Cytotoxic and apoptotic effects of leptocarpin, a plant-derived sesquiterpene lactone, on human cancer cell lines

• Leptocarpin exhibits cytotoxicity against different cancer cell lines.
• The IC50 values are similar to those reported for other sesquiterpene lactones.
• Leptocarpin induces apoptosis by activating the mitochondrial pathway.
• It is shown that leptocarpin is also a potent inhibitor of NF-κB activation.
• These results indicate that leptocarpin could be used as anticancer agent.

Sesquiterpene lactones have attracted much attention in drug research because they present a series of biological activities such as anticancer, antifungal, anti-inflammatory, antimicrobial and antioxidant. Leptocarpin (LTC) is a sesquiterpene lactone isolated from a native Chilean plant, Leptocarpha rivularis, which has been widely used in traditional medicine by Mapuche people. Previous work has demonstrated that LTC decreases cell viability of cancer cell lines. In this contribution, we analyze the mechanism of LTC cytotoxicity on different cancer cell lines. The results show that in all cases LTC induces an apoptotic process and inhibition of NF-κB. Apoptosis has been confirmed by observing condensation of chromatin, nuclear fragmentation, release of cytochrome c into the cytosol, and increasing of caspase-3 activity. It has also been found that LTC is an effective inhibitor of NF-κB, which suggests that leptocarpin-induced cytotoxicity involves in some degree the inhibition of NF-κB signaling pathway. The concentration at which LTC inhibits NF-κB activity to the control level is similar or even lower than that found for parthenolide and others sesquiterpene lactones. These results indicate that leptocarpine is a very interesting molecule that could be considered as therapeutic agent for cancer treatment.

Figure optionsDownload as PowerPoint slide