Induction of apoptosis in murine tumors by cyclophosphamide

Abstract

Whereas there have been several recent reports of the induction of apoptosis by chemotherapy agents in cell culture systems, much less is known about the role of this mode of cell death in tumors treated in vivo. We therefore quantitated the proportion of apoptotic cells induced as a function of time and dose in two murine tumors treated with cyclophosphamide in vivo. The two tumors were a mammary adenocarcinoma, MCa-4, and an ovarian adenocarcinoma, OCa-1. The percent apoptosis was scored from stained histological sections of the tumors using a system based on the characteristic features of the apoptotic nuclei. The kinetics of apoptosis development were determined over a 5-day period following treatment of the mice with 200 mg/kg. The percent apoptosis peaked between 10-18 h in both tumors and then slowly declined to background levels by 5 days after treatment. The dose responses showed that even much lower doses, 25 mg/kg, could induce significant apoptosis and that the proportion of apoptotic cells plateaued at doses higher than 100 mg/kg. These results are compared and contrasted with our previous reports on apoptosis induction in these same tumors with ionizing radiation.

Imaging and dosimetry of 99mTc EC annexin V: Preliminary clinical study targeting apoptosis in breast tumors

“…In vivo work has revealed that apoptosis of breast cancer cells rapidly increases to a peak after chemotherapy, and then rapidly declines to baseline levels with an increase in the apoptotic index from 2.5% at baseline to over 20% following treatment (28)(29)(30). These studies suggest that apoptosis may be a significant contributor to treatment-induced cell death.…”

De Novo Ceramide Regulates the Alternative Splicing of Caspase 9 and Bcl-x in A549 Lung Adenocarcinoma Cells

“…More specifically, the differential regulation of apoptosis by isoforms of both Bcl-x and caspase 9 generated via alternative splicing is of importance as overexpression of either caspase 9 or Bcl-x(s) induces apoptosis, whereas overexpression of caspase 9b and Bcl-x(L) has been shown to inhibit apoptosis in response to Fas, tumor necrosis factor ␣, Bax, TRAIL, UV radiation, and Bik (11,12,(75)(76)(77)(78)(79)(80)(81). Moreover, recent reports have demonstrated a role for the alternative splicing of Bcl-x in chemotherapy sensitivity and induction of apoptosis.…”

Methanolic extract of Pereskia bleo (Kunth) DC. (Cactaceae) induces apoptosis in breast carcinoma, T47-D cell line

“…In accordance with these in vitro studies, other studies also provide evidences that chemotherapeutic agents induce apoptotic tumor cell death in vivo. Experimental studies of murine tumors have demonstrated that cis-paltinum, cyclophosphamide and other chemotherapeutic agents induced apoptosis in various tumors in vivo (Meyn et al, 1994(Meyn et al, , 1995. Several clinical studies have also shown that chemotherapy triggers apoptotic cell death in patients undergoing chemotherapy (Gorczyca et al, 1993;Moreira et al, 1995).…”