Irfan A. Rather

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.

Candida albicans and Staphylococcus aureus, representing two different kingdoms, are the most frequently isolated pathogens from invasive infections. Their pathogenic attributes, combined with drug resistance, make them a major threat and a challenge to successful treatments, mainly when involved in polymicrobial biofilm-associated infections. In the present study, we investigated the antimicrobial potential of Lactobacillus metabolite extracts (LMEs) purified from cell-free supernatant of four Lactobacillus strains (KAU007, KAU0010, KAU0021, and Pro-65). Furthermore, LME obtained from the strain KAU0021 (LMEKAU0021), being the most effective, was analyzed for its anti-biofilm property against mono- and polymicrobial biofilms formed by C. albicans and S. aureus. The impact of LMEKAU0021 on membrane integrity in single and mixed culture conditions was also evaluated using propidium iodide. The MIC values recorded for LMEKAU0021 was 406 µg/mL, 203 µg/mL, and 406 µg/mL against planktonic cells of C. albicans SC5314, S. aureus and polymicrobial culture, respectively. The LMEKAU0021 at sub-MIC values potentially abrogates both biofilm formation as well as 24 h mature mono- and polymicrobial biofilms. These results were further validated using different microscopy and viability assays. For insight mechanism, LMEKAU0021 displayed a strong impact on cell membrane integrity of both pathogens in single and mixed conditions. A hemolytic assay using horse blood cells at different concentrations of LMEKAU0021 confirmed the safety of this extract. The results from this study correlate the antimicrobial and anti-biofilm properties of lactobacilli against bacterial and fungal pathogens in different conditions. Further in vitro and in vivo studies determining these effects will support the aim of discovering an alternative strategy for combating serious polymicrobial infections caused by C. albicans and S. aureus.