Sugiol, a natural compound with anticancer properties, has shown promise in various
cancer types, but its potential in preventing
gastric cancer remains uncertain. In this study, we aimed to examine the inhibitory effect of
sugiol on human
gastric cancer cell proliferation. Our findings demonstrate that
sugiol effectively suppresses the proliferation of SNU-5 human
gastric cancer cells, leading to apoptotic cell death. We assessed the chemo-preventive potential of
sugiol via an MTT assay and confirmed the induction of oxidative stress using the
H2DCFDA fluorescent dye. Treatment with
sugiol at concentrations higher than 25 µM for 24 h resulted in an increase in intracellular levels of
reactive oxygen species (ROS). This elevation of ROS levels inhibited cell-cycle progression and induced cell-cycle arrest at the G1 phase. Furthermore, our study revealed that
sugiol reduces the viability and proliferation of SNU-5 cells in a dose-dependent manner. Importantly, ADME and toxicity analyses revealed that
sugiol was effective and nontoxic at low doses. In parallel, we utilized the Swiss target prediction tool to identify potential targets for
sugiol.
Enzymes and
nuclear receptors were identified as major targets. To gain insights into the molecular interactions, we performed structure-based molecular docking studies, focusing on the interaction between
sugiol and STAT3. The docking results revealed strong binding interactions within the active site pocket of STAT3, with a binding affinity of -12.169 kcal/mole.
Sugiol's -
OH group, carbonyl group, and phenyl ring demonstrated hydrogen-bonding interactions with specific residues of the target
protein, along with Vander Waals and hydrophobic interactions. These data suggest that
sugiol has the potential to inhibit the phosphorylation of STAT3, which is known to play a crucial role in promoting the growth and survival of
cancer cells. Targeting the dysregulated STAT3 signaling pathway holds promise as a therapeutic strategy for various human
tumors. In combination with interventions that regulate cell cycle progression and mitigate the DNA damage response, the efficacy of these therapeutic approaches can be further enhanced. The findings from our study highlight the antiproliferative and apoptotic potential of
sugiol against human
gastric cancer cells (SNU-5). Moreover, the result underpins that
sugiol's interactions with STAT3 may contribute to its inhibitory effects on
cancer cell growth and proliferation. Further research is warranted to explore the full potential of
sugiol as a therapeutic agent and its potential application in treating
gastric cancer and other
malignancies characterized by dysregulated STAT3 activity.