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D-Limonene Exhibits Antiproliferative Activity Against Human Colorectal Adenocarcinoma (Caco-2) Cells via Regulation
1Department of Biology, Faculty of Science, Al-Baha University, Al-Baha 65779, Saudi Arabia.
Abstract:
Current therapies for colorectal cancer (CRC) are associated with significant side effects and limitations, driving the search for novel therapeutic approaches. This study investigated the antiproliferative potential of D-limonene, a natural compound, on human colorectal adenocarcinoma (Caco-2) cells and analyzed its underlying mechanisms. Caco-2 cells were treated with D-limonene or doxorubicin (DOX) for 24 h. Cell viability was assessed using the MTT assay, with D-limonene and DOX showing IC50 values of 18.6 and 6.4 µM, respectively. In comparison to controls, D-limonene treatment dramatically enhanced the formation of reactive oxygen species (ROS) and decreased cellular antioxidant capacity, as seen by concentration-dependent lower glutathione (GSH) levels. The substance also increased the levels of pro-apoptotic proteins (caspase-3, Bax), tumor suppressor p53, lactate dehydrogenase (LDH), and inflammatory indicators [tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)]. Furthermore, in a concentration-dependent way, D-limonene therapy decreased the levels of matrix metalloproteinases (MMP2, MMP9), proliferation marker Ki67, and the anti-apoptotic protein Bcl-2. These results imply that the induction of oxidative stress, inflammation, and apoptotic pathways mediates D-limonene's antiproliferative actions in colon cancer cells. Our findings show that D-limonene has therapeutic promise as a natural substitute for the treatment of colorectal cancer.
Insights
D-limonene, a natural compound, shows significant antiproliferative effects on colon cancer cells by inducing oxidative stress and apoptosis. This suggests D-limonene
Area of Science:
- Oncology
- Natural Product Chemistry
- Cell Biology
Background:
- Colorectal cancer (CRC) therapies have limitations and side effects.
- There is a need for novel therapeutic strategies for CRC.
- D-limonene is a natural compound with potential therapeutic applications.
Purpose of the Study:
- To investigate the antiproliferative effects of D-limonene on human colorectal adenocarcinoma (Caco-2) cells.
- To elucidate the underlying mechanisms of D-limonene's action.
- To evaluate D-limonene as a potential natural alternative for CRC treatment.
Main Methods:
- Caco-2 cells were treated with D-limonene or doxorubicin (DOX).
- Cell viability was assessed using MTT assay.
- Levels of reactive oxygen species (ROS), glutathione (GSH), apoptotic proteins (caspase-3, Bax, Bcl-2), p53, LDH, inflammatory markers (TNF-α, IL-1β), MMP2, MMP9, and Ki67 were analyzed.
Main Results:
- D-limonene exhibited antiproliferative activity with an IC50 of 18.6 µM.
- D-limonene increased ROS production and decreased GSH levels, indicating oxidative stress.
- D-limonene modulated apoptotic and inflammatory pathways and reduced proliferation markers.
Conclusions:
- D-limonene's antiproliferative effects are mediated by oxidative stress, inflammation, and apoptosis induction.
- D-limonene demonstrates therapeutic promise as a natural agent for colorectal cancer.
- Further research into D-limonene for CRC treatment is warranted.
