Abstract
Background/Objectives: Cancer has been associated with significant morbidity and mortality worldwide, particularly related to chemotherapy resistance. Therefore, it is essential to investigate alternative sources of non-toxic antitumor compounds. The cactus Lophocereus marginatus is native to Mexico and is commonly used to treat gastrointestinal infections and diabetes in traditional medicine. Methods: The in vitro antitumor activity of L. marginatus extract fractions against murine L5178Y-R lymphoma cells was evaluated. The crude extract and its solvent-derived fractions were evaluated for cytotoxicity, selectivity, and hemolytic activity. Results: The crude extract exhibited an IC(50) of 9.09 μg/mL, demonstrating a high selectivity index (SI: 330.03), with no hemolytic activity observed at 1000 μg/mL. The LM-HP, LM-CP, and LM-MP partitions showed varying IC(50) values (6.74, 7.93, and 45.38 μg/mL, respectively) and selectivity indices of 445.1, 378.31, and 66.1, respectively. Only LM-HP induced hemolysis at 200 μg/mL. The most promising fraction, CP-F8, exhibited an IC(50) of 11.2 μg/mL, high selectivity index (354.29), and antioxidant activity, without hemolytic effects. Phytochemical analysis of CP-F8 identified phenolic compounds, triterpenes, and sterols, which are known for their anti-cancer and anti-inflammatory properties. In vivo tests showed no significant liver damage or changes in body weight, indicating the safety of CP-F8. Conclusions: These results suggest that CP-F8 is a promising antitumor candidate with selective cytotoxicity and minimal toxicity to normal cells.