Study on Lycopene and Cancer

Lycopene is a natural pigment that is widely distributed in nature, mainly found in plants such as tomatoes, plums, watermelons, guavas, carrots, papayas, etc. It is especially abundant in tomatoes. In general, the more mature the tomato, the higher the lycopene content. It has also been found in microorganisms. Lycopene belongs to the isoprenoid compounds and is a type of carotenoid. Its molecular structure contains a highly unsaturated hydrocarbon chain, which gives it strong antioxidant properties. Its chemical formula is C40 H56 and its structural formula is shown in Figure 1.

Lycopene, as a precursor that can synthesize carotene, not only has important nutritional and functional effects on the human body, but also has a wide range of important biological functions, such as anti-cancer, prevention of cardiovascular disease and neurodegenerative diseases, prevention of atherosclerosis, liver protection, enhancement of human immunity, anti-radiation, anti-aging, etc. [1], so research on it is increasing. Lycopene, as a new type of functional natural pigment, has shown important application value and broad prospects in the fields of food, medicine, and health products due to its good biological activity. This article mainly reviews the research on the anticancer effect and biological mechanism of lycopene, with the aim of providing new methods to improve people's health and quality of life.

1 The anticancer effect of lycopene

According to epidemiological data analysis, increasing the intake of lycopene in the diet can significantly reduce the probability of the body developing malignant tumors. In vitro experiments have also shown that lycopene has a significant inhibitory effect on many cancer cells [1].

1.1 The effect of lycopene on prostate cancer

Prostate cancer is the second most common cancer among men worldwide. Epidemiological studies have shown that increasing lycopene intake can help reduce the risk of prostate cancer. Research has shown [2] that lycopene can inhibit the inflammatory response by reducing inflammatory factors such as interleukin-1/6/8 (IL-1/6/8) and tumor necrosis factor-α (TNF-α), thereby inhibiting the proliferation, survival and metastasis of prostate cancer cells, promoting apoptosis of cancer cells, increasing the survival time of mice, and the effect is dose-dependent. Cell adhesion and TNF-α) can inhibit the inflammatory response, thereby inhibiting the proliferation, survival and metastasis of prostate cancer cells, promoting apoptosis of cancer cells, increasing the survival time of mice, and the effect is dose-dependent. Cell adhesion and migration are important features of cancer progression, which can be used as targets to intercept cancer development. Simone E et al. [3] showed that lycopene can significantly reduce the adhesion and migration properties of cancer cells. Angiogenesis is also an important factor in cancer progression. Increasing the intake of lycopene in the diet can inhibit tumor angiogenesis and reduce mortality from prostate cancer [4]. Increasing the intake of lycopene in the daily diet can also reduce the risk of developing prostate cancer [5].

1. 2 The effect of lycopene on breast cancer

Breast cancer (BC) is the most common cancer among women worldwide. Dietary carotenoids, especially lycopene, can reduce the risk of BC. Studies have shown [6] that lycopene can inhibit the G0/G1 phase of the cancer cell cycle, hinder cell growth and proliferation, and induce apoptosis. Its main mechanism is to inhibit the phosphorylation activity of the serine/threonine protein kinase Akt and down-regulate the expression of its downstream molecules mammalian Target of Rapamycin Complexity (mTORC) and cyclin D1, as well as up-regulate the expression of the pro-apoptotic factor Bax. The effect of lycopene is positively correlated with time and dose.

The Akt phosphorylation signal pathway in cancer cells is overactivated. mTORC) and cyclin D1 expression, and upregulates the expression of the proapoptotic factor Bax. The effect of lycopene is positively correlated with time and dose. The overactivation of the Akt phosphorylation signaling pathway and the overexpression of mammalian Target of rapamycin complex (mTORC) in cancer cells can stimulate the occurrence and development of breast tumors. Estrogen receptor (ER)-positive breast cancer is the most common type of breast cancer.

This cancer pathway includes ER-dependent and ER-independent, of which the former involves estrogen binding to ER to induce cell growth and proliferation, while the latter produces toxic metabolites such as free radicals and reactive oxygen species through estrogen metabolism. Both pathways synergistically induce breast cancer [7]. Finding natural antioxidants is important for the prevention and treatment of ER-positive breast cancer. Lycopene and tocopherols have strong synergistic antioxidant properties. They can significantly reduce the MDA and NO levels induced by DMBA (dimethylbenz[a]anthracene) in female rat breast cancer cells, increase the contents of SOD, CAT and GSH-Px, reduce oxidative stress, and pathological sections show improved tumor formation and angiogenesis. The synergistic effect of lycopene and β-carotene can inhibit cell proliferation, can arrest differentiation in different cell cycles and induce apoptosis [8-9].

