Aloe vera Enhanced Hydroxycamptothecin‐Mediated Antitumor Activity in Colorectal Carcinoma Based on the Targeted Regulation of Nucleotide Metabolism

ABSTRACT Introduction Colorectal cancer (CRC) remains one of the leading causes of cancer‐related mortality worldwide. Combination therapies, which integrate traditional Chinese medicine (TCM) with conventional chemotherapeutic agents, offer a promising new strategy for the management of CRC. Objective This study aimed to investigate the potential of Aloe vera (L.) Burm.f. ( A. vera ) as an adjuvant to hydroxycamptothecin (HCPT) for CRC treatment and to explore the underlying mechanisms, specifically focusing on nucleotide metabolism, as perturbations in intracellular nucleotide pools are closely linked to various human pathologies. Methods The aqueous extract of A. vera adjuvantly ameliorated the progression of colon carcinogenesis was investigated in Apc Min/+ mouse model. For the underlying mechanism studies, cytotoxicity assessment, DNA damage, cell cycle, RNA and DNA synthesis analysis, endogenous nucleotides determination, and Western blot were performed in HCT 116 cells. Results Major constituents of A. vera , including aloin A, aloin B, aloesin, aloenin, and aloe‐emodin, were quantified and found to meet Chinese Pharmacopoeia standards. A. vera synergistically enhanced the anticancer activity of HCPT. This effect was mediated by exacerbated DNA damage, imbalanced purine/pyrimidine metabolism, and inhibition of the Wnt/β‐catenin signaling pathway. Conclusion This study provided preliminary evidence that A. vera could be developed as an adjuvant therapy for CRC, contributing to its further clinical application in this field.