Inositol hexaphosphate and inositol inhibit DMBA-induced rat mammary cancer.
Because inositol hexaphosphate (InsP6) and inositol (Ins), contained in plants and most mammalian cells, have been demonstrated to have anti-cancer and anti-cell proliferative action in several experimental models of carcinogenesis we have examined the effect of InsP6 +/- Ins on DMBA-induced rat mammary tumor model. Starting two weeks prior to induction with DMBA, the drinking water of female Sprague-Dawley rats was supplemented with either: 15 mM InsP6, 15 mM Ins, or 15 mM InsP6 + 15 mM Ins; a control group received no inositol compounds. Animals (49-day-old) were given a single intragastric dose of DMBA (5 mg/rat) in 1 ml of corn oil administered by oral intubation. After 45 weeks of treatment, the animals in all the three treatment regimens showed a significant reduction (P < 0.05) in tumor incidence. Tumor number, multiplicity and tumor burden were also significantly (P < 0.05) reduced by InsP6 +/- Ins. When all the parameters were taken into consideration, the best results were obtained by the combination treatment of InsP6 + Ins. Four additional groups not receiving DMBA, but drinking tap water, InsP6, Ins, or InsP6 + Ins of the same molarity as experimental groups were observed for the duration of the study to monitor for any toxicity following this long-term treatment; no significant toxicity as evaluated by body weight gain, serum and bone mineral levels was detected. We demonstrate that InsP6 +/- Ins reproducibly inhibits experimental mammary carcinoma, therefore having great potential as a chemopreventive and adjuvant therapeutic agent for this disease as well.
Vucenik
I
I
Department of Medical and Research Technology, University of Maryland School of Medicine, Baltimore 21201-1192, USA.
Yang
G Y
GY
Shamsuddin
A M
AM
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007294:Inositol / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D010833:Phytic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016588:Anticarcinogenic Agents; D007294:Inositol; D015127:9,10-Dimethyl-1,2-benzanthracene; D010833:Phytic Acid