Abstract
BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LHRH) on human prostate cancers can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, which consists of superactive doxorubicin derivative 2-pyrrolino doxorubicin (AN-201) linked to carrier [D-Lys 6] LHRH. METHODS. The effects of AN-207 and AN-201 were investigated in DU-145 androgen independent and LuCaP-35 androgen sensitive human prostate cancers xenografted into nude mice. Toxicity was evaluated by survival rates, changes in body weights, and leukocyte counts. LHRH receptors on DU-145 and LuCaP-35 tumors were evaluated by radioreceptor assays and RT-PCR. The effects on apoptosis and cell proliferation were investigated by histology and evaluation of apoptotic oncogenes Bcl-2 and Bax by Western Blot analysis. RESULTS. AN-207 inhibited growth of DU-145 tumors significantly by 75% (P < 0.01) and LuCaP-35 human prostate cancers by 80% (P < 0.01), and was less toxic than AN-201. Receptors for LHRH were expressed on DU-145 and LuCaP-35 tumors. Blockade of LHRH receptors with LHRH agonist Triptorelin nullified the effects of AN-207. Treatment with AN-207, but not with AN-201, decreased Bcl-2/Bax ratio in DU-145 tumors and Bcl-2 in LuCaP-35 tumors indicating an increase in apoptotic activity. AN-207, but not AN-201, decreased cell proliferation in both models. CONCLUSIONS. Targeted chemotherapy with AN-207 could be considered for treatment of advanced prostate cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 200-210 |
| Number of pages | 11 |
| Journal | Prostate |
| Volume | 66 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2006 |
| Externally published | Yes |
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Keywords
- Cytotoxic LH-RH analog
- LH-RH receptor
- Prostate cancer
- Targeted therapy
ASJC Scopus subject areas
- Urology
Cite this
Inhibition of human experimental prostate cancers by a targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207. / Stangelberger, Anton; Schally, Andrew V; Nagy, Attila; Szepeshazi, Karoly; Kanashiro, Celia A.; Halmos, Gabor.
In: Prostate, Vol. 66, No. 2, 01.02.2006, p. 200-210.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of human experimental prostate cancers by a targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207
AU - Stangelberger, Anton
AU - Schally, Andrew V
AU - Nagy, Attila
AU - Szepeshazi, Karoly
AU - Kanashiro, Celia A.
AU - Halmos, Gabor
PY - 2006/2/1
Y1 - 2006/2/1
N2 - BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LHRH) on human prostate cancers can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, which consists of superactive doxorubicin derivative 2-pyrrolino doxorubicin (AN-201) linked to carrier [D-Lys 6] LHRH. METHODS. The effects of AN-207 and AN-201 were investigated in DU-145 androgen independent and LuCaP-35 androgen sensitive human prostate cancers xenografted into nude mice. Toxicity was evaluated by survival rates, changes in body weights, and leukocyte counts. LHRH receptors on DU-145 and LuCaP-35 tumors were evaluated by radioreceptor assays and RT-PCR. The effects on apoptosis and cell proliferation were investigated by histology and evaluation of apoptotic oncogenes Bcl-2 and Bax by Western Blot analysis. RESULTS. AN-207 inhibited growth of DU-145 tumors significantly by 75% (P < 0.01) and LuCaP-35 human prostate cancers by 80% (P < 0.01), and was less toxic than AN-201. Receptors for LHRH were expressed on DU-145 and LuCaP-35 tumors. Blockade of LHRH receptors with LHRH agonist Triptorelin nullified the effects of AN-207. Treatment with AN-207, but not with AN-201, decreased Bcl-2/Bax ratio in DU-145 tumors and Bcl-2 in LuCaP-35 tumors indicating an increase in apoptotic activity. AN-207, but not AN-201, decreased cell proliferation in both models. CONCLUSIONS. Targeted chemotherapy with AN-207 could be considered for treatment of advanced prostate cancer.
AB - BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LHRH) on human prostate cancers can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, which consists of superactive doxorubicin derivative 2-pyrrolino doxorubicin (AN-201) linked to carrier [D-Lys 6] LHRH. METHODS. The effects of AN-207 and AN-201 were investigated in DU-145 androgen independent and LuCaP-35 androgen sensitive human prostate cancers xenografted into nude mice. Toxicity was evaluated by survival rates, changes in body weights, and leukocyte counts. LHRH receptors on DU-145 and LuCaP-35 tumors were evaluated by radioreceptor assays and RT-PCR. The effects on apoptosis and cell proliferation were investigated by histology and evaluation of apoptotic oncogenes Bcl-2 and Bax by Western Blot analysis. RESULTS. AN-207 inhibited growth of DU-145 tumors significantly by 75% (P < 0.01) and LuCaP-35 human prostate cancers by 80% (P < 0.01), and was less toxic than AN-201. Receptors for LHRH were expressed on DU-145 and LuCaP-35 tumors. Blockade of LHRH receptors with LHRH agonist Triptorelin nullified the effects of AN-207. Treatment with AN-207, but not with AN-201, decreased Bcl-2/Bax ratio in DU-145 tumors and Bcl-2 in LuCaP-35 tumors indicating an increase in apoptotic activity. AN-207, but not AN-201, decreased cell proliferation in both models. CONCLUSIONS. Targeted chemotherapy with AN-207 could be considered for treatment of advanced prostate cancer.
KW - Cytotoxic LH-RH analog
KW - LH-RH receptor
KW - Prostate cancer
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=31944437524&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=31944437524&partnerID=8YFLogxK
U2 - 10.1002/pros.20335
DO - 10.1002/pros.20335
M3 - Article
VL - 66
SP - 200
EP - 210
JO - Prostate
JF - Prostate
SN - 0270-4137
IS - 2
ER -