SN-38, A METABOLITE OF THE CAMPTOTHECIN DERIVATIVE CPT-11, POTENTIATES THE CYTOTOXIC EFFECT OF RADIATION IN HUMAN COLON ADENOCARCINOMA CELLS GROWN AS SPHEROIDS
M. Omura et al., SN-38, A METABOLITE OF THE CAMPTOTHECIN DERIVATIVE CPT-11, POTENTIATES THE CYTOTOXIC EFFECT OF RADIATION IN HUMAN COLON ADENOCARCINOMA CELLS GROWN AS SPHEROIDS, Radiotherapy and oncology, 43(2), 1997, pp. 197-201
Citations number
22
Categorie Soggetti
Oncology,"Radiology,Nuclear Medicine & Medical Imaging
Background and purpose: CPT-11 (7-ethyl-10-[4-(1-piperidino)-1-piperid
ino] carbonyloxycamptothecin) is a new semisynthesized derivative of c
amptothecin. SN-38 (7-ethyl-1O-hpdroxycamptothecin), a metabolite of C
PT-11, plays a key role in the action of CPT-11. Materials and methods
: To determine whether SN-38 potentiates the cytotoxic effect of radia
tion, we investigated the interaction of SN-38 and radiation in vitro
in monolayer cultures and multicellular spheroids of HT-29 human colon
adenocarcinoma cells. Results: HT-29 spheroids were more resistant to
both SN-38 and irradiation than monolayer cells. SN-38 at a concentra
tion of 2.5 mu g/ml, which by itself was not cytotoxic, greatly increa
sed the lethal effects of radiation in spheroids, but not in monolayer
cultures. Exposure to SN-38 following irradiation inhibited the poten
tially lethal damage repair (PLDR) in spheroids. It is suggested that
the mechanism of the radiosensitization by SN-38 is due to the PLDR in
hibition. Conclusions: These results indicate that CPT-11 may play a r
ole as radiosensitizer and that a combination of CPT-11 and irradiatio
n could prove to be a particularly effective strategy with which to tr
eat human colon adenocarcinoma. (C) 1997 Elsevier Science Ireland Ltd.