An interesting development from the study of the precise pharmacomolecular mechanism of natural products is to bring further light to cellular targets and synergis-tical cytotoxic mechanisms. One such study has been carried out by Dassonneville et al. They made a careful study of the cytotoxic effects of cryptolepine from the roots of an Asclepiadaceae Cryptolepis sanguinolenta and showed that the alkaloids intercalate into DNA and interfere with the enzymatic activity of topoisomerase II, inducing cleavage of poly(ADP-ribose) polymerase and the release of cytochrome c from the mitochondria (113).
In regard to the inhibitors of tubulin polymerization, Shi et al. showed that a flavonoid such as 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone from a medicinal Capparaceae of the Asia-Pacific region—Polanisia dodecandra—abrogated the survival of a surprisingly broad array of cancer cell lines, including central nervous system cancer (SF-268, SF-539, SNB-75, U-251), nonsmall-cell lung cancer (HOP-62, NCI-H266, NCI-H460, NCI-H522), small-cell lung cancer (DMS-114), ovarian cancer (OVCAR-3, SK-OV-3), colon cancer (HCT-116), renal cancer (UO-31), a melanoma cell line (SK-MEL-5), and leukemia cell lines (HL-60 [TB], SR), and inhibited tubulin polymerization with an IC50 value of 0.83 (iM (114).
An example of flavonoid of interest is genistein (4'5, 7-trihydroxyisoflavone). Perhaps no other flavonoid has aroused more interest in the field of oncology that genistein, a flavonoid found notably in soybean (Glycine max [L.] Merr, from the family Fabaceae). Genistein has been suggested to lower the incidence of tumor formation, inhibit protein tyrosine skinase activity, and augment the efficacy of radiation for breast and prostate carcinomas, and underwent phase I/II clinical trials. Several biotechnological firms in Japan, Australia, and in the United States manufacture genistein as food supplement in multimillions of US dollars in yearly benefits.
A definitive conclusion regarding the clinical applicability of natural products would seem premature at this time. In fact, the question remains controversial. The hope for a spectacular cancer cure has not materialized, and there are a few cases where natural products alone seem to yield better results than conventional forms of therapy. The use of a logical approach could bring some change to this rather pessimistic picture. Meanwhile, the medicinal plants of the Asia-Pacific region remain in the stage of "potent source of antineoplastic drugs awaiting discovery."
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