Quinalizarin induces cycle arrest and apoptosis via reactive oxygen species‐mediated signaling pathways in human melanoma A375 cells

Abstract

Quinalizarin, a bioactive and highly selective compound, is known to promote apoptosis in colon and lung cancer cells. However, studies evaluating quinalizarin‐induced apoptosis in melanoma cells have not been conducted. In the present study, we investigated the underlying mechanisms of antimelanoma activity of quinalizarin in human melanoma A375 cells. The MTT assay and Trypan blue staining were used to evaluate the cell viability. The flow cytometry was used to detect cell cycle, apoptosis and reactive oxygen species (ROS). Western blot was used to detect the expression of cell cycle and apoptosis‐related proteins, MAPK, and STAT3. The results revealed a significant dose and time dependent effect of quinalizarin on inhibiting proliferation in three kinds of human melanoma cells, and had no significant toxic effects on normal cells. Moreover, quinalizarin triggered G2/M phase cell arrest by modulating the protein expression levels of CDK 1/2, cyclin A, cyclin B, p21 and p27, and induced apoptosis by down‐regulating the antiapoptotic protein Bcl‐2 and upregulating the proapoptotic protein BAD, leading to the activation of caspase‐3 and PARP in the caspase cascade in A375 cells. Quinalizarin treatment led to apoptosis of A375 cells via activation of MAPK and inhibition of STAT3 signaling pathways. In addition, quinalizarin increased the level of ROS, but ROS scavenger NAC inhibited quinalizarin‐induced apoptosis by regulating MAPK and STAT3 signaling pathways. In summary, quinalizarin induces cell cycle arrest and apoptosis via ROS‐mediated MAPK and STAT3 signaling pathways in human melanoma A375 cells, and quinalizarin may be used as a novel and effective antimelanoma therapeutic.

Molecular mechanisms of quinalizarin induces apoptosis and G0/G1 cell cycle of human esophageal cancer HCE‐4 cells depends on MAPK, STAT3, and NF‐κB signaling pathways

“…Many studies have reported that anthraquinone components affect the cell differentiation, migration, and apoptosis of various genetic and pathological types of human cancer cell lines 26,27 . Similarly, as one type of anthraquinone, Quina inhibits the proliferation and accelerates apoptosis of different human tumor cells 28,29 . In the current study, we demonstrated the effects of Quina on human esophageal cancer cell proliferation, apoptosis, and cell cycle distribution.…”

“…26,27 Similarly, as one type of anthraquinone, Quina inhibits the proliferation and accelerates apoptosis of different human tumor cells. 28,29 In the current study, we demonstrated the effects of Quina on human esophageal cancer cell proliferation, apoptosis, and cell cycle distribution. In particular, we studied the effects of Quina on the survival and growth of the human esophageal cancer HCE-4 cells in vitro and showed that it obviously inhibited the proliferation of HCE-4 cells.…”

Molecular mechanism, regulation, and therapeutic targeting of the STAT3 signaling pathway in esophageal cancer (Review)

“…Some natural compounds can directly target STAT3. Quinalizarin, also known as 1,2,5,8-tetrahydroquinone, is a dual anthraquinone compound derived from the roots of the Rubiaceae herb ( 201 ). Quinalizarin is a compound found in several herbal remedies that have anti-tumor properties.…”

Design, Synthesis and Biological Activity Testing of Library of Sphk1 Inhibitors

“…Melanoma, also known as malignant melanoma, is a malignant tumor caused by abnormally rapid proliferation of melanocytes [ 15 ]. It is more common in skin, pia meninga, choroid and other parts of the eye [ 16 ].…”

“…Damage or over activation of certain components of these pathways may lead to malignant transformation and the development of cancer. In the present study, we consider that signaling pathways such as cyclin/CDK, Ras/Raf/MEK/MAPK [ 19 ], JNK/C-Jun/AP-1, PI3K/Akt/PTEN/mTOR [ 20 ], IKK/I-κB/NF-κB [ 21 ], Wnt/β-catenin [ 22 ], Notch, Jak/STAT [ 15 ], MITF and some growth factors regulate the cycle progression, apoptosis and development of melanoma cells. However, no ideal inhibitor has appeared thus far, and there are still no inhibitors approved for marketing.…”