title: Growth repression in diethylstilbestrol/dimethylbenz[a]anthracene-induced rat mammary gland tumor using Hecate-CGbeta conjugate.
abstract: Recently, we have shown that Hecate-CGbeta conjugate, which is a fusion of the lytic peptide Hecate and a 15-amino acid fragment of the beta-chain of chorionic gonadotropin (CGbeta), selectively destroys mammary gland carcinoma cells that possess luteinizing hormone receptors (LHR) in vitro. We induced mammary gland tumors using combined prenatal exposure to synthetic diethylstilbestrol (DES) and additional postnatal exposure to dimethylbenz[a]anthracene (DMBA). Rats with tumors were equally randomized (10/group) and treated with either sham (control) or 12 mg/kg body wt of either Hecate or Hecate-CGbeta once a week for 3 weeks by tail vein injections. One week after the last injection, rats were killed. Reverse-transcription-nested polymerase chain reaction/Southern blotting revealed alternatively spliced mRNA for LHR in tumor tissues of 5 of 30 females, which was further confirmed by Western blot analysis. The percentage of tumor volume increase was lowest in the group treated with Hecate-CGbeta (45.3 +/- 27.6), compared with Hecate- and sham-treated, control group (324.8 +/- 78.1 and 309.9 +/- 51.2, respectively; P<0.001). Hecate-CGbeta induced a significant decrease in tumor burden compared with controls (9.5 +/- 2.1 mg/g body wt vs. 21.6 +/- 2.9; P<0.01). A smaller reduction in tumor burden was also observed in Hecate-treated females (17.6 +/- 1.6 mg/g body wt vs. 21.6 +/- 2.9; P<0.05). Our results prove the principle that Hecate-CGbeta conjugate is able to repress mammary gland tumor growth, even in tumor tissues that lack or have very low levels of LHR. The mechanism of Hecate-CGbeta conjugate action in repression of DES/DMBA-induced tumor growth needs to be further analyzed to clarify the molecular mechanisms of Hecate-CGbeta conjugate action in vivo.
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-747 Olsztyn, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Zaleska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Waclawik
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bodek
authors.forename: Anna
authors.initials: A
authors.lastname: Zezula-Szpyra
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Li
authors.forename: Tomasz
authors.initials: T
authors.lastname: Janowski
authors.forename: Wiliam H
authors.initials: WH
authors.lastname: Hansel
authors.forename: Nafis A
authors.initials: NA
authors.lastname: Rahman
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ziecik
mesh_terms: D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000378:metabolism*; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D008555:Melitten / Q000031:analogs & derivatives / Q000378:metabolism*; D010053:Ovary / Q000033:anatomy & histology / Q000378:metabolism; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism
chemical_list: D001551:Benz(a)Anthracenes; D002273:Carcinogens; D018997:Chorionic Gonadotropin, beta Subunit, Human; D006728:Hormones; D011974:Receptors, LH; C480619:hecate-chorionic gonadotropin beta-subunit conjugate; D008555:Melitten; D004054:Diethylstilbestrol