Chemotherapeutic potential of lupeol against cancer in pre-clinical model: A systematic review and meta-analysis

Background: Extensive research on Lupeol's potential in cancer prevention highlights its ability to target various cancer-related factors. It regulates proliferative markers, modulates signaling pathways, including PI3K/AKT/mTOR, and influences inflammatory and apoptotic mechanisms. Additionally, Lupeol demonstrates selectivity in killing cancer cells while sparing normal cells, thus minimizing the risk of toxic effects on healthy tissues. Hypothesis: Therefore, we aimed to explore Lupeol's potential roles as a chemotherapeutic agent and as a sensitizer to chemotherapy by reviewing various animal-based studies published on its effects. Study Design: We conducted a comprehensive search across databases, including PubMed, PMC, Cochrane, EuroPMC, and ctri.gov.in to identify pertinent articles. Our focus was solely on published animal studies examining Lupeol's anti-cancer effects, with reviewers independently assessing bias risk and resolving discrepancies through consensus. Result: 20 studies were shortlisted. The results demonstrated that Lupeol brings changes in the tumor volume by [Hedges's g: -6.62; 95 % CI: -8.68, -4.56; tau(2): 24.36, I-2: 96.50 %; p < 0.05] and tumor weight by [Hedges's g: -3.97; 95 % CI: -5.20, -2.49; tau(2): 2.70, I-2: 79.27 %; p <0.05]. The high I-2, negative Egger's value, and asymmetrical funnel plot show the publication bias among the studies. Further, Lupeol in combination with other chemotherapeutic agents showed better outcomes as compared to them alone [Hedges's g: -6.38; 95 % CI: -11.82, -0.94; tau(2): 46.91; I-2: 98.68 %; p <0.05]. Lupeol also targets various signaling molecules and pathways to exert an anti-cancer effect. Conclusion: In conclusion, Lupeol significantly reduces tumor volume and weight. Combining Lupeol with other chemotherapy agents shows promise for enhancing anti-cancer effects. However, high variability among studies and evidence of publication bias suggest caution in interpreting results.