Flaxseed consumption inhibits chemically induced lung tumorigenesis and modulates expression of phase II enzymes and inflammatory cytokines in A/J mice

Shireen Chikara, Sujan Mamidi, Avinash Sreedasyam, Kishore Chittem, Ralph Pietrofesa, Athena Zuppa, Ganesh Moorthy, Neil Dyer, Melpo Christofidou-Solomidou, Katie M. Reindl

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Abstract

Flaxseed consumption is associated with reduced oxidative stress and inflammation in lung injury models and has shown anticancer effects for breast and prostate tissues. However, the chemopreventive potential of flaxseed remains unexplored for lung cancer. In this study, we investigated the effect of flaxseed on tobacco smoke carcinogen (NNK)-induced lung tumorigenesis in an A/J mouse model. Mice exposed to NNKwere fed a control diet or a 10% flaxseed-supplemented diet for 26 weeks. Flaxseed-fed mice showed reduced lung tumor incidence (78%) and multiplicity, with an average of 2.7 ± 2.3 surface lung tumor nodules and 1.0 ± 0.9 H&E cross-section nodules per lung compared with the control group, which had 100% tumor incidence and an average of 10.2 ± 5.7 surface lung tumor nodules and 3.9 ± 2.6 H&E cross-section nodules per lung. Furthermore, flaxseed-fed mice had a lower incidence of adenocarcinomas compared with control-fed mice. Western blotting performed on normal lung tissues showed flaxseed suppressed phosphorylation (activation) of p-AKT, p-ERK, and p-JNK kinases. RNA-Seq data obtained from normal lung and lung tumors of control and flaxseed-fed mice suggested that flaxseed intake resulted in differential expression of genes involved in inflammation-mediated cytokine signaling (IL1, 6, 8, 9, and 12a), xenobiotic metabolism (several CYPs, GSTs, and UGTs), and signaling pathways (AKT and MAPK) involved in tumor cell proliferation. Together, our results indicate that dietary flaxseed supplementation may be an effective chemoprevention strategy for chemically induced lung carcinogenesis by altering signaling pathways, inflammation, and oxidative stress.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalCancer Prevention Research
Volume11
Issue number1
DOIs
StatePublished - Jan 2018

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Flax
Carcinogenesis
Cytokines
Lung
Enzymes
Neoplasms
Inflammation
Incidence
Oxidative Stress
MAP Kinase Kinase 4
Diet
Chemoprevention
Lung Injury
Xenobiotics
Dietary Supplements
Smoke
Carcinogens
Tobacco
Prostate
Lung Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Flaxseed consumption inhibits chemically induced lung tumorigenesis and modulates expression of phase II enzymes and inflammatory cytokines in A/J mice. / Chikara, Shireen; Mamidi, Sujan; Sreedasyam, Avinash; Chittem, Kishore; Pietrofesa, Ralph; Zuppa, Athena; Moorthy, Ganesh; Dyer, Neil; Christofidou-Solomidou, Melpo; Reindl, Katie M.

In: Cancer Prevention Research, Vol. 11, No. 1, 01.2018, p. 27-37.

Research output: Contribution to journalArticle

Chikara, S, Mamidi, S, Sreedasyam, A, Chittem, K, Pietrofesa, R, Zuppa, A, Moorthy, G, Dyer, N, Christofidou-Solomidou, M & Reindl, KM 2018, 'Flaxseed consumption inhibits chemically induced lung tumorigenesis and modulates expression of phase II enzymes and inflammatory cytokines in A/J mice', Cancer Prevention Research, vol. 11, no. 1, pp. 27-37. https://doi.org/10.1158/1940-6207.CAPR-17-0119
Chikara, Shireen ; Mamidi, Sujan ; Sreedasyam, Avinash ; Chittem, Kishore ; Pietrofesa, Ralph ; Zuppa, Athena ; Moorthy, Ganesh ; Dyer, Neil ; Christofidou-Solomidou, Melpo ; Reindl, Katie M. / Flaxseed consumption inhibits chemically induced lung tumorigenesis and modulates expression of phase II enzymes and inflammatory cytokines in A/J mice. In: Cancer Prevention Research. 2018 ; Vol. 11, No. 1. pp. 27-37.
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abstract = "Flaxseed consumption is associated with reduced oxidative stress and inflammation in lung injury models and has shown anticancer effects for breast and prostate tissues. However, the chemopreventive potential of flaxseed remains unexplored for lung cancer. In this study, we investigated the effect of flaxseed on tobacco smoke carcinogen (NNK)-induced lung tumorigenesis in an A/J mouse model. Mice exposed to NNKwere fed a control diet or a 10{\%} flaxseed-supplemented diet for 26 weeks. Flaxseed-fed mice showed reduced lung tumor incidence (78{\%}) and multiplicity, with an average of 2.7 ± 2.3 surface lung tumor nodules and 1.0 ± 0.9 H&E cross-section nodules per lung compared with the control group, which had 100{\%} tumor incidence and an average of 10.2 ± 5.7 surface lung tumor nodules and 3.9 ± 2.6 H&E cross-section nodules per lung. Furthermore, flaxseed-fed mice had a lower incidence of adenocarcinomas compared with control-fed mice. Western blotting performed on normal lung tissues showed flaxseed suppressed phosphorylation (activation) of p-AKT, p-ERK, and p-JNK kinases. RNA-Seq data obtained from normal lung and lung tumors of control and flaxseed-fed mice suggested that flaxseed intake resulted in differential expression of genes involved in inflammation-mediated cytokine signaling (IL1, 6, 8, 9, and 12a), xenobiotic metabolism (several CYPs, GSTs, and UGTs), and signaling pathways (AKT and MAPK) involved in tumor cell proliferation. Together, our results indicate that dietary flaxseed supplementation may be an effective chemoprevention strategy for chemically induced lung carcinogenesis by altering signaling pathways, inflammation, and oxidative stress.",
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