Oral administration of benzyl-isothiocyanate inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice

Abstract

Benzyl-isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has also been shown to have anti-tumor properties. To evaluate the effects of BITC administration on the tumor growth and metastasis of breast cancer, 4T1 murine mammary carcinoma cells were injected into the inguinal mammary fat pads of syngeneic female BALB/c mice. One day later, the mice were subjected to gavage for 4 weeks with BITC (0, 5, or 10 mg/kg body weight/day). Oral BITC treatment induced a significant reduction in the growth of solid tumors. BITC reduced hemoglobin contents and CD31 and vascular endothelial growth factor (VEGF) expression in the tumors, as well as circulating levels of VEGF. Reduced expressions of proliferating cell nuclear antigen and cyclin-dependent kinase 4 were noted in the tumors of BITC-treated mice. BITC markedly increased the numbers of apoptotic cells with increased Bax expression, cleaved caspase-3, and PARP levels, but reduced Bcl-2 expression in tumor tissues. In addition, BITC was shown to reduce the numbers of pulmonary tumor nodules and the total pulmonary metastatic volume. BITC induced a significant reduction in the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and urokinase-type plasminogen activator in the sera and lungs of 4T1 cell-injected mice. However, the concentrations of TIMP-2 and plasminogen activator inhibitor-1 were increased in the sera and lungs of BITC-treated mice. The results of this study indicate that BITC has potential as a preventive agent for metastatic breast cancer.

Benzyl Isothiocyanate: Double Trouble for Breast Cancer Cells

“…Analysis of the vasculature in tumors of mice with MDA-MB-231 xenografts indicated smaller vessel area after BITC treatment compared with control based on immunohistochemistry for the angiogenesis markers CD31 and VEGF receptor 2 (VEGFR2; 12). The BITC treatment caused a significant reduction in the levels of matrix metalloproteinase (MMP)-2 and MMP-9 and downregulated urokinase-type plasminogen activator and plasminogen activator inhibitor-I in breast cancer cells and xenografts (13). In addition, BITC has been shown to inhibit neovascularization in the rat aorta and chicken chorioallantoic membrane (28), consistent with inhibition of cancer cell migration and invasion.…”

“…BITC-induced apoptosis has been documented in cultured (21,(24)(25)(26) as well as in xenografted cancer cells (13,21). Execution of BITC-induced apoptosis likely depends on both mitochondrial and death receptor pathways (21).…”

“…Dietary administration of BITC for 25 weeks markedly suppressed the incidence and burden of mammary hyperplasia and carcinoma in mammary tumor virus (MMTV)-neu female mice (12). BITC decreased pulmonary metastasis multiplicity and volume of 4T1 murine mammary carcinoma cells injected into the inguinal mammary fat pads of syngeneic female BALB/c mice (13). In addition to the animal studies, a great deal of information exists on in vitro anticarcinogenic effects of BITC in a wide variety of tumor cell lines derived from different organ sites (14).…”

A Novel Cinnamide YLT26 Induces Breast Cancer Cells ApoptosisviaROS-Mitochondrial Apoptotic Pathwayin Vitroand Inhibits Lung Metastasisin Vivo

“…4T1 breast tumor cells had been confirmed to can metastasize to distant organs such as lung [18,25]. Therefore, the therapeutic efficacy of YLT26 against lung metastases was evaluated when mice were sacrificed.…”

Investigation of bioactive compounds with anti-cancer potential in Carica papaya leaves

“…These bioactive compounds act via multiple mechanisms, such as cancer cell signalling, proliferation, apoptosis, migration and invasion, as well as angiogenesis and carcinogen elimination , Zhang, 2004, Thornalley, 2002, Nakamura and Miyoshi, 2006, Wu et al, 2009, Navarro et al, 2011, Wahle et al, 2011, Soobrattee et al, 2006, Tanaka et al, 2012, Van Breemen and Pajkovic, 2008, to exhibit in vitro and in vivo anticancer activities. BG: 12.7 µmol/g seed, < 0.03 µmol/g pulp BITC: 4.6 µmol/g seed, < 0.003 µmol/g pulp (Nakamura et al, 2007) In vivo animal studies in rat, mouse or hamster for inhibitory effect on:  intestinal carcinogenesis (Sugie et al, 1994)  hepatocarcinogenesis (Sugie et al, 1993)  lung tumourigenesis and metastasis (Kim et al, 2011a, Hecht et al, 2000, Hecht et al, 2002  pancreatic carcinogenesis (Kuroiwa et al, 2006)  urinary bladder carcinogenesis (Okazaki et al, 2002)  mammary carcinogenesis (Warin et al, 2009).…”