TY - JOUR
T1 - Arsenic trioxide and breast cancer
T2 - Analysis of the apoptotic, differentiative and immunomodulatory effects
AU - Baj, Germano
AU - Arnulfo, Alberto
AU - Deaglio, Silvia
AU - Mallone, Roberto
AU - Vigone, Alessandro
AU - De Cesaris, Maria Grazia
AU - Surico, Nicola
AU - Malavasi, Fabio
AU - Ferrero, Enza
N1 - Funding Information:
This work was supported by grants from AIRC (Italian Association for Cancer Research) (Milano, Italy), Special Project ‘AIDS’ (Istituto Superiore di Sanità, Roma, Italy), and Biotechnology Project (L.95/95) (CNR/MURST, Roma) and MURST (Cofin). The CRT, Compagnia di Sanpaolo and Cariverona Foundations provided valuable financial contributions. We wish to thank Dr Ada Funaro (University of Torino, Italy) and Prof. Emanuele Albano (University of Eastern Piedmont, Italy) for helpful discussions.
PY - 2002
Y1 - 2002
N2 - Arsenic trioxide (As2O3) is used clinically to treat acute promyelocytic leukemia and has activity in vitro against several solid tumour cell lines, where induction of differentiation and apoptosis are the prime effects. To investigate the potential therapeutic application of As2O3 to breast cancer, we analysed the effects of As2O3 on the growth of four human breast cancer cell lines: MCF7, MDA-MB-231, T-47D and BT-20. Cells were cultured in 0.5, 2 and 5 μm As2O3, a range of pharmacologically achievable concentrations of As2O3. At ≥2 μM, As2O3 rapidly induced cell death by apoptosis in MCF7 and MDA-MB-231 while T-47D and BT-20 were partially resistant. At 0.5 μM, As2O3 was subapoptotic but induced features of differentiation consisting in upregulation of ICAM-1 (CD54), a marker of mammary epithelial differentiation, and cell cultures appeared morphologically more organized. Furthermore, we demonstrate by standard cytotoxicity assays that As2O3 treatment can augment breast cancer cell lysis by lymphokine-activated killer cells and demonstrate an important role of the ICAM-1/LFA-1 interaction in this process. This additional activity of As2O3 could translate into improved antitumour immunosurveillance in vivo. In conclusion, As2O3 induced varying degrees of differentiation, apoptosis and lysis in these model cell lines, and may be a promising adjuvant to current treatments of breast cancer by virtue of its triple apoptotic, differentiative and immunomodulatory effects.
AB - Arsenic trioxide (As2O3) is used clinically to treat acute promyelocytic leukemia and has activity in vitro against several solid tumour cell lines, where induction of differentiation and apoptosis are the prime effects. To investigate the potential therapeutic application of As2O3 to breast cancer, we analysed the effects of As2O3 on the growth of four human breast cancer cell lines: MCF7, MDA-MB-231, T-47D and BT-20. Cells were cultured in 0.5, 2 and 5 μm As2O3, a range of pharmacologically achievable concentrations of As2O3. At ≥2 μM, As2O3 rapidly induced cell death by apoptosis in MCF7 and MDA-MB-231 while T-47D and BT-20 were partially resistant. At 0.5 μM, As2O3 was subapoptotic but induced features of differentiation consisting in upregulation of ICAM-1 (CD54), a marker of mammary epithelial differentiation, and cell cultures appeared morphologically more organized. Furthermore, we demonstrate by standard cytotoxicity assays that As2O3 treatment can augment breast cancer cell lysis by lymphokine-activated killer cells and demonstrate an important role of the ICAM-1/LFA-1 interaction in this process. This additional activity of As2O3 could translate into improved antitumour immunosurveillance in vivo. In conclusion, As2O3 induced varying degrees of differentiation, apoptosis and lysis in these model cell lines, and may be a promising adjuvant to current treatments of breast cancer by virtue of its triple apoptotic, differentiative and immunomodulatory effects.
KW - Apoptosis
KW - Arsenic trioxide
KW - Breast
KW - Carcinoma
KW - Differentiation
KW - Immunomodulation
UR - https://www.scopus.com/pages/publications/0035985485
U2 - 10.1023/A:1015272401822
DO - 10.1023/A:1015272401822
M3 - Article
SN - 0167-6806
VL - 73
SP - 61
EP - 73
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -
