Anticancer potentiality of lignan rich fraction of six Flaxseed cultivars.

Key Findings

Purified hydrolysates from different cultivars of Flaxseed were tested against three different breast cancer cell lines, two ER + (MCF-7& T47D) and one triple negative (MDA-MB231), in addition to a colorectal (HCT-116) and cervix (HELA) cancer cell lines. PFH-G9 hydrolysate showed the most effective cytotoxic activity against HELA, MCF7 and T47D cell lines which could be attributed to its content of SDG. PFH-G9 significantly attenuated MMP-2 and MMP-9 levels in T47D cells although, TAM an estrogen receptor modulator used in ER positive breast cancer patients treatment significantly enhanced MMP-2 and MMP-9 levels in T47D cells.   Cancer usually enhances VEGF expression, increasing its concentration due to tumor aggression and the poor prognosis, hence VEGF is involved in cancer pathology. In the present study, significant decrease in VEGF expression was detected after treatments with PFH-G9 and TAM.   FS and FSM were found to repress the tumor growth. FO, FS, and FSM significantly reduced the expression of Ki-67; a nuclear protein expressed in proliferated cells and is used as cell proliferation marker. Additionally, flaxseed oil was found to reduce MCF-7 tumor growth partially through IGF-1 signaling pathway. The percentage reduction in tumor growth correlated well with estrogen and progesterone status, where FS and FSM significantly repressed the expression of estrogen and progesterone, while FO on reduced the expression of estrogen. In conclusion, the results show antitumor activity of Egyptian flaxseed especially Giza-9 and its dietary formulations that involved apoptotic, antiangiogenic and antimetastatic effects.

ABSTRACT

The objective of our study is to highlight the therapeutic effect and mechanism of action by which purified Flaxseed hydrolysate (PFH) which is a lignan rich fraction exerts its anticancer activity on a human breast cancer cell line (T47D) and in mice bearing tumor. HPLC analysis of PFH of six flaxseed cultivars had shown that PFH of the cultivar Giza 9 (PFH-G9) contains the highest concentration of SDG (81.64 mg/g). The in vitro cytotoxic potentiality of PFH’s of six flaxseed cultivars was screened against a panel of human cancer cell lines. PFH -G9 showed the most significant cytotoxic activity against ER-receptor positive breast cell lines MCF7 and T47D with IC50 13.8 and 15.8 µg/ml, respectively. Moreover, PFH-G9 reduced the expression of the metastasis marker, 1-α, metalloproteinases and vascular endothelial growth factor (VEGF), one of the most potent stimulators of angiogenesis, while it increased the caspase-3 dependent apoptosis. Our study also showed that dietary intake of 10% of Giza 9 Flaxseeds (FS), fixed oil (FSO) or Flax meal (FSM) twice daily for 3 weeks in mice-bearing solid Ehrlich ascites carcinoma (EAC) resulted in reducing the tumor volume, the expression of estrogen, insulin growth factor, progesterone, VEGF and MMP-2, but enhanced expression of caspase-3.