Skip to main content
Erschienen in: European Journal of Nutrition 1/2007

01.02.2007 | ORIGINAL CONTRIBUTION

Alpha-tocopheryl succinate (α-TOS) modulates human prostate LNCaP xenograft growth and gene expression in BALB/c nude mice fed two levels of dietary soybean oil

verfasst von: Arpita Basu, PhD, Bruce Grossie, Michael Bennett, Nat Mills, Vicky Imrhan

Erschienen in: European Journal of Nutrition | Ausgabe 1/2007

Einloggen, um Zugang zu erhalten

Abstract

Background

Malignancy of the prostate constitutes a leading cause of cancer-related deaths in America and Europe. Alpha-tocopheryl succinate (α-TOS) has been shown to inhibit human prostate cancer growth in vitro, via several mechanisms, including inhibiting prostate-specific antigen (PSA) and vascular endothelial growth factor (VEGF) expressions. The route of α-TOS administration has a profound effect on its antitumor activity, and few studies have investigated its effects on prostate cancer growth in vivo.

Aim of the Study

The present study tested the hypothesis that α-TOS wil reduce the growth of human prostate LNCaP tumors in mice fed low (7%) and high (20%) levels of dietary soybean oil, compared to the controls receiving vehicle, by modulating PSA and VEGF gene expressions in the tumor tissue.

Methods

BALB/c nude mice (n = 42) were subcutaneously inoculated with 1 × 106 LNCaP cells and assigned to one of four dietary groups; 7% or 20% soybean oil diet with or without α-TOS treatment. Three weeks later, mice received daily intraperitoneal injections of α-TOS (100 mg/kg body weight) in sesame seed oil (SSO) for two weeks; controls received SSO injections. Tumor volumes were recorded weekly. Sera, liver, and tumor tissues were collected at seven weeks for serum PSA, testosterone and α-tocopherol analyses, histopathological examination, and reverse transcription and polymerase chain reaction (RT-PCR) amplification of PSA and VEGF gene fragments in tumors. Relative quantification of gene expression was performed using real-time PCR. P ≤ 0.05 was considered significant.

Results

Intraperitoneal injections of α-TOS caused decreased tumor growth in both groups (7% and 20% fat, P < 0.05), versus controls. α-TOS treatment significantly reduced serum PSA and testosterone levels in comparison to the SSO-treated controls (P < 0.05). Control tumors had a greater degree of angiogenesis than α-TOS tumors, as demonstrated by the greater number of blood-filled vessels. PSA and VEGF mRNA expressions, were also reduced with α-TOS treatment (P < 0.05), revealing the possible molecular mechanisms of growth inhibition of LNCaP xenografts by α-TOS.

