# New Achievements for the Treatment of Triple-Negative Breast Cancer
## 3 Novel Approaches to Therapy in TNBC
### Nutraceuticals in the Prevention and Treatment of TNBC
It has been also recently demonstrated that RSV enhanced the in vitro anticancer activity of FL118, a novel camptothecin analogue, in TNBC. Consecutive administration of RSV and FL118 inhibited cell viability in both TNBC MDA-MB-436 and MDA-MB-468 cell lines, also reducing the migratory and invasive capabilities and increasing the number of apoptotic cells [156]. Another natural compound, widely present in onions, apples, grapes, berries, broccoli and other fruits and vegetables, for which anticancer effects have been known for many years, is quercetin [157]; it is also known for its multiple biological activities [158]. Recently, [PERSON] et al. [159] proved the capacity of quercetin to inhibit cytoplasmic HuR protein, an RNA binding protein critical for many disease conditions, and for which elevated levels are associated with TNBC progression and degeneration. Quercetin treatment significantly inhibited cytoplasmic HuR in MDA-MB-231 and MDA-MB-468 TNBC cell lines, decreasing adhesion and migration through the HuR-\(\beta\)-catenin axis and CD44. [PERSON] et al. [160] also demonstrated quercetin's in vitro inhibition of IGF1R activation and its downstream kinases Akt and Erk1/2 in a dose-dependent manner in human MDA-MB-231 cells, suppressing the metastatic phenotype and reducing the expression of EMT transcription factors. Further, in xenograft mouse models, quercetin blocked the growth of MDA-MB-231 tumor xenografts and their lung metastasis, downregulating the expression of specific markers related to invasion (Snail, Slug, fibronectin and vimentin). Olive oil, the consumption of which is connected to a low occurrence of BC, is rich in hydroxytrosol (HT) and oleupopein (OL). Nevertheless, the effects and mechanisms of action of HT and OL in BC cells are still uncertain. A recent study on MDA-MB-231 cell lines showed that treatment with HT or OL reduced MDA-MB-231 cell viability in a dose-dependent manner, and MDA-MB-231 cells were more sensitive to HT than OL treatment. These data suggested that HT and OL may inhibit migration and invasion of TNBC cells by activating autophagy [161]. Another study on OL demonstrated a difference between African American (AA, MDA-MB-468) and Caucasian American (CA, MDA-MB-231) cell lines. OL effectively inhibited cell growth in both cell lines, together with S-phase cell cycle arrest-mediated apoptosis. However, MDA-MB-468 cells were two-fold more sensitive to OL's antiproliferative effect than MDA-MB-231 cells [162]. Fisetin is an important phytoplankton present in vegetables (onions and cucumbers), fruits (persimmon, apples, strawberries), wine and nuts, and possesses antioxidant and anticancer activities. Its effect against MDA-MB-231 cells has been demonstrated [163]. Bitter melon or bitter gourd (_Momordia charantia_) was shown to suppress triple-negative breast cancer cell growth [164], and recently, mango (_Mangifera indica_) extracts were suggested for the treatment of TNBC. _M. indica_ bark and seed extracts significantly halted the growth of MDA-MB-231 cells with IC\({}_{50}\) values of 108 ug/mL and 33 ug/mL, respectively [165]. Pomergnanate (_Punica granatum_ L. Punicaceae) has shown antiproliferative, anti-invasive, and pro-apoptotic activity against MDA-MB-231 cell lines [166]. Moreover, pomergnanate peels, the major byproducts of pomergnanate juice processing, particularly the Akko variety, showed antiproliferative activity towards human BC cell lines [167]. A sea-cucumber (_Holothuria scabra_) extract suppressed the viability of MDA-MB-231 in a dose- and time-dependent manner by enhancing apoptosis, indicated by a marked increase of proapoptotic Bax and pro-caspase three expressions, and decreased expression of anti-apoptotic Bcl-2 [168]. Frankincense, an oleogum resin from trees of the genus _Boswellia_ Roxb. ex Colebr., belonging to the Burseraceae family, has been studied for its antitumor properties. Its extracts, with total contents of boswellic and lupeolic acids > 30%, showed high activity against MDA-MB-231 cells [169].