Abstract
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 significant increase in plasma antioxidant levels in mice; and increase in lipid peroxidation in tumor 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 CD8α and IFNγ and decrease in IL-4 expression. Interestingly, when given together with cisplatin, flax oil significantly 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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Key Points
Cervical cancer is the second leading cause of cancer death in women in India. Alpha linolenic acid (ALA), has induced apoptosis in cervical cancer cell lines and reduced expression of E6 and E7 oncoproteins with simultaneous decrease in Cox2/VEGF/MAP kinase proteins. ALA has been shown to regulate the growth of cervical cancer cell lines (SiHa and HeLa) through regulation of NO release and induction of lipid peroxidation leading to apoptosis through caspase 3 activation. ALA modulated the growth kinetics of the cervical cancer cells and reduced their migration with concomitant decrease in the expression of VEGF, MMP-2, and MMP-9. Proteins. ALA significantly decreased the expression of phosphorylated
p38, pERK1/2, c-JUN, NFκB, and COX2, proteins and reduced the expression of HPV oncoproteins
E6 and E7, resulting into restoration of expression of tumor suppressor proteins, p53 and Rb.
In the present study, the tumor retardation potential of flax oil (FO), rich in ALA, in mouse papilloma model. FO reduced tumor growth in TC1 induced papilloma model. When given as an adjunct with cisplatin (Cis+FO), FO significantly upregulated the gene expression of p53 and Rb with simultaneous decrease in HPV E6 and E7 oncoprotein expression. FO induced immunomodulation by significantly increasing the expression of IFN and CD8with concomitant decrease in IL4 expression in Cis+FO group. FO reduced cisplatin associated side effects in mouse papilloma model. The results suggest further safety and pharmacokinetic investigations along with clinical trials to establish the potential use of flax oil as an adjunct to conventional therapies.