Glabridin induces apoptosis and autophagy through JNK1/2 pathway in human hepatoma cells

Hsieh, Ming‐Ju; Chen, Mu‐Kuan; Chen, Chih‐Jung; Hsieh, Ming‐Chang; Lo, Yu‐Sheng; Chuang, Yi‐Ching; Chiou, Hui‐Ling; Yang, Shun‐Fa

doi:10.1016/j.phymed.2016.01.005

Cited by 48 publications

(38 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Glabridin also suppressed the cancer stem cell‐like properties by blocking the SMAD2 signaling pathway of human breast cancer and HCC cells . Previous studies have demonstrated that glabridin induces apoptosis through caspase‐9, −8, and −3 activation through the JNK1/2 pathways in human HCC and promyelocytic leukemia cells . These results are correspond with our reports, in which glabridin inhibited cancer cell proliferation and enhanced caspase activation through the JNK1/2 pathway.…”

Section: Discussionsupporting

confidence: 92%

“…Glabridin has been associated with numerous biological properties; it has antioxidant, anti‐inflammatory, antiatherosclerotic, cardiovascular protective, energy metabolism regulating, immunomodulatory, estrogenic, neuroprotective, antiosteoporotic, antinephritic, antibacterial, antifungal, antiobesity, radical scavenging, and skin‐whitening activities . Studies have indicated that glabridin has antitumor effects, including antiproliferation effects in liver and breast cancers; antimetastatic effects in liver, breast, and lung cancers; antiangiogenetic effects in breast and lung cancers; inhibitory effects on the cancer stem cell–like properties in breast and lung cancers; and antiapoptotic effects in leukemia and liver cancers. However, the effects of glabridin on human oral cancer apoptosis have not been evaluated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glabridin induces apoptosis and cell cycle arrest in oral cancer cells through the JNK1/2 signaling pathway

Chen

Hsieh

et al. 2018

Environmental Toxicology

Self Cite

View full text Add to dashboard Cite

Glabridin, a flavonoid extracted from licorice (Glycyrrhiza glabra), possesses various biological properties, including anticancer activities. However, the effect of glabridin on oral cancer cell apoptosis and the underlying molecular mechanisms has not been elucidated. In this study, we demonstrated that glabridin treatment significantly inhibits cell proliferation in human oral cancer SCC-9 and SAS cell lines. Flow cytometric assays demonstrated that glabridin induced several features of apoptosis, such as sub-G1 phase cell increase and phosphatidylserine externalization. Furthermore, glabridin induced apoptosis dose-dependently in SCC-9 cells through caspase-3, -8, and -9 activation and poly (ADP-ribose) polymerase cleavage. Moreover, glabridin increased the phosphorylation of the extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase (JNK) pathways in a dose-dependent manner. Moreover, the inhibition of the JNK1/2 inhibitor significantly reversed the glabridin-induced activation of the caspase pathway. In conclusion, our findings suggest that glabridin induces oral cancer cell apoptosis through the JNK1/2 pathway and is a potential therapeutic agent for oral cancer.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Glabridin induces apoptosis and cell cycle arrest in oral cancer cells through the JNK1/2 signaling pathway

Chen

Hsieh

et al. 2018

Environmental Toxicology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The dysregulation of autophagy is closely related to the occurrence, development, and metastasis of tumors, and excessive autophagy can also lead to cell death (Hsieh et al., ; C. Li, Wang, Wang, Yi, Li, & He, ). The presence of LC3 in autophagosomes and the transformation of LC3II are used as indicators of autophagy (Huang, Okamoto, Yu, & Sinicrope, ; Pankiv et al., ).…”

