Increased mannose 6-phosphate/insulin-like growth factor II receptor and transforming growth factor beta 1 levels during monoterpene-induced regression of mammary tumors.
The monoterpenes represent a potentially new class of breast cancer therapeutic agents. We have shown that d-limonene induces the regression of advanced rat mammary adenocarcinomas. These regressing tumors have an increased cellular concentration of both the mannose-6-phosphate/insulin-like growth factor II receptors and transforming growth factor beta 1. The terpene-induced regression of mammary tumors may result in part from the mitoinhibitory and differentiation properties of active transforming growth factor beta 1. Furthermore, the activation of transforming growth factor beta 1 in these tumors is likely to be facilitated by the increased concentration of the mannose-6-phosphate/insulin-like growth factor II receptors in the mammary tumor cells. Tumors not responding to terpene therapy lacked a rise in the mannose-6-phosphate/insulin-like growth factor II receptor level which may relate to the fact that this gene is hemizygous due to maternal imprinting.
Jirtle
R L
RL
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710.
Haag
J D
JD
Ariazi
E A
EA
Gould
M N
MN
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D053138:Cyclohexenes; D004354:Drug Screening Assays, Antitumor; D005260:Female; D000077222:Limonene; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000737:chemistry* / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017527:Receptor, IGF Type 2 / Q000032:analysis* / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000378:metabolism
D000970:Antineoplastic Agents; D053138:Cyclohexenes; D017527:Receptor, IGF Type 2; D013729:Terpenes; D016212:Transforming Growth Factor beta; D015127:9,10-Dimethyl-1,2-benzanthracene; D000077222:Limonene