**6.2. Breast cancer**

**5.5. Prostate cancer**

82 Phytochemicals - Source of Antioxidants and Role in Disease Prevention

**5.6. Leukemia**

**6.** *In vitro* **studies**

**6.1. Colon cancer**

Prostate cancer is the most common malignancy in men and affects most men over the age of 50 and also presents one of the main causes of mortality. For the *in vivo* study, athymic nude mice are used. To highlight the effects of anthocyanins on tumor growth *in vivo*, DH145 tumor xenograft have been established in these mice. The group of animals treated with anthocyanins received an oral dose of 8 mg/kg per day. The effects of treatment were analyzed every 4 weeks. In the first 4 weeks after incubation, the difference between the control and the treated group was insignificant. In the second set of analyses (8 weeks), the difference between the groups was very clear, the control group tumors being much bigger. These differences were observed until the end of the experiment, demonstrating the ability of anthocyanins to reduce tumor growth [74]. Another study has found that delphinidin is effective *in vitro* on PC3 cells and has determined whether these results are also visible in *in vivo* models. The delphinidin doses were not toxic to the animals because they did not lose weight and did not affect the amount of food they consumed. After measurements for 12 weeks, the differences between the tumors of the two groups (control and treated) each week were significant, suggesting an antiangiogenic effect on tumor cells. At the end of the experiment, tumors were extirpated and

Acute myeloid leukemia is a hematological malignancy that has numerous causes such as chromosomal abnormalities and various gene mutations. Fifty years ago, this type of cancer was incurable, but now around 35–40% of the cases is treatable [85]. Mice Balc/c has been used to identify *in vivo* benefits of mulberry anthocyanins. Leukemia mice treated with anthocyanins had a higher survival rate than the untreated ones, this survival being correlated with the concentration of treatment. All leukemia-induced mice had the spleen and liver measured at autopsy, indicating splenomegaly and hepatomegaly. The size of these organs was significantly reduced for those treated compared to the control group. The organs were evaluated histopathologically as well and again the treated group had less infiltrated tissue with leukemic cells. Taken all this into consideration, we can say that mulberry anthocyanins

Based on the substitution pattern of anthocyanidins, a recent study reported that growth inhibition of HT29 cells (human colon cancer) was highly affected by delphinidin and malvidin, while pelargonidin exhibited the lowest growth inhibitory potential. Moreover, same study reported that malvidin could inhibit the activity of phosphodiesterase (PDE) and the hydrolysis of cAMP effectively in HT29 cells thereby inhibiting the MAPK signaling pathway [76]. Another research paper [77] investigated anthocyanin-rich extracts from grape (*Vitis vinifera*), bilberry (*Vaccinium myrtillus* L.), and chokeberry (*Aronia melanocarpa* E.) for their potential

analyzed, where effects similar to *in vitro* studies were observed [75].

can improve or eliminate the leukemic mice disorder [86].

Human epidermal growth factor 2 (HER2) is a member of the epidermal growth factor receptor family which is overexpressed in breast cancer, and to study the *in vitro* effect of anthocyanins, the cell lines in breast cancer are usually HER2 positive; unfortunately, there are many other types of breast cancer that occur due to other causes. Regarding potential chemopreventive effects of anthocyanins, recently, it was demonstrated that black rice anthocyanins reduce the adhesion, migration, and invasion of HER2 MDA-MB-453 cells. The morphology of these cells was significantly altered, moving from a mesenchymal to an epithelial state. The western blot analysis shows an increase of the epithelial marker, E-cadherin, and decreased the expression of the mesenchymal markers, fibronectin and vimentin; this shows the effect that BRAC has on epithelial mesenchymal transition (EMT). EMT is a process by which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties which occurs in the initiation of metastasis in cancer progression [4]. An important role in the metastasis of MDA-MB-453 cells is the focal adhesion kinase (FAK)-signaling pathway. FAK promotes the increased expression of transcription factors associated with EMT. The cells used in certain analysis were treated with Y15 (FAK inhibitor) that inhibits the autophosphorylation site of FAK. The study shows that BRAC has a similar effect to Y15, and also BRAC decreases the activation and transduction of FAK signaling [79].