1. 3 The effect of lycopene on ovarian cancer

Ovarian cancer is one of the most common malignant tumors of the reproductive organs in women, and its mortality rate ranks first among gynecological malignancies. Because the ovaries are located deep in the pelvis, the onset of the disease is relatively hidden. At the time of diagnosis, more than 70% of patients have advanced or metastatic disease. Surgery and radiotherapy have low efficacy and side effects, which seriously threaten women's health. It is of great significance to find natural and effective drugs without side effects. Some data show [10] that increasing the intake of lycopene in the diet can reduce the risk of ovarian cancer in postmenopausal women, mainly due to its antioxidant activity. Nina et al. [11] showed that lycopene can reduce the expression of the ovarian cancer biomarker CA125 and inhibit the metastasis and proliferation of cancer cells, which is related to the downregulation of its related markers and the regulation of related protein expression. Lycopene combined with paclitaxel and carboplatin can significantly reduce the number of ovarian cancer cells that survive. These findings suggest that lycopene can interfere with the mechanism of ovarian cancer development and progression, and has preventive and therapeutic effects on ovarian cancer. Combined with chemotherapy, it can reduce the burden of ovarian cancer development and metastasis in vivo.

1. 4 The effect of lycopene on gastrointestinal cancer

Gastric cancer (GI) has become the second most common cancer in the world and has the highest mortality rate. Its occurrence and development are related to people's diet. Some studies have shown [12] that lycopene can inhibit the growth and proliferation of gastric cancer cells, and the main mechanism is related to the inhibition of extracellular signal-regulated kinase (ERK). The ERK signaling pathway is key to transmitting signals from surface receptors to the cell nucleus, and is involved in a variety of biological responses such as cell proliferation and differentiation, maintenance of cell shape, construction of the cytoskeleton, apoptosis and cell carcinogenesis. This signaling pathway is overactivated in cancer cells. Colon cancer has become the third most common cancer in the world, and there is evidence that increasing lycopene intake in the diet can reduce the incidence of intestinal cancer. Some articles have shown [13] that lycopene and nanogold work together to inhibit the metastasis and invasion of colon cancer cells HT-29 and promote apoptosis.

2   Lycopene's anti-cancer mechanism

2. 1   Lycopene's antioxidant activity

The level of reactive oxygen species (ROS) in cancer cells can increase significantly, which can overactivate multiple cell signaling pathways, such as nuclear factor-κB (NF-κB) and its target genes (cIAP1, cIAP2) and the expression of survival proteins, slowing down the apoptosis process of cancer cells. NF-κB is a transcription factor plays a key role in cell survival, growth, differentiation, metastasis and adhesion. cIAP1/2 belongs to the Inhibitor of apoptosis proteins (IAPs), a highly conserved family of endogenous anti-apoptotic factors. It mainly promotes cell proliferation and survival by inhibiting Caspase activity and participating in the regulation of the nuclear factor NF-κB, thereby inhibiting apoptosis. The NF-κB signaling pathway is hyperactivated, further promoting the occurrence of cancer [14-15]. Targeting NF-κB may be an effective way to develop anti-human cancer treatments. Yoon-seon et al. [15] demonstrated that lycopene has strong antioxidant activity, can reduce intracellular and mitochondrial ROS levels, and NF-κB activity, and can increase Caspase-3 activity and the Bax/Bcl-2 ratio, affecting the survival rate of cancer cells and promoting apoptosis.

2. 2 Effect of lycopene on COX-2

Many studies have shown [16-18] that cyclooxygenase-2 (COX-2) is a key enzyme in fatty acid metabolism. It is highly inactive in normal tissue cells, but is overexpressed in many cancer cells and in response to inflammatory damage. At the same time, excessive COX-2 can induce the production of prostaglandins, which in turn promote carcinogenesis, manifested in the promotion of cancer cell proliferation and angiogenesis, inhibit apoptosis, etc. Vasconcelos et al. [19] showed that lycopene extracted from guava can inhibit the expression of COX-2 to inhibit the growth and proliferation of colon cancer cells and induce apoptosis. This mechanism is mainly that lycopene's strong antioxidant and anti-inflammatory activities reduce inflammatory responses, inhibit the expression of COX-2, and induce apoptosis of tumor cells.

