Study of the Cytotoxic and Antitumor Effect of L‐lysine‐α‐oxidase from Trichoderma harzianum Rifai

Background/Aim: Enzymatic anticancer therapies are actively investigated as they can selectively deprive cancer cells of essential nutrients. L‑lysine‑α‑oxidases of different origins have been reported as potential anticancer enzymes with a significant antitumor potency. This study aimed to evaluate the cytotoxic and antitumor activity of L‑lysine‑α‑oxidase obtained from the domestic strain of Trichoderma harzianum Rifai VKPM F‑180. Materials and Methods: The melanoma cell line A875 and normal keratinocytes HaCaT were used for cytotoxicity testing. Murine solid tumors sarcoma 45, carcinosarcoma W‑256, carcinoma PC‑1 and hepatoma 22 were used for experiments with animals. Tumor growth inhibition (TGI) was the primary measure of antitumor efficacy. Results: L‑lysine‑α‑oxidase exhibited selective cytotoxicity toward melanoma cells (IC50=0.09 μg/ml) compared to HaCaT cells (IC50=0.38 μg/ml). In animal models, the enzyme significantly inhibited growth of sarcoma 45, carcinoma PC‑1, and hepatoma 22, with TGI ranging from 25% to 41% at 35 U/kg by the 8th or 9th day post‑treatment. However, carcinosarcoma W‑256, a reactive oxygen species‑producing tumor, demonstrated lower sensitivity, particularly at higher enzyme doses. Conclusion: L‑lysine‑α‑oxidase from Trichoderma harzianum Rifai demonstrates promising selective cytotoxicity and antitumor activity, especially in ROS‑sensitive tumors. © 2025 Elsevier B.V., All rights reserved.