Conclusions

Our study shows significant reduction in LNCaP xenograft growth with α-TOS treatment in nude mice fed a low (7%) and high (20%) fat soybean oil diets versus controls. Serum PSA and testosterone, tumor angiogenesis, and PSA and VEGF mRNA expressions were markedly reduced by α-TOS administration, suggesting a possible role of α-TOS as a chemotherapeutic agent in human prostate cancer, and warrants further investigations on the dose and delivery of α-TOS in humans.
Literatur
2.
Zurück zum Zitat Granado de la OS, Saa RC, Quintas VA (2006) Epidemiological situation of prostate cancer in Spain. Actas Urol Esp 30:574–582 Granado de la OS, Saa RC, Quintas VA (2006) Epidemiological situation of prostate cancer in Spain. Actas Urol Esp 30:574–582
3.
Zurück zum Zitat Sogani PC, Whitmore WF (1988) Flutamide and other antiandrogens in the treatment of advanced prostatic carcinoma. Cancer Treat Res 39:131–145 Sogani PC, Whitmore WF (1988) Flutamide and other antiandrogens in the treatment of advanced prostatic carcinoma. Cancer Treat Res 39:131–145
4.
Zurück zum Zitat Willis MS, Wians FH (2003) The role of nutrition in preventing prostate cancer: a review of the proposed mechanism of action of various dietary substances. Clin Chim Acta 330:57–83CrossRef Willis MS, Wians FH (2003) The role of nutrition in preventing prostate cancer: a review of the proposed mechanism of action of various dietary substances. Clin Chim Acta 330:57–83CrossRef
5.
Zurück zum Zitat Ripoll EA, Rama BN, Webber MM (1986) Vitamin E enhances the chemotherapeutic effects of adriamycin on human prostatic carcinoma cells in vitro. J Urol 136:529–531 Ripoll EA, Rama BN, Webber MM (1986) Vitamin E enhances the chemotherapeutic effects of adriamycin on human prostatic carcinoma cells in vitro. J Urol 136:529–531
6.
Zurück zum Zitat Israel K, Yu W, Sanders BG, Kline K (2000) Vitamin E succinate induces apoptosis in human prostate cancer cells: role for Fas in vitamin E succinate-triggered apoptosis. Nutr Cancer 36:90–100CrossRef Israel K, Yu W, Sanders BG, Kline K (2000) Vitamin E succinate induces apoptosis in human prostate cancer cells: role for Fas in vitamin E succinate-triggered apoptosis. Nutr Cancer 36:90–100CrossRef
7.
Zurück zum Zitat Yu A, Somasundar P, Balsubramaniam A, Rose AT, Vona DL (2002) Vitamin E and the Y4 agonist BA-129 decrease prostate cancer growth and production of vascular endothelial growth factor. J Surg Res 105:65–68CrossRef Yu A, Somasundar P, Balsubramaniam A, Rose AT, Vona DL (2002) Vitamin E and the Y4 agonist BA-129 decrease prostate cancer growth and production of vascular endothelial growth factor. J Surg Res 105:65–68CrossRef
8.
Zurück zum Zitat Zhang Y, Ni J, Messing EM, Chang E, Yang CR (2002) Vitamin E succinate inhibits the function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells. Proc Natl Acad Sci USA 99:7408–7413CrossRef Zhang Y, Ni J, Messing EM, Chang E, Yang CR (2002) Vitamin E succinate inhibits the function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells. Proc Natl Acad Sci USA 99:7408–7413CrossRef
9.
Zurück zum Zitat Zhang M, Altuwaijri S, Yeh S (2004) RRR-α-tocopheryl succinate inhibits human prostate cancer cell invasiveness. Oncogene 23:3080–3088CrossRef Zhang M, Altuwaijri S, Yeh S (2004) RRR-α-tocopheryl succinate inhibits human prostate cancer cell invasiveness. Oncogene 23:3080–3088CrossRef
10.
Zurück zum Zitat Zu K, Ip C (2003) Synergy between selenium and vitamin E in apoptosis induction is associated with activation of distinctive initiator caspases in human prostate cancer cells. Cancer Res 63:6988–6995 Zu K, Ip C (2003) Synergy between selenium and vitamin E in apoptosis induction is associated with activation of distinctive initiator caspases in human prostate cancer cells. Cancer Res 63:6988–6995
11.
