Apigenin and naringenin suppress colon carcinogenesis through the aberrant crypt stage in azoxymethane-treated rats

Tety Leonardi, Jairam K.P. Vanamala, Stella S. Taddeo, Laurie A. Davidson, Mary E. Murphy, Bhimanagouda S. Patil, Naisyin Wang, Raymond J. Carroll, Robert S. Chapkin, Joanne R. Lupton, Nancy D. Turner

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Epidemiological evidence suggests that a diet abundant in fruits and vegetables may protect against colon cancer. Bioactive compounds, including flavonoids and limonoids, have been shown to possess antiproliferative and antitumorigenic effects in various cancer models. This experiment investigated the effects of four citrus flavonoids and one limonoid mixture at the promotion stage of chemically induced colon cancer in rats. Male Sprague-Dawley rats (n = 10 rats/group) were randomly allocated to one of six diets formulated to contain 0.1% apigenin, 0.02% naringenin, 0.1% hesperidin, 0.01% nobiletin, 0.035% limonin glucoside/obacunone glucoside mixture or a control diet (0% flavonoid/limonoid). Rats received experimental diets for 10 weeks and were injected with azoxymethane (15 mg/kg) at weeks 3 and 4. Excised colons were evaluated for aberrant crypt foci (ACF) formation, colonocyte proliferation (proliferating cell nuclear antigen assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (immunoblotting). When compared with the control diet, apigenin lowered the number of high multiplicity ACF (HMACF >4 aberrant crypts/focus) by 57% (P < 0.05), while naringenin lowered both the number of HMACF by 51% (P < 0.05) and the proliferative index by 32% (P < 0.05). Both apigenin and naringenin increased apoptosis of luminal surface colonocytes (78% and 97%, respectively; P < 0.05) when compared with the control diet. Hesperidin, nobiletin and the limonin glucoside/obacunone glucoside mixture did not affect these variables. The colonic mucosal protein levels of iNOS or COX-2 were not different among the six diet groups. The ability of dietary apigenin and naringenin to reduce HMACF, lower proliferation (naringenin only) and increase apoptosis may contribute toward colon cancer prevention. However, these effects were not due to mitigation of iNOS and COX-2 protein levels at the ACF stage of colon cancer.

Original languageEnglish (US)
Pages (from-to)710-717
Number of pages8
JournalExperimental Biology and Medicine
Volume235
Issue number6
DOIs
StatePublished - Jun 1 2010

Fingerprint

Azoxymethane
Apigenin
Nutrition
Rats
Aberrant Crypt Foci
Colon
Carcinogenesis
Diet
Limonins
Colonic Neoplasms
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Flavonoids
Hesperidin
Glucosides
Apoptosis
Assays
DNA Nucleotidylexotransferase
Citrus
Vegetables

