Combination of Curcumin and Silibinin Exhibits Anti-Tumorigenic Activity Against Colon Cancer in a Xenograft Animal Model, Causing Cell Death by Increased ROS, Activation of AMPK, and Inhibition of mTORC1
Year: 2026
Type: preprint
Abstract: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States and has a high prevalence in both men and women. Current methods of treatment for CRC include chemotherapy and radiotherapy; however, long periods of exposure to either of these treatment methods are detrimental to one’s overall health. Phytochemicals have been used as natural, non-toxic therapeutic agents against various cancers, suggesting they could be a potential novel treatment for cancers with fewer or no side effects. Curcumin is the bioactive component of Curcuma longa, or turmeric, and is known for its anti-inflammatory, antioxidant, and anti-cancer properties. Several studies have shown that curcumin exhibits anticancer activity through multiple key signaling pathways. Another phytochemical, silibinin B, is the major bioactive component of silymarin, which is present in Silybum marianum (milk thistle). Silibinin B has been used as a treatment for hepatic diseases and has also shown promising results as a chemopreventative agent. Silibinin B exhibits anticancer activity against various cancer types. Previously, using an in vitro model, we demonstrated that combinatorial treatment with curcumin and silymarin (CS), that contains all seven phytochemicals from milk thistle, synergistically increased CRC cell death compared with single-compound treatment. In our current study, we used a xenograft mouse model to evaluate the efficacy of curcumin alone, silibinin B alone, and their combination against tumors induced by the colorectal cancer cell line DLD-1. We observed that the combination treatment significantly reduced tumor growth compared to either compound alone. Furthermore, the combination treatment induced significantly higher levels of tumor cell apoptosis than the single-compound treatments. To understand how CS reduces tumor burden , we treated DLD‑1 cells with the agents singly or in combination. CS‑treated cells exhibited a significant increase in reactive oxygen species (ROS) levels. We also found that elevated ROS activated AMPK, which in turn inhibited the mTORC1 pathway. The combined effects of increased ROS and mTORC1 inhibition create a “double hit” that may promote cancer cell death.
Source: Preprints.org
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7203725364