Biology Reference
In-Depth Information
Chapter 19
ALA-Dependent Cancericides
I came to realize that life lived to help others is the only one
that matters and that it is my duty and my highest and best
use as a human. (Adapted from Ben Stein)
19.1 Prologue
In 1978, Dougherty and coworkers observed that upon injection of hematoporphyrin
derivative (HpD), a chemically synthesized porphyrin molecule, into cancerous
tissues the compound accumulated to higher concentrations in malignant tissue than
in normal tissues. This finding constituted the basis for use of porphyrins, specifically
HpD, in photoradiation cancer therapy. The work was summarized later by Dougherty
(Dougherty 1987 ). Photodynamic Therapy (PDT), has concentrated primarily on the
use of hematoporphyrin (Hp) and its derivatives, such as dihydrohematoporphyrin and
commercially available Photofrin I and II, which are patented derivatives of Hp.
When the photodynamic herbicides technology (see Chap. 17 ) was described in
1984 (Rebeiz et al. 1984 ). I received several inquiries from the medical community
about the possibility of developing the technology to kill cancer cells. I responded
by the affirmative since plants (Rebeiz et al. 1984 ), insects (Rebeiz et al. 1988 )and
animals shared the same heme pathway up to protoporphyrin IX (Proto). However due
to involvement with photodynamic herbicide and insecticide development I could not
immediately work on developing that technology.
Then in 1989, Malik et al. investigated the possibility of stimulating endogenous
protoporphyrin production by supplementing the medium of transformed cells with
ALA (Malik et al. 1989 ). The K562 cell line did not synthesize Proto during 4 days of
incubation with ALA in darkness. However, FELC (Friend erythroleukemia cells)
and Bsb (a highly metastic cell line) were sensitive to ALA treatment and
synthesized porphyrins in the dark during 4 days of incubation. Trypan blue
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