2. 3 Lycopene's effect on cell-to-cell communication

Cell-to-cell communication is mainly mediated by gap junctions communication (GJC), which refers to a special type of membrane communication that allows small molecules and ions to pass through multiple channels directly to the cytoplasm between adjacent cells. GJC has an effect on regulating cell proliferation, differentiation and apoptosis. Studies have shown [20] that the absence of cell-to-cell junction communication is a sign of carcinogenesis. Some articles have shown [21] that lycopene can upregulate the level of CJC. The main mechanism is that both the oxidative metabolites and enzymatic cleavage metabolites of lycopene affect GJC, possibly providing two ways to increase GJC.

2. 4 The effect of lycopene on cancer cell proliferation and apoptosis

The ROS level in cancer cells is significantly higher than that in normal cells. Excessive ROS can activate the epidermal growth factor receptor (EGFR), which further activates the Ras/mitogen-activated protein kinases/extracellular regulating kinase (Ras/MAPK/ERK) signaling pathway. Ras / MAPK / ERK), which activates the signal pathway to promote cell overgrowth, proliferation, and reduce the effect of apoptosis. Hwana et al. [21] showed that lycopene can inhibit the expression of the EGFR / Ras / MAPK / ERK signal pathway and reduce the survival rate of gastric cancer cells. In addition, the strong antioxidant activity of lycopene can reduce the intracellular ROS content and promote apoptosis.

2. 5   Lycopene's effect on the Wnt / β-catenin pathway

Cancer complications can be divided into direct and indirect complications, with the latter including invasion and immunosuppression. Carcinogenesis affects a variety of molecular mechanisms and pathways in the body, including changes in homeostasis. Among these, the Wnt / β-catenin transduction pathway is an important mediator in maintaining homeostasis and is essential for maintaining homeostasis and tissue homeostasis. The phosphorylation of β-catenin in cancer cells is increased, inhibiting the apoptotic pathway. Raghada Khalid et al. [22] showed that lycopene has a significant effect on inhibiting the phosphorylation of β-catenin and upregulating the expression of the Wnt/β-catenin signaling pathway, and further demonstrated that lycopene regulates the apoptotic pathway and promotes the upregulation of Wnt/β-catenin expression.

3 Lycopene and its product applications

According to the official website of the China Food and Drug Administration (CFDA), there are 31 health products containing lycopene that have been approved by the State Food and Drug Administration. These products are mainly used for anti-oxidation, anti-aging, immunity enhancement, and blood lipid regulation. Two of these products are tablets, one is an oil, and the rest are capsules. In cosmetics, typical products such as lycopene moisturizing lotion have whitening and anti-aging effects. In the food processing industry, lycopene powder is used as a food additive for flavoring, coloring, preservation, and antiseptic purposes. Lycopene is a carotenoid compound with great potential. The body cannot synthesize it on its own and it must be supplemented through the diet. After extensive research on the physiological functions of lycopene, companies such as Henkel in the United States and Makhtshim in Japan have produced drugs with lycopene as the main active ingredient. Its main effects include lowering blood pressure, treating high blood cholesterol and high blood lipids, and inhibiting cancer cells. At present, there are few reports of lycopene being used as a food or pharmaceutical ingredient in China.

4 Outlook

Cancer is the leading cause of death in humans. Traditional treatments include chemotherapy and radiotherapy. However, this method can cause cancer cells to become resistant and has significant side effects. Therefore, it is particularly important to find more effective drugs with no side effects. Numerous in vitro and in vivo experiments have demonstrated that lycopene is a natural anti-cancer substance with a dose-dependent anti-cancer effect. Although the anti-cancer mechanism is not very clear, it can inhibit the development of cancer cells by reducing the production of oxidative products, lowering the content of inflammatory factors, and regulating signal pathways. The use of lycopene in cancer prevention not only improves the health of cancer patients, but also improves their quality of life and reduces costs. Further research is needed to investigate the anti-cancer function of lycopene, to further develop its application in health products and pharmaceuticals, and to play an important role in the development and utilization of lycopene-rich resources.

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