Licochalcone A-Induced Apoptosis Through the Activation of p38MAPK Pathway Mediated Mitochondrial Pathways of Apoptosis in Human Osteosarcoma Cells In Vitro and In Vivo

Abstract

Background: Licochalcone A (LicA) is isolated from the roots of Glycyrrhiza glabra and possesses antitumor and anti-invasive activities against several tumor cells. However, the antitumor effects of LicA on human osteosarcoma cells have yet to be demonstrated either in vitro or in vivo. Methods: Cell viability was measured by MTT assay. Apoptosis and mitochondrial dysfunction were detected with Annexin V/PI staining and JC-1 staining by flow cytometry. The expressions of caspase- or mitochondrial-related proteins were demonstrated by western blotting. Antitumor effect of LicA on 143B xenograft mice in vivo. Results: LicA could inhibit cell proliferation and induce apoptosis in human osteosarcoma cells, as evidenced by a decrease in cell viability, loss of mitochondrial membrane potentials, and activation of caspases. LicA treatment substantially reduced the expression of Bcl-2 and Mcl-1 and increased the expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, and Bax in HOS and U2OS cells. Moreover, mitochondrial membrane potential and apoptosis suppression mediated by Z-VAD or tauroursodeoxycholic acid significantly reduced LicA-induced mitochondria-dependent apoptosis. The study also determined that LicA treatment induced p38MAPK phosphorylation, but siRNA-p38 or BIRB796 substantially reversed cell viability through the inhibition of mitochondria-dependent apoptosis pathways. Finally, an in vivo study revealed that LicA significantly inhibited 143B xenograft tumor growth. Conclusions: These findings demonstrate that LicA has antitumor activities against human osteosarcoma cells through p38MAPK regulation of mitochondria-mediated intrinsic apoptotic pathways in vitro and in vivo.

Potential Antimetastatic Effect of Timosaponin AIII against Human Osteosarcoma Cells through Regulating the Integrin/FAK/Cofilin Axis

“…Cell culture was performed as described in a previous study [ 41 ]. Human 143-B and HOS osteosarcoma cell lines were kindly provided by Prof. Shun-Fa Yang (Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan).…”

Triggering of Apoptosis in Osteosarcoma 143B Cell Line by Carbon Quantum Dots via the Mitochondrial Apoptotic Signal Pathway

“…High levels of radiation cause excessive activation of PARP-1, and this high level of PARP-1 can activate release of apoptosis-inducing factor (AIF). AIF is transferred from the cytoplasm to the nucleus and can promote DNA fragmentation and chromatin aggregation in the nucleus, resulting in apoptosis [37,38].…”

Calycosin induces apoptosis via p38‑MAPK pathway‑mediated activation of the mitochondrial apoptotic pathway in human osteosarcoma 143B cells

“…Other findings have demonstrated that calycosin can inhibit growth and induce apoptosis in breast cancer cells via estrogen receptor β-dependent regulation of the insulin-like growth factor 1 receptor, p38 MaPK and Pi3K/akt pathways in breast cancer cells (15). In vitro and in vivo research demonstrated that licochalcone a regulated the mitochondrial-mediated internal apoptotic pathway via p38-MaPK, and exerted antitumor effects on human osteosarcoma cells (28). Similarly, the present study suggested that calycosin increased p-p38-MaPK expression, whereas a specific p38 inhibitor, BIRB 796, significantly reversed the effects of calycosin treatment on the viability, caspase expression, MMP and apoptotic rate of osteosarcoma 143B cells.…”

“…The role of p38-MAPK in cell proliferation and apoptosis has been extensively investigated ( 27 ). Accumulating evidence has suggested that the role of p38-MAPK is controversial in several tumor cells, and the variation may be associated with the applied stimuli and duration, as well as the specific characteristics and types of cells ( 28 ). The evidence revealed that NK007 induces G1/S cell cycle arrest by promoting p38-MAPK phosphorylation and suppressing the expression of hexokinase2, which is associated with acidification and oxygen consumption in ovarian cells ( 29 ).…”