Psoralen inhibits the proliferation and promotes apoptosis through endoplasmic reticulum stress in human osteosarcoma cells

Psoralen showed growth-inhibitory effects in osteosarcoma cells, and induced apoptosis via the ER stress pathway, which might be a potential drug to suppress the development of osteosarcoma.

Effects of psoralen (0-70 μg/mL) on the viability of two osteosarcoma cell lines cultured for 48 h was evaluated by MTT assays. The concentration of IC10 (8 μg/mL for MG-63 cells and 9 μg/mL for U2OS cells) was regarded to be a non-cytotoxic dose selected as the working concentration in the subsequent experiments. Effects of psoralen on cell proliferation for 48 h was assessed by colony formation assays. Flow cytometry analyses were performed to measure cell cycle and apoptosis. RT-qPCR and Western blotting were carried out to assess RNA expression and protein levels of endoplasmic reticulum (ER) stress associated factors.

Effects of psoralen (0-70 μg/mL) on the viability of two osteosarcoma cell lines cultured for 48 h was evaluated by MTT assays. The concentration of IC10 (8 μg/mL for MG-63 cells and 9 μg/mL for U2OS cells) was regarded to be a non-cytotoxic dose selected as the working concentration in the subsequent experiments. Effects of psoralen on cell proliferation for 48 h was assessed by colony formation assays. Flow cytometry analyses were performed to measure cell cycle and apoptosis. RT-qPCR and Western blotting were carried out to assess RNA expression and protein levels of endoplasmic reticulum (ER) stress associated factors.

Psoralen inhibited osteosarcoma cell viability (IC50 25 μg/mL for MG-63 cells and IC50 40 μg/mL for U2OS cells) in a dose-dependent manner and growth inhibition rate reached the highest level when cells were treated with 70 μg/mL psoralen. Psoralen induced cell cycle arrest in the G0/G1 phase and promoted apoptosis of both MG-63 and U2OS cells. The treatment of psoralen resulted in an increase in ATF-6 and CHOP protein levels as well as a decrease in Bcl-2 protein level, indicating that cell apoptosis induced by psoralen was associated with ER stress. Treatment with 4-PBA, the ER stress inhibitor, attenuated the ability of psoralen to promote apoptosis of MG-63 and U2OS cells. Conclusions: Psoralen showed growth-inhibitory effects in osteosarcoma cells, and induced apoptosis via the ER stress pathway, which might be a potential drug to suppress the development of osteosarcoma.