Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP Suppression
Gastric cancer has been associated with a high incidence and mortality, accompanied by a poor prognosis. Given the limited therapeutic options to treat gastric cancer, alternative treatments need to be urgently developed. Hyperthermia therapy is a potentially effective and safe treatment option for...
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2023-01-01
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author | Chae Ryeong Ahn Hyo In Kim Jai-Eun Kim In Jin Ha Kwang Seok Ahn Jinbong Park Young Woo Kim Seung Ho Baek |
author_facet | Chae Ryeong Ahn Hyo In Kim Jai-Eun Kim In Jin Ha Kwang Seok Ahn Jinbong Park Young Woo Kim Seung Ho Baek |
author_sort | Chae Ryeong Ahn |
collection | DOAJ |
description | Gastric cancer has been associated with a high incidence and mortality, accompanied by a poor prognosis. Given the limited therapeutic options to treat gastric cancer, alternative treatments need to be urgently developed. Hyperthermia therapy is a potentially effective and safe treatment option for cancer; however, certain limitations need to be addressed. We applied 43 °C hyperthermia to AGS gastric cancer cells combined with Ponciri Fructus Immaturus (PF) to establish their synergistic effects. Co-treatment with PF and hyperthermia synergistically suppressed AGS cell proliferation by inducing extrinsic and intrinsic apoptotic pathways. Additionally, PF and hyperthermia suppressed factors related to metastasis. Cell cycle arrest was determined by flow cytometry, revealing that co-treatment induced arrest at the G2/M phase. As reactive oxygen species (ROS) are critical in hyperthermia therapy, we next examined changes in ROS generation. Co-treatment with PF and hyperthermia increased ROS levels, and apoptotic induction mediated by this combination was partially dependent on ROS generation. Furthermore, heat shock factor 1 and heat shock proteins (HSPs) were notably suppressed following co-treatment with PF and hyperthermia. The HSP-regulating effect was also dependent on ROS generation. Overall, these findings suggest that co-treatment with PF and hyperthermia could afford a promising anticancer therapy for gastric cancer. |
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spelling | doaj.art-a74e63d50c004912b0657ece52f8abf62023-11-16T19:17:45ZengMDPI AGBiomedicines2227-90592023-01-0111240510.3390/biomedicines11020405Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP SuppressionChae Ryeong Ahn0Hyo In Kim1Jai-Eun Kim2In Jin Ha3Kwang Seok Ahn4Jinbong Park5Young Woo Kim6Seung Ho Baek7Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USACollege of Korean Medicine, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Republic of KoreaKorean Medicine Clinical Trial Center (K-CTC), Korean Medicine Hospital, Kyung Hee University, Seoul 02447, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of KoreaCollege of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of KoreaCollege of Korean Medicine, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Republic of KoreaCollege of Korean Medicine, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Republic of KoreaGastric cancer has been associated with a high incidence and mortality, accompanied by a poor prognosis. Given the limited therapeutic options to treat gastric cancer, alternative treatments need to be urgently developed. Hyperthermia therapy is a potentially effective and safe treatment option for cancer; however, certain limitations need to be addressed. We applied 43 °C hyperthermia to AGS gastric cancer cells combined with Ponciri Fructus Immaturus (PF) to establish their synergistic effects. Co-treatment with PF and hyperthermia synergistically suppressed AGS cell proliferation by inducing extrinsic and intrinsic apoptotic pathways. Additionally, PF and hyperthermia suppressed factors related to metastasis. Cell cycle arrest was determined by flow cytometry, revealing that co-treatment induced arrest at the G2/M phase. As reactive oxygen species (ROS) are critical in hyperthermia therapy, we next examined changes in ROS generation. Co-treatment with PF and hyperthermia increased ROS levels, and apoptotic induction mediated by this combination was partially dependent on ROS generation. Furthermore, heat shock factor 1 and heat shock proteins (HSPs) were notably suppressed following co-treatment with PF and hyperthermia. The HSP-regulating effect was also dependent on ROS generation. Overall, these findings suggest that co-treatment with PF and hyperthermia could afford a promising anticancer therapy for gastric cancer.https://www.mdpi.com/2227-9059/11/2/405hyperthermiagastric cancerPonciri Fructus Immaturusheat shock proteinsreactive oxygen speciescombination therapy |
spellingShingle | Chae Ryeong Ahn Hyo In Kim Jai-Eun Kim In Jin Ha Kwang Seok Ahn Jinbong Park Young Woo Kim Seung Ho Baek Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP Suppression Biomedicines hyperthermia gastric cancer Ponciri Fructus Immaturus heat shock proteins reactive oxygen species combination therapy |
title | Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP Suppression |
title_full | Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP Suppression |
title_fullStr | Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP Suppression |
title_full_unstemmed | Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP Suppression |
title_short | Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP Suppression |
title_sort | ponciri fructus immatarus sensitizes the apoptotic effect of hyperthermia treatment in ags gastric cancer cells through ros dependent hsp suppression |
topic | hyperthermia gastric cancer Ponciri Fructus Immaturus heat shock proteins reactive oxygen species combination therapy |
url | https://www.mdpi.com/2227-9059/11/2/405 |
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