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Leonardi, T., Vanamala, J. K. P., Taddeo, S. S., Davidson, L. A., Murphy, M. E., Patil, B. S., ... Turner, N. D. (2010). Apigenin and naringenin suppress colon carcinogenesis through the aberrant crypt stage in azoxymethane-treated rats. Experimental Biology and Medicine, 235(6), 710-717. https://doi.org/10.1258/ebm.2010.009359
Leonardi, Tety ; Vanamala, Jairam K.P. ; Taddeo, Stella S. ; Davidson, Laurie A. ; Murphy, Mary E. ; Patil, Bhimanagouda S. ; Wang, Naisyin ; Carroll, Raymond J. ; Chapkin, Robert S. ; Lupton, Joanne R. ; Turner, Nancy D. / Apigenin and naringenin suppress colon carcinogenesis through the aberrant crypt stage in azoxymethane-treated rats. In: Experimental Biology and Medicine. 2010 ; Vol. 235, No. 6. pp. 710-717.
@article{eeca34df538d4ed4b0583688d9b82450,
title = "Apigenin and naringenin suppress colon carcinogenesis through the aberrant crypt stage in azoxymethane-treated rats",
abstract = "Epidemiological evidence suggests that a diet abundant in fruits and vegetables may protect against colon cancer. Bioactive compounds, including flavonoids and limonoids, have been shown to possess antiproliferative and antitumorigenic effects in various cancer models. This experiment investigated the effects of four citrus flavonoids and one limonoid mixture at the promotion stage of chemically induced colon cancer in rats. Male Sprague-Dawley rats (n = 10 rats/group) were randomly allocated to one of six diets formulated to contain 0.1{\%} apigenin, 0.02{\%} naringenin, 0.1{\%} hesperidin, 0.01{\%} nobiletin, 0.035{\%} limonin glucoside/obacunone glucoside mixture or a control diet (0{\%} flavonoid/limonoid). Rats received experimental diets for 10 weeks and were injected with azoxymethane (15 mg/kg) at weeks 3 and 4. Excised colons were evaluated for aberrant crypt foci (ACF) formation, colonocyte proliferation (proliferating cell nuclear antigen assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (immunoblotting). When compared with the control diet, apigenin lowered the number of high multiplicity ACF (HMACF >4 aberrant crypts/focus) by 57{\%} (P < 0.05), while naringenin lowered both the number of HMACF by 51{\%} (P < 0.05) and the proliferative index by 32{\%} (P < 0.05). Both apigenin and naringenin increased apoptosis of luminal surface colonocytes (78{\%} and 97{\%}, respectively; P < 0.05) when compared with the control diet. Hesperidin, nobiletin and the limonin glucoside/obacunone glucoside mixture did not affect these variables. The colonic mucosal protein levels of iNOS or COX-2 were not different among the six diet groups. The ability of dietary apigenin and naringenin to reduce HMACF, lower proliferation (naringenin only) and increase apoptosis may contribute toward colon cancer prevention. However, these effects were not due to mitigation of iNOS and COX-2 protein levels at the ACF stage of colon cancer.",
author = "Tety Leonardi and Vanamala, {Jairam K.P.} and Taddeo, {Stella S.} and Davidson, {Laurie A.} and Murphy, {Mary E.} and Patil, {Bhimanagouda S.} and Naisyin Wang and Carroll, {Raymond J.} and Chapkin, {Robert S.} and Lupton, {Joanne R.} and Turner, {Nancy D.}",
year = "2010",
month = "6",
day = "1",
doi = "10.1258/ebm.2010.009359",
language = "English (US)",
volume = "235",
pages = "710--717",
journal = "Experimental Biology and Medicine",
issn = "1535-3702",
publisher = "SAGE Publications Ltd",
number = "6",

}

Leonardi, T, Vanamala, JKP, Taddeo, SS, Davidson, LA, Murphy, ME, Patil, BS, Wang, N, Carroll, RJ, Chapkin, RS, Lupton, JR & Turner, ND 2010, 'Apigenin and naringenin suppress colon carcinogenesis through the aberrant crypt stage in azoxymethane-treated rats', Experimental Biology and Medicine, vol. 235, no. 6, pp. 710-717. https://doi.org/10.1258/ebm.2010.009359

Apigenin and naringenin suppress colon carcinogenesis through the aberrant crypt stage in azoxymethane-treated rats. / Leonardi, Tety; Vanamala, Jairam K.P.; Taddeo, Stella S.; Davidson, Laurie A.; Murphy, Mary E.; Patil, Bhimanagouda S.; Wang, Naisyin; Carroll, Raymond J.; Chapkin, Robert S.; Lupton, Joanne R.; Turner, Nancy D.

In: Experimental Biology and Medicine, Vol. 235, No. 6, 01.06.2010, p. 710-717.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apigenin and naringenin suppress colon carcinogenesis through the aberrant crypt stage in azoxymethane-treated rats

AU - Leonardi, Tety

AU - Vanamala, Jairam K.P.

AU - Taddeo, Stella S.

AU - Davidson, Laurie A.

AU - Murphy, Mary E.

AU - Patil, Bhimanagouda S.

AU - Wang, Naisyin

AU - Carroll, Raymond J.

AU - Chapkin, Robert S.

AU - Lupton, Joanne R.

AU - Turner, Nancy D.

