In Vivo and in vitro antitumor activity of tomatine in hepatocellular carcinoma

Abstract

Background: There is abundant ethnopharmacological evidence the uses of regarding Solanum species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species.Purpose: To evaluate the anticancer effect of the Solanum glycoalkaloid tomatine in hepatocellular carcinoma (HCC) in vitro (HepG2 cells) and in vivo models.Methods: The resazurin reduction assay was performed to detect the effect of tomatine on cell viability in human HepG2 cell lines. Programmed cell death was investigated by means of cellular apoptosis assays using Annexin V. The expression of cancer related proteins was detected by Western blotting (WB). Reactive oxygen species (ROS) and calcium were determined by 2,7-dichlorodihydrofluorescein diacetate and Fluo-4, respectively. Intrahepatic HepG2 xenograft mouse model was used to elucidate the effect of tomatine on tumor growth in vivo.Results and Discussion: Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death, consistently with caspase-3, -7, Bcl-2 family, and P53 proteins activation. Furthermore, tomatine increased intracellular ROS and cytosolic Ca+2 levels. Moreover, the NSG mouse xenograft model showed that treating mice with tomatine inhibited HepG2 tumor growth.Conclusion: Tomatine inhibits in vitro and in vivo HCC tumorigenesis in part via modulation of p53, Ca+2, and ROS signalling. Thus, the results suggest the potential cancer therapeutic use of tomatine in HCC patients.

Mechanisms of Arachidonic Acid In Vitro Tumoricidal Impact

“…Caspase 3 is absent in MCF-7, but capase 7 is readily activated [ 24 ]. In accordance with our results, caspase 3 was recently shown to be weakly expressed in intact hepatocellular carcinoma HepG2 cells [ 67 ], supporting earlier findings documenting the lower expression of caspase 1 and caspase 3 in hepatocellular carcinoma tissue compared to nontumor cells [ 68 , 69 ]. Conversely, caspase 3 was found to be overexpressed in HepG2 and absent in colon carcinoma cell lines [ 70 ].…”

“…Caspase 3/7 activity in 5 μg proteins of intact and ARA-treated cell homogenate extracts was evaluated using the Caspase-Glo 3/7 Assay of Promega, following the manufacturer’s instructions, whereby released luminescence minus background values is proportional to the amount of caspase activity present [ 19 , 67 , 89 , 90 ].…”

Agri-Food Waste Recycling for Healthy Remedies: Biomedical Potential of Nutraceuticals from Unripe Tomatoes (Solanum lycopersicum L.)

“…The mechanism of its anti-tumoral activity seems to include the disruption of tumor cell membranes, cell cycle arrest, and the inhibition of DNA replication [115]. In human hepatocarcinoma cells (HepG2), α-tomatine (30 µM) triggers apoptosis via the stimulation of caspases 3 and 7, two potent pro-apoptotic factors, as well as the inhibition of the expression of the anti-apoptotic protein Bcl-2 [93,116].…”

Perspective Chapter: Natural Adjuvants for Mucosal Vaccines – The Promise of Tomatine as an Inherent Adjuvant in Tomatoes

“…In the context of cancer, tomatine has shown promising results in inhibiting cell invasion and melanoma-dependent angiogenesis by reducing the release of vascular endothelial growth factor (VEGF) and interfering with tumor-stimulating effects on capillary tube formation, thus exerting suppressive effects on melanoma progression [29]. Moreover, tomatine has exhibited potent anti-inflammatory and anticancer effects both in vitro and in vivo, particularly against androgen-independent prostate cancer [15,42], hepatocellular carcinoma [43], non-small cell lung cancer [44], breast [45], and ovarian cancer [46].…”