A massive body of evidence has already been presented clearly indicating that the medicinal plants of the Pacific Rim elaborate a broad array of cytotoxic substances. Most of these have been characterized using experimental procedures designed to examine the cytotoxicity of natural products against human tumor cell lines. These procedures involve in vitro screening where the viability of cultured cells after exposure to an extract or a purified substance is measured.
However, one might take the time to think back and to ask if the extensive use of such techniques might not have failed to characterize important lead compounds from plants, and especially medicinal plants. As a matter of fact, a molecule inactive in vitro might, after metabolic transformation in vivo, be effective in abrogating metastasis. The opposite is true, and promising in vitro results have often led to disappointing clinical trials.
In terms of pharmacokinetics, many host factors, such as the route of administration, the metabolism, the catabolism and clearance will considerably determine the antineoplastic success of a drug. One major difficulty with the clinical effectiveness of chemotherapy of neoplastic diseases is the requirement that it kill malignant tumor cells at doses that allow cells in the patient's vital organs to survive so that the recovery can occur. In other words, it is to obtain a reasonably safe therapeutic index favoring introduction into clinical practice.
Ideally, future antineoplastic drug discovery should be based on a more rational, botanical, chemical, and pharmacological approach. A possible way to test the antineoplastic effects of compounds would be to use some semi in vitro-in vivo models. A more rational approach in antineoplastic research, combined with the enormous chemodiversity of flowering plants, will lead to the discovery of several molecules of clinical value.
The ability of natural products to inhibition of topoisomerase and precipitate apop-tosis mentioned in this chapter are two abilities among several others, of which inhibition of microtubule formation, inhibition of DNA polymerase, protein kinases, protein phosphatase and aromatase, and the use of cytokines, interleukins, and tumor necrosis factor and yet uncovered cellular targets.
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