Evaluation of the Effects of Genistein In Vitro as a Chemopreventive Agent for Colorectal Cancer—Strategy to Improve Its Efficiency When Administered Orally

Abstract

Colorectal Cancer (CRC) ranks third in terms of incidence and second in terms of mortality and prevalence worldwide. In relation to chemotherapy treatment, the most used drug is 5-fluorouracil (5-FU); however, the use of this drug generates various toxic effects at the systemic level. For this reason, new therapeutic strategies are currently being sought that can be used as neoadjuvant or adjuvant treatments. Recent research has shown that natural compounds, such as genistein, have chemotherapeutic and anticancer effects, but the mechanisms of action of genistein and its molecular targets in human colon cells have not been fully elucidated. The results reported in relation to non-malignant cell lines are also unclear, which does not allow evidence of the selectivity that this compound may have. Therefore, in this work, genistein was evaluated in vitro in both cancer cell lines SW480 and SW620 and in the non-malignant cell line HaCaT. The results obtained show that genistein has selectivity for the SW480 and SW620 cell lines. In addition, it inhibits cell viability and has an antiproliferative effect in a dose-dependent manner. Increased production of reactive oxygen species (ROS) was also found, suggesting an association with the cell death process through various mechanisms. Finally, the encapsulation strategy that was proposed made it possible to demonstrate that bacterial nanocellulose (BNC) is capable of protecting genistein from the acidic conditions of gastric fluid and also allows the release of the compound in the colonic fluid. This would allow genistein to act locally in the mucosa of the colon where the first stages of CRC occur.

Genistein–Aspirin Combination Exerts Cytotoxic and Anti-Migratory Effects in Human Colorectal Cancer Cells

“…Our data showed a concentration-dependent (10-75 µM) reduction in HCT-116 cells' viability (Figure 1), significant alterations of cellular morphology, a slight inhibitory effect on HCT-116 cells' migratory capacity, and the reorganization of actin cytoskeleton and nuclear changes. These results are supported by other studies that demonstrated the anticancer effects of genistein in different colon cancer cells exerting multiple mechanisms of action, as follows: (i) in HT-29 and SW620 cells, genistein decreased cells' viability and increased oxidative stress and inflammation [30]; (ii) in HT29 cells, genistein suppressed cells' migration and invasion by inducing demethylation and recovering the activity of WNT inhibitory factor 1 (WIF1), a tumor suppressor [15]; (iii) in SW480 and SW620 cells, genistein triggered a dose-dependent antiproliferative effect and inhibited cells' viability via apoptosis [14]; (iv) in HCT-116 cells, genistein induced apoptosis and suppression of cells' proliferation by interfering with miR-95, Akt and SGK1 signaling transduction pathways [12], (v) in SW480, genistein treatment caused cell cycle arrest, inhibition of cells' proliferation, and histone acetylation [31]; and (vi) in HCT-116 and LoVo cells, genistein induced the mitochondrial pathway of apoptosis by suppressing phosphorylation of Akt [32], etc. The anticancer potential of genistein was also proved in other preclinical models of breast cancer, gastric cancer, hepatocellular carcinoma, and salivary adenoid cystic carcinoma [27].…”

“…The anticancer potential of genistein was also proved in other preclinical models of breast cancer, gastric cancer, hepatocellular carcinoma, and salivary adenoid cystic carcinoma [27]. The main advantage of genistein is the low/non-toxic profile [14,33].…”

“…This natural compound possesses various biological effects; it is antioxidant, anti-inflammatory, antiangiogenic, protective against osteoporosis, decreases the risk of cardiovascular pathology, palliates postmenopausal symptoms, and promotes anticancer activity [10]. With regard to GEN's impact in CRC, a number of preclinical studies described several mechanisms of action, such as (i) a decrease in cellular proliferation, induction of apoptosis, and suppression of the epidermal growth factor receptor (EGFR), as well as of estrogen receptor 1 (ESR1) expressions in colorectal cancer cells (HCT-116) [11]; (ii) inhibition of HCT-116 cells proliferation, inhibition of apoptosis, down-regulation of Akt, SGK1 and miR-95 mRNA expressions, and suppression of tumor growth in vivo [12]; (iii) inhibition of colon cancer cells' (HT-29) migration by reversing epithelial-to-mesenchymal transition via suppression of the Notch1/NF-κB/slug/E-cadherin pathway [13]; (iv) induction of apoptosis in colorectal cancer cell lines SW480 and SW620 by stimulating the oxidative reactive species (ROS) production [14]; and (v) suppression of colon cancer cells' (HT-29) invasion and migration via demethylation and modulation of Wnt signaling pathway [15].…”

Design and development of artificial intelligence‐based application programming interface for early detection and diagnosis of colorectal cancer from wireless capsule endoscopy images

“…Colorectal cancer (CRC) ranks third in terms of global cancer incidence as reported by WHO. Additionally, it is ranked as the second most prevalent cause of cancer‐related mortality on a global scale 1 . It is anticipated by the International Agency for Research on Cancer (IARC) that the newly diagnosed cases of CRC will exceed the figure of 3 million each year by 2040 2 …”

“…Additionally, it is ranked as the second most prevalent cause of cancerrelated mortality on a global scale. 1 It is anticipated by the International Agency for Research on Cancer (IARC) that the newly diagnosed cases of CRC will exceed the figure of 3 million each year by 2040. 2 A colorectal polyp is an abnormal non-cancerous tissue growth that extends towards the lumen of the colon and rectum from the mucosal lining.…”