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.