ABSTRACT
Cancer is one of the most devastating diseases, and recently, a variety of natural compounds with preventive effects on cancer developments have been reported. Sulforaphane (SFN) is a potent anti-cancer isothiocyanate originating from Brassica oleracea (broccoli). SFN, mainly metabolized via mercapturic acid pathway, has high bioavailability and absorption. The present reviews mainly discussed the metabolism and absorption of SFN and newly discovered mechanistic understanding recent years for SFN's anti-cancer effects including promoting autophagy, inducing epigenetic modifications, suppressing glycolysis and fat metabolism. Moreover, its inhibitory effects on cancer stem cells and synergetic effects with other anti-cancer agents are also reviewed along with the clinical trials in this realm.
Subject(s)
Brassica , Neoplasms , Humans , Isothiocyanates/pharmacology , Neoplasms/drug therapy , SulfoxidesABSTRACT
Breast cancer stem cell (BCSC) properties are correlated with the malignancy of tumor cells. Sulforaphane (SFN), a natural isothiocyanate, has anti-cancer effects. However, SFN is an oil-like, hydrophobic and unstable substance. To enhance the inhibitory effect of SFN on BCSC-like properties, the mineralized hyaluronic acid-SS-tetradecyl nano-carriers (M-HA-SS-TA) were prepared. The nano-carriers possessed high SFN entrapment rate (92.36%) and drug-loading efficiency (33.64%). The carriers were responsive to the high reducing and mild acidic tumor micro-environment, leading to rapid SFN releasing from SFN-loaded nano-drug (SFN/M-HA-SS-TA). Through the specific recognition of breast cancer cells bearing CD44+ by HA, M-HA-SS-TA nano-carriers showed excellent tumor-targeting ability. Moreover, compared with free SFN, SFN/M-HA-SS-TA showed much stronger inhibition on the BCSC-like properties (invasiveness, self-renewal and tumor growth) both in vitro and in vivo. Together, these results suggested M-HA-SS-TA nano-carriers were promising platforms for tumor-targeted delivery of SFN, enhancing the therapeutic efficacy against BCSC-like properties by SFN.
Subject(s)
Breast Neoplasms/drug therapy , Disulfides/chemistry , Drug Carriers/chemistry , Hyaluronic Acid/analogs & derivatives , Isothiocyanates/therapeutic use , Nanoparticles/chemistry , Sulfoxides/therapeutic use , Animals , Disulfides/chemical synthesis , Disulfides/metabolism , Drug Carriers/chemical synthesis , Drug Carriers/metabolism , Drug Liberation , Female , Glutathione/metabolism , Humans , Hyaluronic Acid/metabolism , Hydrogen-Ion Concentration , Isothiocyanates/chemistry , Mice, Inbred BALB C , Mice, Nude , Nanoparticles/metabolism , Sulfoxides/chemistry , Xenograft Model Antitumor AssaysABSTRACT
Breast cancer is a common malignancy with poor prognosis. Cancer cells are heterogeneous and cancer stem cells (CSCs) are primarily responsible for tumor relapse, treatment-resistance and metastasis, so for breast cancer stem cells (BCSCs). Diets are known to be associated with carcinogenesis. Food-derived polyphenols are able to attenuate the formation and virulence of BCSCs, implying that these compounds and their analogs might be promising agents for preventing breast cancer. In the present review, we summarized the origin and surface markers of BCSCs and possible mechanisms responsible for the inhibitory effects of polyphenols on BCSCs. The suppressive effects of common dietary polyphenols against BCSCs, such as curcumin, epigallocatechin gallate (EGCG) and related polyphenolic compounds were further discussed.
