d -Limonene

Chaudhary et al. have provided interesting data in their recent article. ¹ Interestingly, recent data suggest that d-limonene attenuates tumor growth in a number of other systemic malignancies besides its inhibitory effect on skin tumorogenesis.

For instance, inhibition of tumor proliferation is also seen in colorectal malignancies. It mediates this role in part by augmenting Bax levels, while at the same time, it attenuates Bcl-2 levels. In addition, it increases poly(ADP-ribose) polymerase cleavage within the cancerous cells. ² Vascular endothelial growth factor (VEGF) inhibition accompanies the above changes. It also has an inhibitory effect on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, while at the same time, it activates caspase 9. These changes result in marked increase in intratumoral apoptosis and also attenuate tumoral angiogenesis. ³ Matrix metallopeptidase-9 expression is also downregulated. These effects are dose dependent.

Attenuation of tumor growth is also seen in gastric malignancies. It mediates its antineoplastic effects by markedly attenuating intratumoral angiogenesis. At the same time, tumoral apoptosis is significantly enhanced. Protein 53 or tumor protein 53 (p53) levels are upregulated. ⁴ Metastasis from the primary gastric tumor is also decreased significantly. VEGF expression is downregulated resulting in decreased microvascular density. Bcl-2 levels are also downregulated at the same time. In addition, d-limonene augments the antineoplastic effects of other chemotherapeutic agents such as 5-fluorouracil. ⁵

It is obvious from the above examples that d-limonene has significant proapoptotic and antiangiogenesis effects. Further research is needed to fully harness its antineoplastic effects.