Zurück zum Zitat Venkateswaran V, Fleshner NE, Sugar LM, Klotz LH (2004) Antioxidants block prostate cancer in Lady transgenic mice. Cancer Res 64:5891–5896CrossRef Venkateswaran V, Fleshner NE, Sugar LM, Klotz LH (2004) Antioxidants block prostate cancer in Lady transgenic mice. Cancer Res 64:5891–5896CrossRef
12.
Zurück zum Zitat Neuzil J (2003) Vitamin E succinate and cancer treatment: a vitamin E prototype for selective antitumor activity. Br J Cancer 89:1822–1826CrossRef Neuzil J (2003) Vitamin E succinate and cancer treatment: a vitamin E prototype for selective antitumor activity. Br J Cancer 89:1822–1826CrossRef
13.
Zurück zum Zitat Malafa MP, Neitzel LT (2000) Vitamin E succinate promotes breast cancer tumor dormancy. J Surg Res 93:163–170CrossRef Malafa MP, Neitzel LT (2000) Vitamin E succinate promotes breast cancer tumor dormancy. J Surg Res 93:163–170CrossRef
14.
Zurück zum Zitat Reeves PG, Nielsen FH, Fahey GC (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951 Reeves PG, Nielsen FH, Fahey GC (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951
15.
Zurück zum Zitat Devaraj S, Jialal I (2000) Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications: the effect of alpha-tocopherol supplementation. Circulation 102:191–196 Devaraj S, Jialal I (2000) Low-density lipoprotein postsecretory modification, monocyte function, and circulating adhesion molecules in type 2 diabetic patients with and without macrovascular complications: the effect of alpha-tocopherol supplementation. Circulation 102:191–196
16.
Zurück zum Zitat Hara A, Radin N (1978) Lipid extraction of tissues with a low-toxicity solvent. Annal Biochem 90:420–426CrossRef Hara A, Radin N (1978) Lipid extraction of tissues with a low-toxicity solvent. Annal Biochem 90:420–426CrossRef
17.
Zurück zum Zitat Edelstein RA, Krane RJ, Babayan RK, Morenas A, Moreland RB (1995) A rapid and simple method for the detection of prostate-specific antigen mRNA in archival tissue specimens using a reverse transcription-polymerase chain reaction assay. Urology 45:597–603CrossRef Edelstein RA, Krane RJ, Babayan RK, Morenas A, Moreland RB (1995) A rapid and simple method for the detection of prostate-specific antigen mRNA in archival tissue specimens using a reverse transcription-polymerase chain reaction assay. Urology 45:597–603CrossRef
18.
Zurück zum Zitat Collado B, Gutierrez-Canas I, Rodriguez-Henche N, Prieto JC, Carmena MJ (2004) Vasoactive intestinal peptide increases vascular endothelial growth factor expression and neuroendocrine differentiation in human prostate cancer LNCaP cells. Regul Pept 119:69–75CrossRef Collado B, Gutierrez-Canas I, Rodriguez-Henche N, Prieto JC, Carmena MJ (2004) Vasoactive intestinal peptide increases vascular endothelial growth factor expression and neuroendocrine differentiation in human prostate cancer LNCaP cells. Regul Pept 119:69–75CrossRef
19.
Zurück zum Zitat Eder IE, Culig Z, Ramoner R, Thurnher M, Putz T (2000) Inhibition of LNCaP prostate cancer cells by means of androgen receptor antisense oligonucleotides. Cancer Gene Ther 7:997–1007CrossRef Eder IE, Culig Z, Ramoner R, Thurnher M, Putz T (2000) Inhibition of LNCaP prostate cancer cells by means of androgen receptor antisense oligonucleotides. Cancer Gene Ther 7:997–1007CrossRef
20.
Zurück zum Zitat Jacklin A, Ratledge C, Welham K, Bilko D, Newton CJ (2003) The sesame seed oil constituent, sesamol, induces growth arrest and apoptosis of cancer and cardiovascular cells. Ann N Y Acad Sci 1010:374–380CrossRef Jacklin A, Ratledge C, Welham K, Bilko D, Newton CJ (2003) The sesame seed oil constituent, sesamol, induces growth arrest and apoptosis of cancer and cardiovascular cells. Ann N Y Acad Sci 1010:374–380CrossRef
21.
Zurück zum Zitat Fleshner N, Fair WR, Huryk R, Heston WDW (1999) Vitamin E inhibits the high-fat diet promoted growth of established human prostate LNCaP tumors in nude mice. J Urol 161:1651–1654CrossRef Fleshner N, Fair WR, Huryk R, Heston WDW (1999) Vitamin E inhibits the high-fat diet promoted growth of established human prostate LNCaP tumors in nude mice. J Urol 161:1651–1654CrossRef
