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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Main Authors: Chae Ryeong Ahn, Hyo In Kim, Jai-Eun Kim, In Jin Ha, Kwang Seok Ahn, Jinbong Park, Young Woo Kim, Seung Ho Baek
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/2/405
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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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