Chemopreventive and anti‐angiogenic effects of dietary phenethyl isothiocyanate in an N‐methyl nitrosourea‐induced breast cancer animal model

Abstract

The effect of phenethyl isothiocyanate (PEITC), a component of cruciferous vegetables, on the initiation and progression of cancer was investigated in a chemically induced estrogen-dependent breast cancer model. Breast cancer was induced in female Sprague Dawley rats (8 weeks old) by the administration of N-methyl nitrosourea (NMU). Animals were administered 50 or 150 µmol/kg oral PEITC and monitored for tumor appearance for 18 weeks. The PEITC treatment prolonged the tumor-free survival time and decreased the tumor incidence and multiplicity. The time to the first palpable tumor was prolonged from 69 days in the control, to 84 and 88 days in the 50 and 150 µmol/kg PEITC-treated groups. The tumor incidence in the control, 50 µmol/kg, and 150 µmol/kg PEITC-treated groups was 56.6%, 25.0% and 17.2%, while the tumor multiplicity was 1.03, 0.25 and 0.21, respectively. Differences were statistically significant (p < 0.05) from the control, but there were no significant differences between the two dose levels. The intratumoral capillary density decreased from 4.21 ± 0.30 vessels per field in the controls to 2.46 ± 0.25 in the 50 µmol/kg and 2.36 ± 0.23 in the 150 µmol/kg PEITC-treated animals. These studies indicate that supplementation with PEITC prolongs the tumor-free survival, reduces tumor incidence and burden, and is chemoprotective in NMU-induced estrogen-dependent breast cancer in rats. For the first time, it is reported that PEITC has anti-angiogenic effects in a chemically induced breast cancer animal model, representing a potentially significant mechanism contributing to its chemopreventive activity.

Health Functionality of Organosulfides: A Review

“…This study pointed to the supplementation of isothiocyanates for prolonging the tumor-free survival as well as its chemoprevention in the rats. 28 Additionally, these researchers highlighted that this was the first time it had been reported in a scientific study that an isothiocyanate compound, such as those found in cruciferous vegetables, had anti-angiogenic effects in breast cancer-induced animals. Because a compound with anti-angiogenic effects inhibits the growth of blood vessels, this was a significant finding as a method attesting to the chemopreventative activity of isothiocyanates.…”

“…27 In an animal breast cancer study, progress was made in examining the chemopreventative qualities of isothiocyanates. 28 Breast cancer was induced in eight week old female rats. The rats were administered an isothiocyanate compoundand their tumor appearance was monitored over the course of 18 weeks.…”

“…Because a compound with anti-angiogenic effects inhibits the growth of blood vessels, this was a significant finding as a method attesting to the chemopreventative activity of isothiocyanates. 28 Recent research examines the mechanisms of phenethyl isothiocyanate and its anticancer activity …”

Role of dietary bioactive natural products in estrogen receptor-positive breast cancer

“…Phenethyl isothiocyanate, a naturally occurring isothiocyanate found in some cruciferous vegetables, has cancer prevention effects in breast cancer [234, 235]. Phenethyl isothiocyanate has high bioavailability, and it is likely that phenethyl isothiocyanate undergoes modest first-pass metabolism as metabolites of isothiocyanates can be generated by intestinal as well as hepatic enzymes [236].…”

“…[234] revealed that phenethyl isothiocyanate exerts chemopreventive effect on the promotion and/or progression stage of DMBA-induced rat mammary carcinogenesis. In addition, phenethyl isothiocyanate reduced the tumor incidence and tumor burden in the NMU-induced breast cancer animal model [235]. McCune et al .…”