Section: Discussionmentioning

confidence: 99%

Effect of Alkylresorcinols on Autophagy, Migration, and Invasion of HepG2 Cells

Guo

Xiaoming

2019

Journal of Food Science

View full text Add to dashboard Cite

Alkylresorcinols are phenolic lipids that mainly exist in the cortex of grains, and they exhibit anticancer activity against various cancer cells in vitro. However, the underlying action mechanisms are still unclear. In our study, the influence of alkylresorcinols C19:0 and C21:0 (ARs) upon migration, invasion, and autophagy in human hepatoblastoma HepG2 cells was evaluated. Results showed that ARs at 80 and 160 µg/mL significantly suppressed cells proliferation, migration, and invasion, downregulated the expression of proteins RhoA and MMP‐7 associated with migration and invasion. ARs at 160 µg/mL, the rate of LC3 puncta was appreciably increased. After autophagy was blocked by 3‐MA or CQ, the expression of LC3II was significantly increased in 3‐MA+ARs group and p62 was significantly decreased in CQ+ARs group. The results indicate that ARs may promote autophagic flow. ARs (80, 160 µg/mL) significantly inhibited the expression of proteins p‐mTOR, p‐PI3K, and p‐Akt related to the PI3K/Akt pathway. The results of the present study suggest that ARs can activate autophagy and suppresses the biological behaviors of HepG2 cells by inhibiting the activation of MMP‐7, Rho/Rho‐associated protein kinase, and activation of the phosphatidylinositol 3‐kinase/Akt signaling pathway. Practical Application The anticancer mechanism of ARs in wheat bran was studied, which provided a basis for the development of anticancer functional auxiliary food with wheat bran as raw material. It is of great practical significance to promote the effective utilization of grain processing by‐products and improve the economic benefits of the grain industry.

show abstract

“…In general, the ERK cascade is activated by growth factors and is critical for proliferation and survival . In contrast, the p38 and JNK pathways are stimulated by genotoxic agents and apoptosis …”

Section: Introductionmentioning

confidence: 99%

Cantharidic acid induces apoptosis of human leukemic HL‐60 cells via c‐Jun N‐terminal kinase‐regulated caspase‐8/‐9/‐3 activation pathway

Wang

Chow

Chien

et al. 2018

Environmental Toxicology

Self Cite

View full text Add to dashboard Cite

Cantharidin, a natural toxin from blister beetles, has shown potent anticancer activities on many solid tumor cells. Recently, cantharidin and its analogue, norcantharidin, were also shown to suppress nonsolid tumors such as chronic myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However, there is no available information to address the effects of cantharidic acid (CAC), a hydrolysis product of cantharidin, on human AML cells. The present study showed that CAC, at a range of concentrations (0-20 μM), concentration-dependently inhibited cell proliferation in the HL-60 AML cell line. Western blot and flow cytometric assays demonstrated that CAC induced several features of apoptosis such as sub G1-phase cell increase, phosphatidylserine (PS) externalization, and significantly activated proapoptotic signaling including caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells. Moreover, treatment of HL-60 cells with CAC induced concentration- and time- dependent activation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Only JNK-, but not p38 MAPK-specific inhibitor can reverse the CAC-induced activation of the caspase-8, -9, and -3. We concluded that CAC can induce apoptosis in human leukemic HL-60 cells via a caspases-dependent pathway, and that the apoptosis-inducing effect of CAC can be regulated by JNK activation signaling.

show abstract

Glabridin induces apoptosis and autophagy through JNK1/2 pathway in human hepatoma cells

Cited by 48 publications

References 47 publications

Glabridin induces apoptosis and cell cycle arrest in oral cancer cells through the JNK1/2 signaling pathway

Glabridin induces apoptosis and cell cycle arrest in oral cancer cells through the JNK1/2 signaling pathway

Effect of Alkylresorcinols on Autophagy, Migration, and Invasion of HepG2 Cells

Cantharidic acid induces apoptosis of human leukemic HL‐60 cells via c‐Jun N‐terminal kinase‐regulated caspase‐8/‐9/‐3 activation pathway

Contact Info

Product

Resources

About