Abstract Objective To examine UVB-induced responses in normal human keratinocytes （HaCaT） and epidermoid carcinoma cells （A431） at the cellular and molecular level, and investigated the protective effect of salidr...Abstract Objective To examine UVB-induced responses in normal human keratinocytes （HaCaT） and epidermoid carcinoma cells （A431） at the cellular and molecular level, and investigated the protective effect of salidroside. Methods Cells irradiated by UVB at various dosage and their viability was assessed by MTT assays, cell cycle was analysed by flow cytometry. The expression of NF-KB, BCL-2, and CDK6 after 50 J/㎡ UVB irradiation were detected by RT-PCR and western blotting. Results Our results confirmed greater tolerance of A341 cells to UVB-induced damage such as cell viability and cell cycle arrest, which was accompanied by differential expression changes in NF-KB, BCL-2, and CDK6. UVB exposure resulted in HaCaT cells undergoing G1-S phase arrest. When treated with salidroside, HaCaT survival was significantly enhanced following exposure to UVB, suggesting great therapeutic potential for this compound. Conclusion Taken together, our study suggests that A431 respond differently to UVB than norma HaCaT cells, and supports a role for NF-KB, CDK6, and BCL-2 in UVB-induced cell G1-S phase arrest Furthermore, salidroside can effectively protect HaCaT from UVB irradiation.展开更多
Background Growing preclinical evidence shows that zoledronic acid （ZOL） exhibits direct antitumor activity in various cancer cell lines. However, the cytotoxic effects of ZOL on human hepatocellular carcinoma （HCC...Background Growing preclinical evidence shows that zoledronic acid （ZOL） exhibits direct antitumor activity in various cancer cell lines. However, the cytotoxic effects of ZOL on human hepatocellular carcinoma （HCC） cells have not been established. In the present study, we investigated the effect of ZOL on HCC both in vitro and in vivo. Methods Cytotoxicity and cell cycles were assessed with Sulforhodamine B colorimetric assay and flow cytometry. Expression levels of cell cycle phase-linked proteins were examined. The effect of ZOL on HCC in vivo was explored based on H22-subcutaneous injection （s.c.） and H22-intraperitoneal injection （i.p.） mice model. Results ZOL inhibited the growth of SK-HEP-1 and H22 cells and induced S-phase arrest through downregulating cdc2 protein and upregulating cyclin A. It inhibited the growth of s.c tumors, and increased the survival of both H22-s.c. and H22-i.p. mice in vivo. Conclusion ZOL inhibits qrowth of HCC cells in vitro and in vivo.展开更多
In an effort to understand the molecular events contributing to the cytotoxicity activity of resveratrol(RSV), we investigated its effects on human lung adenocarcinoma epithelial cell line A549 at different concentrat...In an effort to understand the molecular events contributing to the cytotoxicity activity of resveratrol(RSV), we investigated its effects on human lung adenocarcinoma epithelial cell line A549 at different concentrations. Cellular nucleoside metabolic profiling was determined by an established liquid chromatography-mass spectrometry method in A549 cells. RSV resulted in significant decreases and imbalances of deoxyribonucleoside triphosphates(d NTPs) pools suppressing subsequent DNA synthesis. Meanwhile, RSV at high concentration caused significant cell cycle arrest at S phase, in which cells required the highest dNTPs supply than other phases for DNA replication. The inhibition of DNA synthesis thus blocked subsequent progression through S phase in A549 cells,which may partly contribute to the cytotoxicity effect of RSV. However, hydroxyurea(HU), an inhibitor of RNR activity, caused similar dNTPs perturbation but no S phase arrest, finally no cytotoxicity effect. Therefore, we believed that the dual effect of high concentration RSV, including S phase arrest and DNA synthesis inhibition, was required for its cytotoxicity effect on A549 cells. In summary,our results provided important clues to the molecular basis for the anticancer effect of RSV on epithelial cells.展开更多
基金supported by the National Natural Science Foundation of China(30970673,81172634)Natural Science Foundation of Guangdong Province(9151022501000013,S2011040003686)+1 种基金Guangdong Province"211Project"(200826GW,201007GW)Grant from School of Public Health and Tropical Medicine of Southern Medical University,China(Grant No.GW201111)
文摘Abstract Objective To examine UVB-induced responses in normal human keratinocytes （HaCaT） and epidermoid carcinoma cells （A431） at the cellular and molecular level, and investigated the protective effect of salidroside. Methods Cells irradiated by UVB at various dosage and their viability was assessed by MTT assays, cell cycle was analysed by flow cytometry. The expression of NF-KB, BCL-2, and CDK6 after 50 J/㎡ UVB irradiation were detected by RT-PCR and western blotting. Results Our results confirmed greater tolerance of A341 cells to UVB-induced damage such as cell viability and cell cycle arrest, which was accompanied by differential expression changes in NF-KB, BCL-2, and CDK6. UVB exposure resulted in HaCaT cells undergoing G1-S phase arrest. When treated with salidroside, HaCaT survival was significantly enhanced following exposure to UVB, suggesting great therapeutic potential for this compound. Conclusion Taken together, our study suggests that A431 respond differently to UVB than norma HaCaT cells, and supports a role for NF-KB, CDK6, and BCL-2 in UVB-induced cell G1-S phase arrest Furthermore, salidroside can effectively protect HaCaT from UVB irradiation.
文摘Background Growing preclinical evidence shows that zoledronic acid （ZOL） exhibits direct antitumor activity in various cancer cell lines. However, the cytotoxic effects of ZOL on human hepatocellular carcinoma （HCC） cells have not been established. In the present study, we investigated the effect of ZOL on HCC both in vitro and in vivo. Methods Cytotoxicity and cell cycles were assessed with Sulforhodamine B colorimetric assay and flow cytometry. Expression levels of cell cycle phase-linked proteins were examined. The effect of ZOL on HCC in vivo was explored based on H22-subcutaneous injection （s.c.） and H22-intraperitoneal injection （i.p.） mice model. Results ZOL inhibited the growth of SK-HEP-1 and H22 cells and induced S-phase arrest through downregulating cdc2 protein and upregulating cyclin A. It inhibited the growth of s.c tumors, and increased the survival of both H22-s.c. and H22-i.p. mice in vivo. Conclusion ZOL inhibits qrowth of HCC cells in vitro and in vivo.
基金supported by the Macao Science and Technology Development Fund(FDCT,No.0052/2018/A2)
文摘In an effort to understand the molecular events contributing to the cytotoxicity activity of resveratrol(RSV), we investigated its effects on human lung adenocarcinoma epithelial cell line A549 at different concentrations. Cellular nucleoside metabolic profiling was determined by an established liquid chromatography-mass spectrometry method in A549 cells. RSV resulted in significant decreases and imbalances of deoxyribonucleoside triphosphates(d NTPs) pools suppressing subsequent DNA synthesis. Meanwhile, RSV at high concentration caused significant cell cycle arrest at S phase, in which cells required the highest dNTPs supply than other phases for DNA replication. The inhibition of DNA synthesis thus blocked subsequent progression through S phase in A549 cells,which may partly contribute to the cytotoxicity effect of RSV. However, hydroxyurea(HU), an inhibitor of RNR activity, caused similar dNTPs perturbation but no S phase arrest, finally no cytotoxicity effect. Therefore, we believed that the dual effect of high concentration RSV, including S phase arrest and DNA synthesis inhibition, was required for its cytotoxicity effect on A549 cells. In summary,our results provided important clues to the molecular basis for the anticancer effect of RSV on epithelial cells.
