**5.1. Colon cancer**

Colon cancer is one of the most prevalent diseases across the world. In the United States, colon cancer is the second most prevalent cause of death from cancer in men and women after lung cancer, with approximately 50,310 causes of death [56]. In Europe, colorectal cancer is the second most common cancer, with 50,000 new cases diagnosed in 2012 [57]. The development of colon cancer is associated with high alcohol consumption, high-fat diet poor in fiber, red meat, obesity, smoking, lack of physical exercise, diabetes, inflammatory bowel disease, and some genetic and epigenetic alterations as: microsatellite instability, chromosomal instability, mutation of p53 gene is one of the familiar genetic changes in the development of colon cancer, and several others [58]. A very recent study published in 2017, used a mouse model, which treated them comparatively with azoxymethan (AOM)/dextran sodium sulfate (DSS) and anthocyanin-rich extract from bilberries for colon cancer development [59]. The anthocyanin extract administered to mice resulted in less inflammation of the colon and a reduced number of tumors than the control group. The formation and the growth of colorectal cancer in AOM/ DSS-treated Balb/c mice were prevented by anthocyanins. Another *in vivo* study investigated the chemopreventive activity of commercially available anthocyanin-rich extracts of bilberry, chokeberry, and grape prepared for the food industry [60] Colon cancer male rats treated with a colon carcinogen, azoxymethane, had multiple biomarkers investigated such as: the number and multiplicity of colonic aberrant crypt foci, colonic cell proliferation, urinary levels of oxidative DNA damage, and expression of cyclooxygenase (COX) genes. Compared to the control group, rats fed with different extracts showed several changes. In rats fed with bilberry, chokeberry, and grape extracts, the number of large aberrant crypt foci was reduced. The bilberry and chokeberry diet decreased the colonic cellular proliferation, and the grape and bilberry diets had lower COX-2 mRNA expression of gene. These results clearly support the chemopreventive activity of tested extracts.

many other types of cancer (e.g., breast and prostate). Also, there are no standard practices for the prevention of lung cancer recurrence and metastasis, so there is a great need for some unconventional, user-friendly approaches to improve the treatment and prevent or delay the recurrent lung disease. A recent study published in 2016, investigated the tumor inhibitory activity of diet supplemented with blackberry, alone and in combination with black raspberry, against lung tumor xenograft using nude mice [65]. Their findings indicated that the mixture of blackberry and black raspberry resulted in higher inhibition of tumor growth vs. blackberry alone. Also, the combination between delphinidin (bioactive in blackberries) and punicalagin (bioactive in black raspberry, which gets converted to ellagic acid *in vivo*) determined a higher tumor growth inhibition than delphinidin alone. In another study, two bioactive compounds, peonidin 3-glucoside and cyanidin 3-glucoside, were isolated and identified the from *Oryza sativa* L. Moreover, those compounds were used to treat various cancer cells. They have demonstrated the inhibition on the growth of Lewis lung carcinoma

Anthocyanins-Smart Molecules for Cancer Prevention http://dx.doi.org/10.5772/intechopen.79613 81

