Current research in toxicology · 2026
Effects of the combination of brefeldin A and tunicamycin on endoplasmic reticulum stress and apoptosis in human normal hepatocytes.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yang Ying, Hou Minfei, Li Minghong, Duan Mengyi, Hao Yuchao, Zhao Yifan, Ji Xiaotong, Bai Jianying
Аннотация
BACKGROUND: Due to its ability to inhibit the growth of hepatoma cells, brefeldin A (BFA) has been considered a promising drug candidate for liver cancer. However, there is limited research on its safety profile and potential impacts when administered alone or in combination with other anticancer drugs.
OBJECTIVE: To evaluate the safety of BFA in combination with tunicamycin (TM, a candidate anticancer drug) in human normal liver cells (HL-7702) in terms of its ability to induce endoplasmic reticulum (ER) stress and apoptosis.
METHODS: HL-7702 cells were exposed to BFA (0-2.5 mg/L) and TM (0-5 mg/L), either alone or in combination, for 24 h. Cell viability was measured using the CCK-8 assay, and apoptotic rates were determined using flow cytometry. The mRNA and protein levels of key factors related to cell proliferation, ER stress, and apoptosis were determined using quantitative RT-PCR and Western blot, respectively.
RESULTS: BFA and TM, either alone or in combination, significantly reduced the viability of HL-7702 cells. BFA alone and BFA + TM combination could weakly induce apoptosis, increase the expression of caspase 12, and reduce the protein level of proliferating cell nuclear antigen (PCNA). BFA alone and BFA + TM combination could significantly increase the mRNA and protein levels of binding immunoglobulin protein (BiP) and activating transcription factor 4 (ATF4), but did not affect the mRNA and protein levels of C/EBP homologous protein (CHOP) and poly (ADP-ribose) polymerase-1 (PARP-1).
CONCLUSION: This study demonstrates that BFA, alone and in combination with TM, exerts mild pro-apoptotic effects on HL-7702 cells, independent of the CHOP and caspase-3 pathways. These findings underscore the necessity of evaluating the potential hepatotoxicity of BFA-based therapies, particularly in combination treatments, to ensure their safe clinical application.
OBJECTIVE: To evaluate the safety of BFA in combination with tunicamycin (TM, a candidate anticancer drug) in human normal liver cells (HL-7702) in terms of its ability to induce endoplasmic reticulum (ER) stress and apoptosis.
METHODS: HL-7702 cells were exposed to BFA (0-2.5 mg/L) and TM (0-5 mg/L), either alone or in combination, for 24 h. Cell viability was measured using the CCK-8 assay, and apoptotic rates were determined using flow cytometry. The mRNA and protein levels of key factors related to cell proliferation, ER stress, and apoptosis were determined using quantitative RT-PCR and Western blot, respectively.
RESULTS: BFA and TM, either alone or in combination, significantly reduced the viability of HL-7702 cells. BFA alone and BFA + TM combination could weakly induce apoptosis, increase the expression of caspase 12, and reduce the protein level of proliferating cell nuclear antigen (PCNA). BFA alone and BFA + TM combination could significantly increase the mRNA and protein levels of binding immunoglobulin protein (BiP) and activating transcription factor 4 (ATF4), but did not affect the mRNA and protein levels of C/EBP homologous protein (CHOP) and poly (ADP-ribose) polymerase-1 (PARP-1).
CONCLUSION: This study demonstrates that BFA, alone and in combination with TM, exerts mild pro-apoptotic effects on HL-7702 cells, independent of the CHOP and caspase-3 pathways. These findings underscore the necessity of evaluating the potential hepatotoxicity of BFA-based therapies, particularly in combination treatments, to ensure their safe clinical application.