**2.1 Cancer cervical and human papilloma virus (HPV)**

 Current information noticed that almost 100 serotypes of HPV exist. But, 2 of these, 16 and 18 serotypes, are related to the development of cervical cancer in Latin women [14, 17]. During cervical carcinogenesis, a viral protein E6 sequesters to p53 protein. Also, another viral protein called E7 participates in the same process, sequestering Rb protein. In consequence, the arrest of both proteins p53 and Rb induces deregulation in the cell cycle. However, possibly the HPV is not an exclusive aetiology agent that produces this disease. Further information noticed that sex steroid hormone participates in the early stages of cervical carcinogenesis [14]. Previous report evidenced the possible relationship between E7 viral and E2 (17β, also spelled oestradiol), but this is poorly understood [14]. Perhaps, our knowledge about the risk factors that derive from the developed cancer will be increasing but also is necessary to improve our awareness of the prevention and treatment of disease.

*Pharmacology Evaluation of Bioactive Compounds that Regulate Cervical Cancer Cells DOI: http://dx.doi.org/10.5772/intechopen.82258* 

### **2.2 Current therapies against cervical cancer**

 In this context, in Mexico 15% of women are detected with precancerous lesions of cervical cancer, and they could be potentially prevented. Currently, chemotherapy, radiotherapy, hormonal therapy, biological therapy and surgery are the treatments majority employed in the early stages of CC [10, 20, 21]. But, the treatments above mentioned often are associated with certain disadvantages, such as toxicity of chemical agent or drug resistance [22]. For example, *cisplatin* in combination with *bevacizumab* can increase the expectations of survival, but they are scarce to the population. In another case, *paclitaxel* is a chemotherapeutic agent used against ovarian carcinoma, but there is evidence of the resistance for this agent [11]. Also, the use of chemotherapy represents other drawbacks, the undesirable effects, the high cost of treatment and recurrence among patients who had improved [10, 20]. All of these adverse effects are due to the lack of a specific target cancer cell, because chemotherapeutics do not have a cancer-specific receptor, protein or DNA [20]. Another limit, in Mexico, there is one radiotherapy machine available for 2 million Mexican. But, reducing the doses of the chemical agent or employing natural compounds can overcome this significant barrier that exists to eliminate CC [11]. Natural or bioactive compounds are used against multiple illnesses including rheumatic, anthelmintic, diuretic, hypoglycaemia and cancer [23].

#### **2.3 Relationship between ROS and cervical cancer**

 The diseases above mentioned, including CC, could produce free radicals that induce damage to the cells, tissues and organs [12]. However, the proper function of cells depends on the mitochondria's ability to regulate metabolic processes and produce molecules, including free radicals as reactive oxygen species (ROS) [11, 24, 25]. ROS controls both physiological and pathological process related to cell proliferation, invasion cell, and tumour hypoxia and drug resistance [11, 12, 26, 27]. Also, in the cell, a defence system against ROS includes several enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase [28]. However, when the cellular antioxidant systems are damaged, antioxidants are insufficient to neutralise ROS, and then oxidative stress occurs [27, 29]. Moreover, in a pathological process, ROS are responsible for damaging proteins, lipids and nucleic acids [29, 30]. Nonetheless, bioactive compounds are strongly linked to the radical scavenging capacity and protect the cell against oxidative DNA damage [12, 25, 31].

#### **2.4 Alternative therapy among cervical cancer**

The plants, fruits and vegetable contain large amounts of bioactive compounds that act as antioxidant, and they can be used with therapeutic purpose [27, 32, 33]. Among antioxidants, different subclasses are described, (a) flavonoids, (b) phenolic acids and polyphenols, (c) stilbenoids, (d) catechins and (e) tannins, and they are abundant and available in natural products previously mentioned [20, 31, 34]. Other compounds related with their oxidant capacity and ROS productions are listed in **Table 1**. The antioxidants that are most well-known, curcumin, resveratrol and gallic acid, have activity against cancer cell line in vitro [15, 24, 28, 35]. For example, galangin is a flavonoid with various biological effects in different cancer cells [25]. Also, the green tea has cancer-preventive effects due to containing catechins known as EGCG (−)-epicatechin-3-gallate, (−)-epigallocatechin and (−)-epicatechin. Also, CTS extract possesses chlorogenic acid, (+)-catechin, caffeic acid, phloretic acid, veratric acid, hesperidin, quercetin and naringenin. Additionally, fucoidan is a major bioactive


#### **Table 1.**

*List of phenolic compounds. Antioxidant properties can be risen with phenolic compounds described here. However, possible signalling pathways, apoptotic or inflammation, can be affected by this kind of compounds.* 

 compound in *Sargassum polycystum* and demonstrated anti-proliferation, antitumor and anticancer properties [13]. Moreover, pterostilbene can be found in berries and grapes and showed therapeutic effects in a variety of cancer types [36]. Other biocompounds such as triptolide, celastrol and tripchlorolide were isolated from *Tripterygium wilfordii*; these compounds are immunosuppressive and anticancer [37]. Gallic acid is a natural phenolic compound with the potential to act against different cancers or viruses [38]. Further information, extracts from *Annona muricata* leaves were shown to have the capacity to induce apoptosis in HeLa cells, suggesting that the extracts have the potential to be used as a treatment against virus-induced cancer cells [39]. Also, this compound can be used in combination with a chemotherapeutic agent to increase the efficiency of chemotherapy [11].

Also, the genus *Annona* has been shown to have promising compounds, called Annonaceous acetogenins (AGEs), that can be utilised in the treatment of cancer because they induce cell cytotoxicity by inhibiting the mitochondrial complex I, and their capacity of acetogenins to inhibit NADH oxidase was also shown to be important for their antitumour function [40, 41]. However, the biological activities of the compounds obtained from *Annona* species are diverse. For example, the crude extract of *A. crassiflora* significantly alters cell viability of cervical cancer cell lines as well as proliferation and migration and induces cell death [42]. Many studies have described, or continuous screening the anticancer bioactive compounds, and explained the potential of plants against illness [25]. Though,

the success of the prevention or treatment depends on the quality and quantity of bioactive compounds. But, the biological effects and mechanisms of action of flavonoids, phenolic acids, stilbenoids and tannins have been studied lightly.
