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Quinalizarin (Quina) is one of the main components of many herbal medicines and has good anti-tumor activity. However, the exact mode of cytotoxic action and signaling pathways on Quina in human esophageal cancer has not yet been confirmed. In this study, we explored the anticancer effect of Quina against human esophageal cancer HCE-4 cells and the underlying mechanisms. The results of the Cell Counting Kit-8 (CCK-8) assay showed that Quina inhibited the viability of human esophageal cancer HCE-4 cells in a dose-dependent and time-dependent manner. It also inhibited HCE-4 cells proliferation and induced apoptosis by increasing the levels of Bad, caspase-3, and PARP, decreasing the level of Bcl-2. The results of the cell cycle analysis suggested that Quina arrested HCE-4 cells in the G0/G1 cycle by downregulating cyclin-dependent (CDK) 2/4, cyclin D1/E and upregulating the levels of p21 and p27. We also found that Quina activated mitogen-activated protein kinase (MAPK) and inhibited the signal transducer and activator of transcription-3 (STAT3) and nuclear factor kappa B (NF-κB) signaling pathways. Furthermore, Quina significantly increased intracellular reactive oxygen species (ROS) level. The pretreatment of N-acetyl-L-cysteine (NAC) blocked the apoptosis induced by Quina and inhibited the activities of MAPK, STAT3, and NF-κB signaling pathways. These results indicate that Quina induces the apoptosis in HCE-4 cells, which is via accumulating ROS generation and regulating MAPK, STAT3, and NF-κB. In conclusion, this study demonstrated that Quina have good therapeutic effects on human esophageal cancer cells.

The present study investigated the mechanisms of apoptosis induced by cryptotanshinone (CT) in human rheumatoid arthritis fibroblast‑like synoviocytes (RA‑FLSs). Cell Counting kit‑8 assay was performed to determine the cytotoxic effects of CT in human RA‑FLSs, including primary RA‑FLS, HFLS‑RA and MH7A cells, and in HFLS cells derived from normal synovial tissue. Annexin V‑FITC/PI staining was used to detect the apoptotic effects of CT in HFLS‑RA and MH7A cells. Flow cytometry was performed to detect the apoptotic and reactive oxygen species (ROS) levels induced by CT in HFLS‑RA cells. Western blotting was used to assess the expression levels of proteins associated with apoptosis and with the mitogen‑activated protein kinase (MAPK), protein kinase B (Akt), and signal transducer and activator of transcription‑3 (STAT3) signaling pathways. The results demonstrated that CT treatment significantly suppressed HFLS‑RA and MH7A cell growth, whereas no clear inhibitory effect was observed in normal HFLS cells. CT exposure downregulated the expression levels of B‑cell lymphoma 2 (Bcl‑2), p‑Akt, p‑extracellular signal‑related kinase and p‑STAT3, while it upregulated the expression levels of Bcl‑2‑associated death promoter (Bad), caspase‑3, poly (ADP‑ribose) polymerase (PARP), p‑p38 and p‑c‑Jun N‑terminal kinase. Following ROS scavenging, the CT‑induced apoptosis and altered expression levels of Bcl‑2, Bad, cleaved caspase‑3 and cleaved PARP were restored. Furthermore, the Akt, MAPK and STAT3 signaling pathways were regulated by intracellular ROS. These results suggest that ROS‑mediated Akt, MAPK and STAT3 signaling pathways serve important roles in the CT‑induced apoptosis of RA‑FLSs.

Derivatives of 1,4‑naphthoquinone have excellent anti‑cancer effects, but their use has been greatly limited due to their serious side effects. To develop compounds with decreased side effects and improved anti‑cancer activity, two novel types of 1,4‑naphthoquinone derivatives, 2,3‑dihydro‑2,3‑epoxy‑2‑propylsulfonyl‑5,8‑dimethoxy‑1,4‑naphthoquinone (EPDMNQ) and 2,3‑dihydro‑2,3‑epoxy‑2‑nonylsulfonyl‑5,8‑dimethoxy‑1,4‑naphthoquinone (ENDMNQ) were synthesized and their anti‑tumor activities were investigated. The effects of EPDMNQ and ENDMNQ on cell viability, apoptosis and accumulation of reactive oxygen species (ROS) in liver cancer cells were determined by MTT cell viability assay and flow cytometry. The expression levels of mitochondrial, mitogen activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathway‑associated proteins in Hep3B liver cancer cells were analyzed by western blot analysis. The results demonstrated that EPDMNQ and ENDMNQ inhibited the proliferation of liver cancer Hep3B, HepG2, and Huh7 cell lines but not that of normal liver L‑02, normal lung IMR‑90 and stomach GES‑1 cell lines. The number of apoptotic cells and ROS levels were significantly increased following treatment with EPDMNQ and ENDMNQ, and these effects were blocked by the ROS inhibitor N‑acetyl‑L‑cysteine (NAC) in Hep3B cells. EPDMNQ and ENDMNQ induced apoptosis by upregulating the protein expression of p38 MAPK and c‑Jun N‑terminal kinase and downregulating extracellular signal‑regulated kinase and STAT3; these effects were inhibited by NAC. The results of the present study demonstrated that EPDMNQ and ENDMNQ induced apoptosis through ROS‑modulated MAPK and STAT3 signaling pathways in Hep3B cells. Therefore, these novel 1,4‑naphthoquinone derivatives may be useful as anticancer agents for the treatment of liver cancer.

Quinalizarin may be a potential chemical agent for cancer therapy, as it exerts anti‑tumour effects against a variety of different types of cancer. However, the underlying regulatory mechanism and signalling pathways of quinalizarin in lung cancer cells remains unknown. The present study sought to investigate the effects of quinalizarin on proliferation, apoptosis and reactive oxygen species (ROS) generation in lung cancer. MTT assays were used to evaluate the effects of quinalizarin on the viability of lung cancer A549, NCI‑H460 and NCI‑H23 cells. Flow cytometry was employed to evaluate the effects of quinalizarin on the cell cycle, apoptosis and ROS generation in A549 cells. Western blotting was performed to detect cell cycle and apoptosis‑associated protein expression levels in A549 cells. Quinalizarin inhibited A549, NCI‑H460 and NCI‑H23 cell proliferation and induced A549 cell cycle arrest at the G0/G1 phase. Quinalizarin induced apoptosis by upregulating the expression of B‑cell lymphoma 2 (Bcl‑2)‑associated agonist of cell death, cleaved‑caspase‑3 and cleaved‑poly (adenosine diphosphate‑ribose) polymerase, and downregulating the expression of Bcl‑2. Furthermore, quinalizarin activated mitogen‑activated protein kinase (MAPK) and p53, and inhibited the protein kinase B and signal transducer and activator of transcription‑3 (STAT3) signalling pathways. In addition, quinalizarin increased ROS generation. The ROS scavenger N‑acetyl‑L‑cysteine restored quinalizarin‑induced cell apoptosis, and inactivated the MAPK and STAT3 signalling pathways. The results of the present study demonstrated that quinalizarin induces G0/G1 phase cell cycle arrest and apoptosis via ROS mediated‑MAPK and STAT3 signalling pathways.