**6.3. Lung cancer**

Inhibitory effect of anthocyanins on the migration and invasion of lung cancer was also studied. A previous study reported that glycosylated cyanidins isolated from mulberry exerted a dose-dependent inhibitory effect on the migration and invasion of metastatic A549 human lung carcinoma cells. Their results showed that the applied treatments could decrease the expressions of matrix matalloprotinase-2 (MMP-2) and urokinase plasminogen activator (u-PA) in a dose-dependent manner and also enhance the expression of tissue inhibitor of matrix matalloprotinase-2 (TIMP-2) and plasminogen activator inhibitor (PAI). Moreover, Western blot analysis revealed that anthocyanins treatment to A549 cells inhibited the activation of c-Jun (p48) and NF-kB (p65). Further, another study using anthocyanins from fruits of *Vitis coignetiae Pulliat* (AIMs) reported their anticancer effects on lung cancer cells. AIMs inhibited the growth; migration and invasion of A549 cells; and also some proteins involved with cancer effects are inhibited. AIMs suppressed MMP-2 (gelatinase-A) and MMP-9 (gelatinase-B), both involved in the proteolytic digestion of the ECM (extracellular matrix) and cell migration through the basement membranes to reach the circulatory system. Through the immunoblotting results, a large number of proteins have been demonstrated to be suppressed by AIMs. A couple of these proteins are involved in cancer proliferation (COX-2, cyclin D1), migration and invasion (MMP-2, MMP-9), as mentioned before, anti-apoptosis (XIAP), adhesion, and angiogenesis (VEGF). However, they were not able to identify in which signaling pathway is AIMs mainly involved. This study identifies that AIMs might have anticancer effects on human lung cancer [80].

and induces apoptosis. All these events have an effect on the intracellular ROS formation, causing an increase, resulting in the death of tumor cells [82]. In another study, delphinidin and cyanidin, two major compounds in *Hibiscus sabdariffa*, were investigated. They are able to induce cell cycle arrest in human leukemia cell line HL-60. This effect occurs because of their action on signaling pathways whose role is to induce cell cycle arrest. This indicates promis-

Anthocyanins-Smart Molecules for Cancer Prevention http://dx.doi.org/10.5772/intechopen.79613 85

Interests in anthocyanins have increased substantially during the past two decades. In this review, we discussed at what level anthocyanins act when talking about anticancer effects. *In vitro*, we saw that anthocyanins affect: the proliferation of the cancer cells, inhibiting of the ability of cancer cells to divide uncontrollably, the induction of apoptosis, the process of angiogenesis where tumors form new blood vessels, and the cancer cells invasion through healthy tissue. Also, a few of the *in vivo* studies demonstrate that dietary anthocyanins inhibit the growth of different types of tumors, angiogenesis, and show apoptotic effect against the cancer cells. It remains to be determined whether the anticancer activity of anthocyanins is

The authors indicate no potential conflicts of interest. "The authors declare no conflict of interest"; "the founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the

This work was published under the frame of a national grant financed by Romanian National Authority for Scientific Research (UEFISCDI) project number PN-III-P2-2.1-PED-2016-1002, 186PED, 01/09/2017. The work of Dumitriţa Ruginǎ is sustained by the National Fellowship

ing anticarcinogenic effects [83].

due to anthocyanins or their metabolites.

Program L'Oréal-UNESCO-For Women in Science.

ROS reactive oxygen species

ARE anthocyanin-rich extract

PDE phosphodiesterase

**Conflicts of interest**

**Funding statement**

**Abbreviations**

results."

**7. Conclusions**

### **6.4. Skin cancer**

Several studies have demonstrated that flavonoids are one of the candidates for prevention of the adverse effects of UV radiation due to their UV absorbing property, and antioxidant properties. In this context, a published study revealed that grape seed proanthocyanidins (GSP) inhibits cell growth, induces G1-phase arrest, promotes apoptosis in human epidermoid carcinoma A431 cells through alterations in Cdki-Cdk-cyclin cascade, and caspase-3 activation via loss of mitochondrial membrane potential [81]. Many other studies have also proved the antiproliferative and proapoptotic effects of anthocyanins on melanoma or others skin diseases [82–84]. Our latest published revealed that anthocyanins may inhibit melanoma cell proliferation, increase the level of oxidative stress, and diminished mitochondrial membrane potential [84].

#### **6.5. Prostate cancer**

Cyanidin-3-O-β-glucopyranoside (C3G) is well known to be found in a lot of anthocyaninrich fruits, like berries. To study its effect on cancer, two cells lines were used, LnCap and DU145. These cell lines were chosen because DU145 is a tumor cell line androgen-independent and LnCap is androgen-dependent. Androgen-dependent prostate cancer is characterized by the absence of the androgen receptor due to promoter methylation. In this case, the treatment is based on hormone elimination, yet other approaches are needed if the amount of hormones does not affect the development of cancer [79]. C3G causes a decrease in cell viability in both cell lines, and apoptosis is also induced, DU145 being more responsive in this aspect. The positive effect of treatment is demonstrated by the activation of caspase 3 and a significant increase in expression of p21 protein, evidence that cells undergo apoptosis [80]. Another study focuses on proteins that indicate the presence of apoptosis such as p53 and Bax. P53, or "the guardian of the genome" is a suppressor tumor protein that initiates apoptosis in degraded DNA cells, and Bax is a pro-apoptotic protein of the Bcl-2 family [81].