PY - 2010/6/1

Y1 - 2010/6/1

N2 - Epidemiological evidence suggests that a diet abundant in fruits and vegetables may protect against colon cancer. Bioactive compounds, including flavonoids and limonoids, have been shown to possess antiproliferative and antitumorigenic effects in various cancer models. This experiment investigated the effects of four citrus flavonoids and one limonoid mixture at the promotion stage of chemically induced colon cancer in rats. Male Sprague-Dawley rats (n = 10 rats/group) were randomly allocated to one of six diets formulated to contain 0.1% apigenin, 0.02% naringenin, 0.1% hesperidin, 0.01% nobiletin, 0.035% limonin glucoside/obacunone glucoside mixture or a control diet (0% flavonoid/limonoid). Rats received experimental diets for 10 weeks and were injected with azoxymethane (15 mg/kg) at weeks 3 and 4. Excised colons were evaluated for aberrant crypt foci (ACF) formation, colonocyte proliferation (proliferating cell nuclear antigen assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (immunoblotting). When compared with the control diet, apigenin lowered the number of high multiplicity ACF (HMACF >4 aberrant crypts/focus) by 57% (P < 0.05), while naringenin lowered both the number of HMACF by 51% (P < 0.05) and the proliferative index by 32% (P < 0.05). Both apigenin and naringenin increased apoptosis of luminal surface colonocytes (78% and 97%, respectively; P < 0.05) when compared with the control diet. Hesperidin, nobiletin and the limonin glucoside/obacunone glucoside mixture did not affect these variables. The colonic mucosal protein levels of iNOS or COX-2 were not different among the six diet groups. The ability of dietary apigenin and naringenin to reduce HMACF, lower proliferation (naringenin only) and increase apoptosis may contribute toward colon cancer prevention. However, these effects were not due to mitigation of iNOS and COX-2 protein levels at the ACF stage of colon cancer.

AB - Epidemiological evidence suggests that a diet abundant in fruits and vegetables may protect against colon cancer. Bioactive compounds, including flavonoids and limonoids, have been shown to possess antiproliferative and antitumorigenic effects in various cancer models. This experiment investigated the effects of four citrus flavonoids and one limonoid mixture at the promotion stage of chemically induced colon cancer in rats. Male Sprague-Dawley rats (n = 10 rats/group) were randomly allocated to one of six diets formulated to contain 0.1% apigenin, 0.02% naringenin, 0.1% hesperidin, 0.01% nobiletin, 0.035% limonin glucoside/obacunone glucoside mixture or a control diet (0% flavonoid/limonoid). Rats received experimental diets for 10 weeks and were injected with azoxymethane (15 mg/kg) at weeks 3 and 4. Excised colons were evaluated for aberrant crypt foci (ACF) formation, colonocyte proliferation (proliferating cell nuclear antigen assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (immunoblotting). When compared with the control diet, apigenin lowered the number of high multiplicity ACF (HMACF >4 aberrant crypts/focus) by 57% (P < 0.05), while naringenin lowered both the number of HMACF by 51% (P < 0.05) and the proliferative index by 32% (P < 0.05). Both apigenin and naringenin increased apoptosis of luminal surface colonocytes (78% and 97%, respectively; P < 0.05) when compared with the control diet. Hesperidin, nobiletin and the limonin glucoside/obacunone glucoside mixture did not affect these variables. The colonic mucosal protein levels of iNOS or COX-2 were not different among the six diet groups. The ability of dietary apigenin and naringenin to reduce HMACF, lower proliferation (naringenin only) and increase apoptosis may contribute toward colon cancer prevention. However, these effects were not due to mitigation of iNOS and COX-2 protein levels at the ACF stage of colon cancer.

UR - http://www.scopus.com/inward/record.url?scp=77953192767&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953192767&partnerID=8YFLogxK

U2 - 10.1258/ebm.2010.009359

DO - 10.1258/ebm.2010.009359

M3 - Article

C2 - 20511675

AN - SCOPUS:77953192767

VL - 235

SP - 710

EP - 717

JO - Experimental Biology and Medicine

JF - Experimental Biology and Medicine

SN - 1535-3702

IS - 6

ER -