Mariano Garcia-Arranz, Damian Garcia-Olmo, Luz Vega-Clemente and Maurice Stroun Pages 1401 - 1410 ( 10 )
Background: A DNA-RNA-lipoprotein complex, termed as virtosome, is released spontaneously from healthy human, other mammalian, avian, amphibian and plant cells in a regulated and energy-dependent manner. Studies on human and mouse lymphocytes, hepatocytes, NIH 3T3 cells and mouse tumour cell lines have shown that virtosomes may be acting as inter-cellular messengers. In particular, virtosomes from non-dividing cells blocked 3H-thymidine incorporation into DNA in tumour cell lines.
Objective: Study of the effect of virtosomes on tumors “in vivo” and “in vitro”.
Methods and Results: The present study shows in vitro effects of virtosomes isolated from rat liver, essentially nondividing cell populations, on cultures of healthy smooth muscle cells (SMC), human umbilical vein endothelial cells (HUVEC), human fibroblasts (h-fibroblasts) and mouse embryonic fibroblasts (NIH-3T3) together with two tumour cell lines, human Duke's type B colorectal adenocarcinoma cells (SW480) and human connective tissue fibrosarcoma cells (HT1080). Multiplication of all cell lines was inhibited by the liver virtosomal preparation even with various dilutions of the extract (100 - 0.5%). In an in vivo study, tumours were initiated by subcutaneous injection of 1.0 x 106 DHD/K12-PROb cells in 6 weeks old male BIDX rats. Visible tumours (<1cm) appeared after 3 weeks and lung metastases after 8 weeks (80%). Virtosomes introduced via a tail vein on tumour initiation resulted in a reduction in tumour size and number.
Conclusion: Virtosomal preparation from a non-dividing cell population inhibited cell division, reduced tumour size and partially blocked metastasis.
Non-dividing cell virtosomes, tumour cell replication, tumours, metastasis, mitotic count.
New Therapy Laboratory, Instituto de Investigacion Sanitaria-Fundacion Jimenez Díaz, Avda Reyes Catolicos 2, 28040 Madrid, Surgery Department, Medicine School, Universidad Autonoma de Madrid. C/ Arzobispo Morcillo s/n 28029, Madrid, New Therapy Laboratory, Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz, Avda Reyes Catolicos 2, 28040 Madrid, 6, Pedro Meylan, 1208 Geneva