MATERIALS AND METHODS: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and 500 μg/day) groups of six animals each, and another group (n=6) treated with TAM 100 μg/day at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice.
RESULTS: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups.
CONCLUSIONS: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.
AIM OF THE STUDY: In this study, the effects of F3, lutein and β-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model.
MATERIALS AND METHODS: Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and β-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profile of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM).
RESULTS: Our findings revealed significant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or β-sitosterol (TM-β) as compared with the untreated group (TM). Statistically significant reduction in body weight was observed in TM compared to the NM or treated (TM-F3, TM-L and TM-β) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause significant changes in full blood count values.
CONCLUSION: F3 significantly reduced the total tumor burden and prevented secondary tumor development in metastatic breast cancer without significant toxicities in 4T1-induced mouse mammary carcinoma model. The current study provides further support for therapeutic development of F3 with further pharmacokinetics studies.
AIM OF THE STUDY: To evaluate the immune stimulatory effects of F3 from S. crispus in NMU-induced rat mammary tumor model.
MATERIALS AND METHODS: Immunohistochemistry analysis of cellular immune parameters (CD4+ or CD8+ T cells, CIITA, MHC-II and CD68) was performed on NMU-induced rat mammary tumor nodules, followed by evaluation of the serum level of 34 cytokines using the cytokine antibody array.
RESULTS: Significant increase in MHC-II, CD4+ and CD8+ T cell and CIITA expression by tumor cells was observed in F3-treated rats compared to the tumor control group. F3-treated rats also displayed a significant decrease in the serum level of CCL2 and CD68+ infiltrating macrophages. Serum IFN-γ level in this group was increased by 1.7-fold suggesting enhanced infiltration of T cells, and upregulation of CIITA and MHC-II expression in the tumor cells might be triggered by F3-induced production of IFN-γ.
CONCLUSION: Our findings demonstrated for the first time that a subfraction from S. crispus, F3, is capable of activating the immune system in rats-bearing NMU-induced mammary tumor, which may contribute to the anticancer effects of F3, and additionally support the traditional use of S. crispus leaves to boost the immune system.