Photo-activated pheophorbide-a, an active component of Scutellaria barbata, enhances apoptosis via the suppression of ERK-mediated autophagy in the estrogen receptor-negative human breast adenocarcinoma cells MDA-MB-231

Aim of the study

Scutellaria barbata is a traditional Chinese medicine for cancer treatments. Pheophorbide-a (Pa), one of the active components isolated from this herbal medicine has been proposed to be a potential natural photosensitizer for photodynamic therapy. The anti-tumor effect of pheophorbide-a based photodynamic therapy (Pa-PDT) has been successfully demonstrated in a wide range of human malignant cell lines. However, the effectiveness of Pa-PDT has not yet been evaluated on human breast cancer, which is documented as the second common and the fifth most lethal cancer worldwide.

Materials and methods

The cytotoxicity of Pa-PDT was evaluated by using an estrogen receptor (ER)-negative human breast adenocarcinoma cell line MDA-MB-231. The involvement of mitochondria was revealed by the change of mitochondrial membrane potential and the increase of intracellular reactive oxygen species (ROS). The hallmarks of apoptosis, ER stress and autophagy were also assessed by DNA fragmentation, Western blotting, and immunostaining assays.

Results

Pa-PDT showed inhibitory effect on the growth of MDA-MB-231 cells with an IC₅₀ value of 0.5 μM at 24 h. Mitogen-activated protein kinase (MAPK) pathway was found to be triggered, where activation of c-Jun N-terminal kinase (JNK) and inhibition of extracellular signal-regulated kinase (ERK) were occurred in the Pa-PDT-treated cells. Our findings suggested that Pa-PDT exhibited its anti-tumor effects by the activation of mitochondria-mediated apoptosis and the ERK-mediated autophagy in MDA-MB-231 cells.

Conclusion

The present study suggested Pa-PDT is a potential protocol for the late phase human breast cancer, and it is the first study to demonstrate the Pa-PDT induced autophagy contributed to the anti-tumor effects of Pa-PDT on human cancer cells.