**4. Final considerations and conclusions**

and capsaicinoids, among others [40, 58, 59, 61]. Controversy remains regarding the beneficial and unfavorable health effects of chili consumption. Recently, Chopan and Littenberg [18] determined that there is no direct relation between high consumption of red chilis and mortality in various populations of North America and Europe. In these cases, adult consumers of red chilis showed a 13% lower risk of death than non-consumers. Lv et al. [104] also observed no direct relation between consumption of fresh or dried chilis and causes of mortality from cancer, diabetes, respiratory or cardiac diseases. Other reports argued that the bioactive or phytochemical compounds of *Capsicum* have anti-inflammatory, antidiabetic, antimicrobial,

Cancer is one of the primary causes of morbidity and mortality worldwide. Oxidative stress is implied in the etiology of this disease and results from imbalances in the production of reactive oxygen species (ROS) and the antioxidant defense system of cells. ROS deregulate redox homeostasis and promote formation of tumors by aberrant induction of signaling pathways that cause cancerous tumors [105]. ROS modulate different pathways of cell signaling, which are mediated by the transcription factors NF-κB and STAT3, hypoxia-inducible factor, growth factors, kinases and other proteins and enzymes involved in the development of cancer [106]. In this carcinogenic process, it is argued that capsaicinoids (capsaicin and hydrocapsaicin) help eliminate reactive oxygen species and consequently demonstrate anticarcinogenic, antimutagenic and preventative properties [107, 108]. These properties help prevent the proliferation of cells, migration and induction of apoptosis [109]. In in vivo and in vitro trials, capsaicin inhibited the growth and proliferation of prostate cancer [110]. In addition, capsaicin stimulates the cascade of MAP protein kinase signaling, extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK), which have antiproliferative effects [111]. Capsaicin also induces apoptosis of both androgen receptors AR-positive (LNCaP) and -negative (PC-3, Du-145) prostate cancer cell lines by increasing p53, p21 and Bax [112]. Other studies determined that capsaicin can regulate the increase in IL-6 by secretion of TNF-α and

Capsaicin can prevent the growth of colorectal cancer cells by suppression of pathways dependent on β-catenin/TCF by proteosomal degradation of β-catenin and breakdown of β-catenin/TCF-4 interactions [113]. In addition, capsaicin induces apoptosis in gastric cancer cells and can serve as an antitumor agent in gastric cancer [114]. In other studies, capsaicin generates ROS through mitochondria and the depletion of intracellular antioxidants and gen-

Dihydrocapsaicin showed strong antibacterial activity against *Helicobacter pylori*, the bacteria associated with gastric cancer [116]. In biological trials in vivo, oral administration of quercetin generated decreases in infection from *H. pylori* in gastric mucosa and reduced the inflam-

Flavonoids are molecules that not only act as conventional antioxidant hydrogen donors but also exert a modulatory action on the signaling of protein and lipid kinases of cells [117]. The apigenin flavonoid is an inhibitor of protein kinases and has an antiproliferative effect on breast cancer cells [118]. The aglycone of quercetin has a protective effect on DNA, which is induced by mitomycin C and antiproliferative activities in human lymphocytes [119]. This

anticholesterolemic, anticoagulant and antioxidant properties [63].

424 Flavonoids - From Biosynthesis to Human Health

the signaling responsible for activation of Akt, ERK and PKC-α [110].

erates mitochondrial damage and apoptosis in pancreatic cancer cells [115].

matory response and lipid peroxidation [62].

Chili peppers are used worldwide as food and spices. In Mexico, chilis have great economic, social and culinary importance with variations in consumption per capita from 8 to 17 kg, and approximately 2.8 × 106 tons are produced and consumed annually. Mexico is the center of origin, domestication and diversification of *C. annuum*, which has engendered more than 150 cultivated and wild *landraces* of wide distribution. Nearly every region in Mexico cultivates or consumes chilis. Indigenous groups and traditional producers are the primary actors responsible for in situ preservation of the diversity of chili landraces, particularly in the central and south-southeastern regions. The wild forms of *C. annuum* var. *glabriusculum* and *C. annuum* var. *annuum* are distributed throughout the country.

Daily consumption ranges from two to four times a week, and it is estimated that between 70 and 80% of the total Mexican rural population regularly consume spicy chilis. This high frequency of consumption has generated an adaptation to consumption of spicy and extremely spicy chilis, and among consumers, the TAS2R38 type 2 gene has been identified as being associated with tongue and palate receptors, which confer upon the chili consumer a higher capacity to not perceive or barely perceive the "burning" sensation of chilis. Into the diversity of landraces and improved varieties, there are non-pungent landraces, for example, Morrón, Dulce, Ancho and Chilaca and types of Morrón varieties such as California, Victoria and others.

Chili fruit contains up to 23 flavonoid compounds and 20 capsaicinoids, differing between landraces because of the effect of crop management, the state of maturation of the fruits and postharvest management and ecological-environmental influences. Capsaicinoids (capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, homocapsaicin, etc.) exert multiple physiological effects on human health, including their potential value in pain relief, cancer prevention and decreased bone loss and as antioxidant activity. Experimentally, anticarcinogenic, antimutagenic and cancer preventative properties have been determined for capsaicin in addition to anti-lipid effects. However, these properties require direct evaluation with regard to human health. The flavonoids quercetin and apigenin, present in chili fruits, have antiproliferative effects on breast cancer cells and exert a protective effect on neuronal cells against the neurotoxicity induced by oxidative stress in Alzheimer's.
