Most of the
breast cancer deaths occur when
cancer cells depart from their tumour of origin and spread systemically and colonise distant organs. The present study was to find out whether
punarnavine, the
quinolizidine alkaloid, with already proven antimetastatic effect on spontaneous B16F10 pulmonary
metastasis has got any effect on a drastic organ-specific
breast cancer spread. For the study, we selected a syngenic mouse 4T1 breast tumour model that mimics stage four of human
breast cancer. The metastatic progression of 4T1 to lymph nodes, lungs, and liver was reduced by
punarnavine (40 mg/kg
body weight) administration in BALB/c mice. This was evident from the histopathology of these organs as well as from the reduction in the metastatic cell density of cultured 6-thioguanine-resistant 4T1 cells in the
punarnavine-treated group compared to the control group. There was also a significant (p < 0.0001) inhibition of the primary breast tumour growth in the orthotopic site of induction with a simultaneous increase (p < 0.0001) in the life span of treated animals. The assessment of biochemical parameters such as
hydroxyproline,
hexosamine,
uronic acid,
sialic acid and γ-glutamyl
transferase and the analysis of various
cytokines VEGF, IL-1β, TNF-α and
GM-CSF showed a similar pattern of reduction in
punarnavine (p < 0.0001) treated group compared to the control group. The gene expression study revealed the inhibitory effect of
punarnavine on the major genes MMP-2, MMP-9,
TIMP-1,
TIMP-2 and
VEGF involved in the metastatic process. These findings undeniably proved the potential of this
quinolizidine alkaloid in combating breast tumour development and its progression in the studied murine model.