Anticancer and antimetastatic potential of enterolactone: Clinical, preclinical and mechanistic perspectives

Abstract

Currently cancer is the second leading cause of death globally and worldwide incidence and mortality rates of all cancers of males and females are rising tremendously. In spite of advances in chemotherapy and radiation, metastasis and recurrence are considered as the major causes of cancer related deaths. Hence there is a mounting need to develop new therapeutic modalities to treat metastasis and recurrence in cancers. A significant amount of substantiation from epidemiological, clinical and laboratory research highlights the importance of diet and nutrition in cancer chemoprevention. Enterolactone (EL) is a bioactive phenolic metabolite known as a mammalian lignan derived from dietary lignans. Here in we review the reported anti-cancer properties of EL at preclinical as well as clinical level. Several in-vivo and in-vitro studies have provided strong evidence that EL exhibits potent anti-cancer and/or protective properties against different cancers including breast, prostate, colorectal, lung, ovarian, endometrial, cervical cancers and hepatocellular carcinoma. Reported laboratory studies indicate a clear role for EL in preventing cancer progression at various stages including cancer cell proliferation, survival, angiogenesis, inflammation and metastasis. In clinical settings, EL has been reported to reduce risk, decrease mortality rate and improve overall survival particularly in breast, prostate, colon, gastric and lung cancer. Further, the in-vitro human cell culture studies provide strong evidence of the anticancer and antimetastatic mechanisms of EL in several cancers. This comprehensive *

Impact of lignans in oilseed mix on gut microbiome composition and enterolignan production in younger healthy and premenopausal women: an in vitro pilot study

“…enterodiol (ED) and enterolactone (EL). Given that EL, more than ED, is able to bind the oestrogen receptor ER-α [6][7][8][9] and modulate endogenous oestrogen levels [10], it would be interesting to investigate the production of enterolignans by premenopausal-related gut microbiota layouts, following a lignan-rich diet. The magnitude of the modulating effects of enterolignans is expected to be determined by the biological level of endogenous oestrogen: enterolignans would exert antagonistic activity with normal oestrogen levels, while acting as weak oestrogens when their levels are low [11].…”

Impact of lignans in oilseed mix on gut microbiome composition and enterolignan production in younger healthy and premenopausal women: an in vitro pilot study

“…Each vessel was inoculated with 5 ml of fresh faecal slurry (1/10 w/v) for both healthy and premenopausal subjects. A known prebiotic compound inulin (Raftilose P95, 95% oligosaccharide, β(2-1)-fructan, of which 60% w/w glucose-fructose, 40% w/w fructose, degree of polymerization, [3][4][5][6][7][8][9][10] serving as a positive control was added to a separate batch-culture vessel. A further vessel was prepared under the same conditions but without the addition of any compound (negative control, Next, with locked taps, 0.5 ml of LC-MS water was added, then drained after 10 min.…”

“…Given that EL, more than ED, is able to bind the oestrogen receptor ER-α [6][7][8][9] and modulate endogenous oestrogen levels [10], it would be interesting to investigate the production of enterolignans by premenopausal-related gut microbiota layouts, following a lignan-rich diet. The magnitude of the modulating effects of enterolignans is expected to be determined by the biological level of endogenous oestrogen: enterolignans would exert antagonistic activity with normal oestrogen levels, while acting as weak oestrogens when their levels are low [11].…”

Impact of lignans in oilseed mix on gut microbiome composition and enterolignan production in younger healthy and premenopausal women: an in vitro study

“…Each vessel was inoculated with 5 ml of fresh faecal slurry (1/10 w/v) for both healthy and premenopausal subjects. A known prebiotic compound inulin (Raftilose P95, 95% oligosaccharide, β(2-1)-fructan, of which 60% w/w glucose-fructose, 40% w/w fructose, degree of polymerization, [3][4][5][6][7][8][9][10] serving as a positive control was added to a separate batch-culture vessel. A further vessel was prepared under the same conditions but without the addition of any compound (negative control, ctr) whereas another vessel was used to add the seed mix.…”

“…enterodiol (ED) and enterolactone (EL). Given that EL, more than ED, is able to ligate the oestrogen receptor ER-α [6][7][8][9] and modulate endogenous oestrogen levels [10], it would be interesting to investigate the production of enterolignans by premenopausal-related gut microbiota layouts, following a lignan-rich diet. The amplitude of the modulating effects of enterolignans is expected to be determined by the biological level of endogenous oestrogen: enterolignans would exert antagonistic activity with normal levels of oestrogen, while acting as weak oestrogens when their levels are low [11].…”