22.
Zurück zum Zitat Mukherjee P, Sotnikov AV, Mangian HJ, Zhou JR, Visek WJ (1999) Energy intake and prostate tumor growth, angiogenesis, and vascular endothelial growth factor expression. J Natl Cancer Inst 91:512–523CrossRef Mukherjee P, Sotnikov AV, Mangian HJ, Zhou JR, Visek WJ (1999) Energy intake and prostate tumor growth, angiogenesis, and vascular endothelial growth factor expression. J Natl Cancer Inst 91:512–523CrossRef
23.
Zurück zum Zitat Wang Y, Corr JG, Thaler HT, Tao Y, Fair WR (1995) Decreased growth of established human prostate LNCaP tumors in nude mice fed on low-fat diet. J Natl Cancer Inst 87:1456–1461CrossRef Wang Y, Corr JG, Thaler HT, Tao Y, Fair WR (1995) Decreased growth of established human prostate LNCaP tumors in nude mice fed on low-fat diet. J Natl Cancer Inst 87:1456–1461CrossRef
24.
Zurück zum Zitat Barnett KT, Fokum FD, Malafa MP (2002) Vitamin E succinate inhibits colon cancer liver metastases. J Surg Res 106:292–298CrossRef Barnett KT, Fokum FD, Malafa MP (2002) Vitamin E succinate inhibits colon cancer liver metastases. J Surg Res 106:292–298CrossRef
25.
Zurück zum Zitat Gilbert VA, Zebrowski EF, Chan AC (1983) Differential effects of mega vitamin E on prostacyclin and thromboxane synthesis in streptozotocin-induced diabetic rats. Horm Metab Res 15:320–325CrossRef Gilbert VA, Zebrowski EF, Chan AC (1983) Differential effects of mega vitamin E on prostacyclin and thromboxane synthesis in streptozotocin-induced diabetic rats. Horm Metab Res 15:320–325CrossRef
26.
Zurück zum Zitat Hartman TJ, Dorgan JF, Virtamo J (1999) Association between serum alpha-tocopherol and serum androgens and estrogens in older men. Nutr Cancer 35:10–15CrossRef Hartman TJ, Dorgan JF, Virtamo J (1999) Association between serum alpha-tocopherol and serum androgens and estrogens in older men. Nutr Cancer 35:10–15CrossRef
27.
Zurück zum Zitat Aronson WJ, Tymchuk CN, Elashoff RM (1999) Decreased growth of human prostate LNCaP tumors in SCID mice fed a low-fat, soy protein diet with isoflavones. Nutr Cancer 35:130–136CrossRef Aronson WJ, Tymchuk CN, Elashoff RM (1999) Decreased growth of human prostate LNCaP tumors in SCID mice fed a low-fat, soy protein diet with isoflavones. Nutr Cancer 35:130–136CrossRef
28.
Zurück zum Zitat Thalmann GN, Sikes RA, Chang SM (1996) Suramin-induced decrease in prostate-specific antigen expression with no effect on tumor growth in the LNCaP model of human prostate cancer. J Natl Cancer Inst 88:794–801CrossRef Thalmann GN, Sikes RA, Chang SM (1996) Suramin-induced decrease in prostate-specific antigen expression with no effect on tumor growth in the LNCaP model of human prostate cancer. J Natl Cancer Inst 88:794–801CrossRef
29.
Zurück zum Zitat Weber T, Lu M, Andera L, Lahm H, Gellert N, Fariss MW, Korinek V, Sattler W, Ucker DS, Terman A, Schroder A, Erl W, Brunk UT, Coffey RJ, Weber C, Neuzil J (2002) Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo. Clin Cancer Res 8:863–869 Weber T, Lu M, Andera L, Lahm H, Gellert N, Fariss MW, Korinek V, Sattler W, Ucker DS, Terman A, Schroder A, Erl W, Brunk UT, Coffey RJ, Weber C, Neuzil J (2002) Vitamin E succinate is a potent novel antineoplastic agent with high selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (Apo2 ligand) in vivo. Clin Cancer Res 8:863–869
Metadaten
Titel
Alpha-tocopheryl succinate (α-TOS) modulates human prostate LNCaP xenograft growth and gene expression in BALB/c nude mice fed two levels of dietary soybean oil
verfasst von
Arpita Basu, PhD
Bruce Grossie
Michael Bennett
Nat Mills
Vicky Imrhan
Publikationsdatum
01.02.2007
Erschienen in
European Journal of Nutrition / Ausgabe 1/2007
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-006-0629-4

Weitere Artikel der Ausgabe 1/2007

European Journal of Nutrition 1/2007 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.