enzyme that normally functions to untangle supercoiled (tangled up) DNA strands
    • topoisomerase I is most active during replication and transcription, as these processes generate excessive supercoiling
    • untangling is accomplished by cutting, unwinding, and then attaching the stands back to together
    • camptothecin binds to topoisomerase I and inhibits it's ability to rejoin the strands that it breaks apart, causing the normally protective enzyme to start busting DNA stands all to pieces, leading to fragmentation of chromosomes and the death of rapidly dividing cells such as cancer cells
  • this lead to the development of less toxic synthetic derivatives including irinotecan (Campto, Camptosar), topotecan (Hycamtin), and 9-aminocamptothecin (9-AC)
    • these have been used to treat ovarian, colon, and small-cell lung cancers
    • intense diarrhea and immunosupression (due to neutropenia) are still significant side effects
History and Use of Dioscorea as a Food and Herbal Medicine
Oberlies NH, Kroll DJ. Camptothecin and taxol: historic achievements in natural products research. J Nat Prod. 2004 Feb;67(2):129-35.
O'Leary J, Muggia FM. Camptothecins: a review of their development and schedules of administration. Eur J Cancer. 1998 Sep;34(10):1500-8.

3 chemically inspired comments:

R2K said...

: )

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CND said...

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