Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2
Аутори
Todorović, LidijaStamenković, Gorana
Vučetić-Tadić, Biljana
Umezawa, Kazuo
Božović, Ana M.
Yamashita, Shunichi
Stanojević, Boban
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The use of targeted inhibitors has shown promise as an effective approach in cancer therapy. However, targeted therapies based only on one drug, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), have limited success, partly because cancer cells engage alternate pathways for survival and proliferation. In the present study, we evaluated whether dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor ?B (NF-?B) inhibitor, can enhance the antitumor activities of 17-AAG, a 90 kDa heat shock protein (Hsp90) inhibitor, in the anaplastic thyroid cancer cell line KTC2. We examined the effect of combined drug treatment vs single drug treatment on cell survival. Isobologram analysis was performed to distinguish the additive vs synergistic effects of the drug combination. Western blotting was performed to investigate apoptosis markers: caspase 3, poly(ADP-ribose) polymerase-one (PARP-1), B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of... apoptosis 2 (cIAP-2). Compared to monotherapy, the combined treatment enhanced growth-inhibitory effects in a synergistic manner and strongly potentiated apoptosis. These results demonstrate the first in vitro evidence that a combination of Hsp90 and NF-?B inhibitors is a more effective modality for inhibiting cell proliferation and survival in anaplastic thyroid carcinoma cells than either agent alone, warranting further investigations.
Кључне речи:
combined treatment / Hsp90 inhibitor / NF-κB inhibitor / synergy / targeted inhibitorИзвор:
Archives of Biological Sciences, 2021, 73, 1, 31-38Финансирање / пројекти:
- Nagasaki University Global COE Program
DOI: 10.2298/ABS201010055T
ISSN: 0354-4664
WoS: 000631279700003
Scopus: 2-s2.0-85103483573
Институција/група
VinčaTY - JOUR AU - Todorović, Lidija AU - Stamenković, Gorana AU - Vučetić-Tadić, Biljana AU - Umezawa, Kazuo AU - Božović, Ana M. AU - Yamashita, Shunichi AU - Stanojević, Boban PY - 2021 UR - https://vinar.vin.bg.ac.rs/handle/123456789/9413 AB - The use of targeted inhibitors has shown promise as an effective approach in cancer therapy. However, targeted therapies based only on one drug, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), have limited success, partly because cancer cells engage alternate pathways for survival and proliferation. In the present study, we evaluated whether dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor ?B (NF-?B) inhibitor, can enhance the antitumor activities of 17-AAG, a 90 kDa heat shock protein (Hsp90) inhibitor, in the anaplastic thyroid cancer cell line KTC2. We examined the effect of combined drug treatment vs single drug treatment on cell survival. Isobologram analysis was performed to distinguish the additive vs synergistic effects of the drug combination. Western blotting was performed to investigate apoptosis markers: caspase 3, poly(ADP-ribose) polymerase-one (PARP-1), B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 2 (cIAP-2). Compared to monotherapy, the combined treatment enhanced growth-inhibitory effects in a synergistic manner and strongly potentiated apoptosis. These results demonstrate the first in vitro evidence that a combination of Hsp90 and NF-?B inhibitors is a more effective modality for inhibiting cell proliferation and survival in anaplastic thyroid carcinoma cells than either agent alone, warranting further investigations. T2 - Archives of Biological Sciences T1 - Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2 VL - 73 IS - 1 SP - 31 EP - 38 DO - 10.2298/ABS201010055T ER -
@article{ author = "Todorović, Lidija and Stamenković, Gorana and Vučetić-Tadić, Biljana and Umezawa, Kazuo and Božović, Ana M. and Yamashita, Shunichi and Stanojević, Boban", year = "2021", abstract = "The use of targeted inhibitors has shown promise as an effective approach in cancer therapy. However, targeted therapies based only on one drug, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG), have limited success, partly because cancer cells engage alternate pathways for survival and proliferation. In the present study, we evaluated whether dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor ?B (NF-?B) inhibitor, can enhance the antitumor activities of 17-AAG, a 90 kDa heat shock protein (Hsp90) inhibitor, in the anaplastic thyroid cancer cell line KTC2. We examined the effect of combined drug treatment vs single drug treatment on cell survival. Isobologram analysis was performed to distinguish the additive vs synergistic effects of the drug combination. Western blotting was performed to investigate apoptosis markers: caspase 3, poly(ADP-ribose) polymerase-one (PARP-1), B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis 2 (cIAP-2). Compared to monotherapy, the combined treatment enhanced growth-inhibitory effects in a synergistic manner and strongly potentiated apoptosis. These results demonstrate the first in vitro evidence that a combination of Hsp90 and NF-?B inhibitors is a more effective modality for inhibiting cell proliferation and survival in anaplastic thyroid carcinoma cells than either agent alone, warranting further investigations.", journal = "Archives of Biological Sciences", title = "Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2", volume = "73", number = "1", pages = "31-38", doi = "10.2298/ABS201010055T" }
Todorović, L., Stamenković, G., Vučetić-Tadić, B., Umezawa, K., Božović, A. M., Yamashita, S.,& Stanojević, B.. (2021). Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2. in Archives of Biological Sciences, 73(1), 31-38. https://doi.org/10.2298/ABS201010055T
Todorović L, Stamenković G, Vučetić-Tadić B, Umezawa K, Božović AM, Yamashita S, Stanojević B. Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2. in Archives of Biological Sciences. 2021;73(1):31-38. doi:10.2298/ABS201010055T .
Todorović, Lidija, Stamenković, Gorana, Vučetić-Tadić, Biljana, Umezawa, Kazuo, Božović, Ana M., Yamashita, Shunichi, Stanojević, Boban, "Synergistic effect of 17-allylamino-17-demethoxygeldanamycin with dehydroxymethylepoxyquinomicin on the human anaplastic thyroid carcinoma cell line KTC2" in Archives of Biological Sciences, 73, no. 1 (2021):31-38, https://doi.org/10.2298/ABS201010055T . .