Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells

Abstract

Saponins are natural compounds found in plants and have a diverse range of applications. However, the therapeutic potential of saponins in regulating cytotoxicity, angiogenesis, and inflammation in mammalian cells is yet to be explored. Here, we investigated the therapeutic effects of saponins from green tea by exploring the cytotoxic effects of saponins by inducing apoptosis in the human cancer cell lines hepatocellular carcinoma (HEPG2) and colorectal adenocarcinoma (HT29). The anti-angiogenesis effect of saponins was also investigated in human umbilical vein endothelial cells (HUVEC). We explored the ability of saponins to attenuate inflammation in a dose-dependent manner in normal human cells. It was found that saponins exhibit cytotoxic effects in cancer cells and not in normal cells at the same concentration. Cytotoxicity was measured by inducing apoptosis by enhancing caspase-3 (cas-3) activation and B-cell lymphoma-2 (Bcl-2)-associated X protein (BAX) gene expression and suppressing the antiapoptotic protein, Bcl-2. The inhibition of HUVEC proliferation was due to the suppression of the phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), vascular endothelial growth factor receptor-2 (VEGFR-2), and nuclear factor kappa B (NF-κB). We also observed the antioxidant potential of green tea-derived saponins against free radicals in reactive oxygen species (ROS)-induced cells. Here we observed that the saponins exhibited free radical scavenging activities and activated nuclear factorerythroid 2-related factor 2 (NRF-2) leading to the upregulation of antioxidant-related genes in human embryonic kidney 293 (HEK293) cells. Furthermore, we demonstrated that the anti-inflammatory effects were due to the suppression of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in HEK293 cells. The significance of the work is we are the first to report on the anti-cancer effects of saponins based on the anti-inflammatory, antioxidant, anti-angiogenesis, and apoptosis induction properties. In conclusion, green tea-derived saponins could be effective therapeutics for the treatment of cancer.

Spermatozoa Quality of Kintamani Dogs in Coconut Water-Egg Yolk Diluent with Addition of Moringa Leaves and Carrot Extract

“…Alkaloids are effective in tackling free radicals by performing scavengers against hydroxyl radicals (Gurudeeban et al 2015). Saponins are effective against free radicals by scavenging the radicals, -diphenyl-βpicrylhydrazyl (DPPH), and 2,20 -azino-bis(3ethylbenzothiazoline-6-sulfonic acid (ABTS) and also H2O2 (Khan et al 2022) Triterpenes, -amyrin, oleanolic acid and ursolic acid combat free radicals by scavenging against nitric oxide (NO•), superoxide (•O2-) and lipid peroxides (LOO•) radicals (Santiago et al 2014). These can neutralize free radicals, thereby preventing oxidative damage to most biomolecules and providing significant protection (Sreelatha and Padma 2010).…”

Advances in the Application of Phytogenic Extracts as Antioxidants and Their Potential Mechanisms in Ruminants

“…As for the anticancer, anti-inflammation, and antioxidation effects of saponins, the findings of some researchers can be summarized as follows. Some compounds, such as saponins from plant extracts, exert cytotoxicity effects against cancer cells, such as HTC-8 (human colon carcinoma), BEL-7402 (human liver carcinoma), and A549 (human lung carcinoma) [ 79 ], which may be attributed to the effects of proapoptosis in the cancer cell lines [ 80 ]. Moreover, saponins have been found to inhibit the expressions of the VE-cadherin and VEGFR-2 complexes, which are key growth factors for vascular remodeling and proliferation via NF-κB downregulation [ 80 ].…”

“…Some compounds, such as saponins from plant extracts, exert cytotoxicity effects against cancer cells, such as HTC-8 (human colon carcinoma), BEL-7402 (human liver carcinoma), and A549 (human lung carcinoma) [ 79 ], which may be attributed to the effects of proapoptosis in the cancer cell lines [ 80 ]. Moreover, saponins have been found to inhibit the expressions of the VE-cadherin and VEGFR-2 complexes, which are key growth factors for vascular remodeling and proliferation via NF-κB downregulation [ 80 ]. Regarding antioxidation effects, saponins exert radical scavenging effects, in turn inhibiting lipid oxidation by breaking chains; therefore, they can function as nutraceuticals and pharmaceuticals [ 80 ].…”

“…Moreover, saponins have been found to inhibit the expressions of the VE-cadherin and VEGFR-2 complexes, which are key growth factors for vascular remodeling and proliferation via NF-κB downregulation [ 80 ]. Regarding antioxidation effects, saponins exert radical scavenging effects, in turn inhibiting lipid oxidation by breaking chains; therefore, they can function as nutraceuticals and pharmaceuticals [ 80 ]. Moreover, saponins can influence hydrogen peroxide-induced ROS production in the liver due to the fact that saponins can activate the expressions of the transcription factors of antioxidant enzymes, such as glutamate cysteine ligase (GCL) and NRF2 [ 81 ], thereby decreasing oxidation stress.…”

Radical scavenging activity of Chlorophytum borivilianum L. root extract and its protective role in cauda epididymal sperm integrity in Mus musculus after gamma irradiation

“…borivilianum usually contains stigmasterol, neotigogenin, hecogenin, alkaloids, phenolic acid, flavonoids, saponins, and palmitic acid ( Visavadiya et al, 2010 ; Giri et al, 2015 ). Among these, stigmasterol ( Pratiwi et al, 2021 ), alkaloids ( Macáková et al, 2019 ), flavonoids ( Jovanovic et al, 1996 ), and saponins ( Khan et al, 2022 ) have been strongly associated with the reduction of oxidative stress and inhibition of ROS generation. Recently, in our previous study, nine compounds have been identified, including 5-methylhex-2-yl pentadecyl ester (23.69%), 9,10-anthracenedione (19.02%), and phthalic acid (18.63%) ( Vyas et al, 2020 ).…”