Flax seed oil reduced tumor growth, modulated immune responses and decreased HPV E6 and E7 oncoprotein expression in a murine model of ectopic cervical cancer

被引:28
作者
Deshpande, Rashmi [1 ]
Raina, Prerna [1 ]
Shinde, Kavita [1 ]
Mansara, Prakash [1 ]
Karandikar, Manjiri [2 ]
Kaul-Ghanekar, Ruchika [1 ]
机构
[1] Bharati Vidyapeeth Deemed Be Univ, Interact Res Sch Hlth Affairs IRSHA, Pune Satara Rd, Pune 411043, Maharashtra, India
[2] Bharati Vidyapeeth DTBU Med Coll, Pune Satara Rd, Pune 411043, Maharashtra, India
关键词
Flax oil; Cervical cancer; Papilloma model; Th1/Th2; Lipid peroxidation; ALPHA-LIPOIC ACID; OXIDATIVE STRESS; FATTY-ACIDS; ESTROGEN-RECEPTOR; COLON-CANCER; T-CELLS; CISPLATIN; INTERFERON; LIGNAN; MCF-7;
D O I
10.1016/j.prostaglandins.2019.04.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cervical cancer is the second leading cause of cancer death in women in India. Previously, we have reported that alpha linolenic acid (ALA), induced apoptosis in cervical cancer cell lines and reduced expression of E6 and E7 oncoproteins with simultaneous decrease in Cox2/VEGF/MAP kinase proteins. Here, we investigated the tumor retardation potential of flax oil (FO), rich in ALA, in mouse papilloma model. Flax oil significantly reduced tumor volume and weight in mice compared to the Tumor control (TC) group. Interestingly, compared to cisplatin (Cis) alone, there was slightly enhanced decrease in tumor weight when FO was given together with Cis (Cis + FO). A marked increase in plasma antioxidant levels in mice, and increase in lipid peroxidation in tumors with simultaneous decrease in liver tissues was observed in Cis + FO group compared to either TC or Cis groups. FO and Cis + FO significantly modulated immune response in mice by increasing CD8 alpha and IFN gamma and decreasing IL-4 expression. Interestingly, when given together with cisplatin, flax oil reduced HPV E6 and E7 oncoprotein expression with concomitant increase in the relative mRNA expression of tumor suppressor genes p53 and Rb. Thus, flax oil could be explored for its therapeutic potential in cervical cancer.
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页数:10
相关论文
共 56 条
[1]  
Abouzeinab N. S., 2015, Journal of Pharmacology and Toxicology, V10, P1
[2]  
[Anonymous], 2017, TANTA DENT J
[3]  
[Anonymous], J MOL BIOCH
[4]  
[Anonymous], CANCERS
[5]   IFN-γ Inhibits IL-4-Induced Type 2 Cytokine Expression by CD8 T Cells In Vivo and Modulates the Anti-Tumor Response [J].
Apte, Simon H. ;
Groves, Penny ;
Olver, Stuart ;
Baz, Adriana ;
Doolan, Denise L. ;
Kelso, Anne ;
Kienzle, Norbert .
JOURNAL OF IMMUNOLOGY, 2010, 185 (02) :998-1004
[6]   Cytostatic inhibition of cancer cell growth by lignan secoisolariciresinol diglucoside [J].
Ayella, Allan ;
Lim, Soyoung ;
Jiang, Yu ;
Iwamoto, Takeo ;
Lin, Dingbo ;
Tomich, John ;
Wang, Weiqun .
NUTRITION RESEARCH, 2010, 30 (11) :762-769
[7]   Flaxseed-Derived Enterolactone Is Inversely Associated with Tumor Cell Proliferation in Men with Localized Prostate Cancer [J].
Azrad, Maria ;
Vollmer, Robin T. ;
Madden, John ;
Dewhirst, Mark ;
Polascik, Thomas J. ;
Snyder, Denise C. ;
Ruffin, Mack T. ;
Moul, Judd W. ;
Brenner, Dean E. ;
Demark-Wahnefried, Wendy .
JOURNAL OF MEDICINAL FOOD, 2013, 16 (04) :357-360
[8]   Synthesis of a novel ester of hydroxytyrosol and α-lipoic acid exhibiting an antiproliferative effect on human colon cancer HT-29 cells [J].
Bernini, Roberta ;
Crisante, Fernanda ;
Merendino, Nicolo ;
Molinari, Romina ;
Soldatelli, Maria Chiara ;
Velotti, Francesca .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (01) :439-446
[9]   Dietary flaxseed inhibits human breast cancer growth and metastasis and downregulates expression of insulin-like growth factor and epidermal growth factor receptor [J].
Chen, JM ;
Stavro, PM ;
Thompson, LU .
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 2002, 43 (02) :187-192
[10]   Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer [J].
Cockbain, A. J. ;
Toogood, G. J. ;
Hull, M. A. .
GUT, 2012, 61 (01) :135-149