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, colo-rectal, 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 review supports an idea of projecting EL as a promising candidate for developing anticancer drug or adjunct dietary supplements and nutraceuticals.
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Key Points
Patients with metastatic tumors in cancer are often unresponsive to existing therapies and strategies to achieve long-term remission than patients with localized cancer. There is a need to develop new therapeutic modalities to treat metastatic cancers. Enterolactone (EL) is a mammalian lignan derived from flaxseed that possesses potent anti-cancer and/or protective properties against different cancers viz. breast, prostate, colo-rectal, lung, ovarian, endometrial, cervical cancers and hepatocellular carcinoma. The anti-cancer effects of EL have been mainly attributed to its anti-proliferative, pro-apoptotic, anti-inflammatory, anti-angiogenic and anti-metastatic activities. In this review, a
reported anti-cancer effects of EL at preclinical as well as clinical level is presented.
About 30 epidemiological studies support a protective role of dietary intake of EL and its plasma/serum/urine concentrations in several cancers. 19 breast cancer, 5 prostate cancer, 3 colorectal cancer, 1 gastric cancer and 1 lung cancer study reported on the protective or inverse association
between EL and risk of respective cancers. About 12 in-vivo animal studies evaluating the anticancer potential of EL was performed by its direct administration. 30 in-vitro cell culture studies have been identified reporting on the anticancer activities of EL on several human cancer cell lines. These studies reported various cellular and molecular mechanisms of EL against novel therapeutic targets in different types of cancers. EL was found to exhibit a host of activities including chemopreventive, antiproliferative, apoptotic, antimetastatic, immunomodulatory, chemosensitizing and radiosensitizing in different human cancer cell lines such as breast cancer, prostate cancer, colon cancer, lung cancer, ovarian cancer, choriocarcinoma, osteosarcoma and monocytic leukemia cell lines.