Malignant melanoma of skin accounted for 232,000 new cases, and the regions affected are largely those with white populations [57]. Melanoma skin cancer originates in melanocytes, specialized pigment-producing cells found in both the basal layer of the epidermis. Solar UVB radiation has been implicated as the main cause for skin cancer [67]. Early diagnosis is the key for curing this potentially deadly disease. Also prevention is playing a crucial role in spotting melanomas at earlier and more curable stages [68]. Biochemotherapy, the coadministration of traditional chemotherapeutic drugs and biological agents, show a higher response rate for patients than classical treatments that are based only on chemotherapy alone [69–72]. Most anticancer treatments are derived from natural resources such as marine, microbial, and botanical sources [72]. Natural supplements, a rich diet in antioxidants used as a complementary medication, become a common field of research in order to develop new products originating from natural sources with antioxidant and chemopreventive properties. The ability of anthocyanins to influence parameters of skin tumor development on mice was demonstrated in various studies. SKH-1 hairless mouse was used in order to investigate the photo-chemopreventive effect of delphinidin on UVBinduced biomarkers of skin cancer development [17]. After the treatment, the results suggest that delphinidin inhibited UVB-mediated oxidative stress and reduced DNA damage, thereby protecting the cells from UVB-induced apoptosis. The antitumor activity of the anthocyanins extract from *Fructus Sorbi aucupariae* on B-16 melanoma in C57BI/6 mice was also demonstrated [73]. The study revealed an increase in the counts of stromal progenitor cells in the tumor node and their accelerated maturation. The potentiation of the antimetastatic activity of the cytostatic was demonstrated as well. The inhibitory effects of mulberry anthocyanins on the metastasis of B16-F1 cells under noncytotoxic concentrations were investigated. The findings of the study have demonstrated that mulberry anthocyanins have strong anticancer effects by inhibiting the metastasis ability of B16-F1 cells. Further investigations revealed that the antimetastatic effect of these compounds was also evident

cells *in vivo* [66].

**5.4. Skin cancer**

in a C57BL/6 mice model.

#### **5.2. Breast cancer**

Breast cancer is the second most common cause of cancer-associated mortalities in women. The American Cancer Society estimated that 60,290 new cases of breast carcinoma *in situ* were expected to be diagnosed among women in the United States during 2015 [61]. Understanding the biology of the human epidermal growth factor receptor 2 (HER2) helps with the classification, prognosis, and treatment of breast cancer because of the overexpression of HER2 identified in 15–20% cases. HER2 is involved in proliferation, angiogenesis, invasion, and metastasis [62]. A group of scientists have used injection of cyaniding-3-glucoside and peonidin-3-glucoside to evaluate the effect on the tumors of the rats used in the experiments [63]. Compared with the control group, the tumors treated with cyanidin-3-glucoside and peonidin-3-glucoside expressed lower levels of HER2 as well as Ki67, a proliferation marker, demonstrated with histopathological studies. Also, the treated tumors expressed higher levels of caspase 3, showing the apoptotic effect of the treatment. A recent published study [64] evaluated the cytotoxicity of an anthocyanin-rich extract from black rice (AEBR) on breast cancer cells *in vitro* and *in vivo*. This study demonstrated that black rice extract has promising roles against breast cancer. The oral administration of anthocyanin-rich extract from black rice (100 mg/kg/day) on nude mice bearing MDAMB-453 cell xenografts, significantly suppressed tumor growth and angiogenesis, as well as antagonized VEGF activity.

#### **5.3. Lung cancer**

Lung cancer emerged as the most common cancer worldwide, with 1.8 million new cases in 2012 [57]. The treatment and prevention for lung cancer remains scarce, comparing too many other types of cancer (e.g., breast and prostate). Also, there are no standard practices for the prevention of lung cancer recurrence and metastasis, so there is a great need for some unconventional, user-friendly approaches to improve the treatment and prevent or delay the recurrent lung disease. A recent study published in 2016, investigated the tumor inhibitory activity of diet supplemented with blackberry, alone and in combination with black raspberry, against lung tumor xenograft using nude mice [65]. Their findings indicated that the mixture of blackberry and black raspberry resulted in higher inhibition of tumor growth vs. blackberry alone. Also, the combination between delphinidin (bioactive in blackberries) and punicalagin (bioactive in black raspberry, which gets converted to ellagic acid *in vivo*) determined a higher tumor growth inhibition than delphinidin alone. In another study, two bioactive compounds, peonidin 3-glucoside and cyanidin 3-glucoside, were isolated and identified the from *Oryza sativa* L. Moreover, those compounds were used to treat various cancer cells. They have demonstrated the inhibition on the growth of Lewis lung carcinoma cells *in vivo* [66].
