The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells
Chemotherapy is a powerful anti-tumor therapeutic strategy; however, resistance to treatment remains a serious concern. To overcome chemoresistance, combination therapy with anticancer drugs is a potential strategy. We developed a novel herbal extract, JI017, with lower toxicity and lesser side effe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/12/1881 |
| _version_ | 1827674366212571136 |
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| author | Tae Woo Kim Seong-Gyu Ko |
| author_facet | Tae Woo Kim Seong-Gyu Ko |
| author_sort | Tae Woo Kim |
| collection | DOAJ |
| description | Chemotherapy is a powerful anti-tumor therapeutic strategy; however, resistance to treatment remains a serious concern. To overcome chemoresistance, combination therapy with anticancer drugs is a potential strategy. We developed a novel herbal extract, JI017, with lower toxicity and lesser side effects. JI017 induced programmed cell death and excessive unfolded protein response through the release of intracellular reactive oxygen species (ROS) and calcium in breast cancer cells. JI017 treatment increased the expression of endoplasmic reticulum (ER) stress markers, including p-PERK, p-eIF2α, ATF4, and CHOP, via the activation of both exosomal GRP78 and cell lysate GRP78. The ROS inhibitors diphenyleneiodonium and N-acetyl cysteine suppressed apoptosis and excessive ER stress by inhibiting Nox4 in JI017-treated breast cancer cells. Furthermore, in paclitaxel-resistant breast cancer cell lines, MCF-7R and MDA-MB-231R, a combination of JI017 and paclitaxel overcame paclitaxel resistance by blocking epithelial-mesenchymal transition (EMT) processes, such as the downregulation of E-cadherin expression and the upregulation of HIF-1α, vimentin, Snail, and Slug expression. These findings suggested that JI017 exerts a powerful anti-cancer effect in breast cancer and a combination therapy of JI017 and paclitaxel may be a potential cancer therapy for paclitaxel resistant breast cancer. |
| first_indexed | 2024-03-10T04:38:22Z |
| format | Article |
| id | doaj.art-356f2157333f4d38bcbf512bb6bc7008 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T04:38:22Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-356f2157333f4d38bcbf512bb6bc70082023-11-23T03:32:22ZengMDPI AGAntioxidants2076-39212021-11-011012188110.3390/antiox10121881The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer CellsTae Woo Kim0Seong-Gyu Ko1Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul 130-701, KoreaDepartment of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul 130-701, KoreaChemotherapy is a powerful anti-tumor therapeutic strategy; however, resistance to treatment remains a serious concern. To overcome chemoresistance, combination therapy with anticancer drugs is a potential strategy. We developed a novel herbal extract, JI017, with lower toxicity and lesser side effects. JI017 induced programmed cell death and excessive unfolded protein response through the release of intracellular reactive oxygen species (ROS) and calcium in breast cancer cells. JI017 treatment increased the expression of endoplasmic reticulum (ER) stress markers, including p-PERK, p-eIF2α, ATF4, and CHOP, via the activation of both exosomal GRP78 and cell lysate GRP78. The ROS inhibitors diphenyleneiodonium and N-acetyl cysteine suppressed apoptosis and excessive ER stress by inhibiting Nox4 in JI017-treated breast cancer cells. Furthermore, in paclitaxel-resistant breast cancer cell lines, MCF-7R and MDA-MB-231R, a combination of JI017 and paclitaxel overcame paclitaxel resistance by blocking epithelial-mesenchymal transition (EMT) processes, such as the downregulation of E-cadherin expression and the upregulation of HIF-1α, vimentin, Snail, and Slug expression. These findings suggested that JI017 exerts a powerful anti-cancer effect in breast cancer and a combination therapy of JI017 and paclitaxel may be a potential cancer therapy for paclitaxel resistant breast cancer.https://www.mdpi.com/2076-3921/10/12/1881JI017ER stressROSNox4exosome |
| spellingShingle | Tae Woo Kim Seong-Gyu Ko The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells Antioxidants JI017 ER stress ROS Nox4 exosome |
| title | The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells |
| title_full | The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells |
| title_fullStr | The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells |
| title_full_unstemmed | The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells |
| title_short | The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells |
| title_sort | herbal formula ji017 induces er stress via nox4 in breast cancer cells |
| topic | JI017 ER stress ROS Nox4 exosome |
| url | https://www.mdpi.com/2076-3921/10/12/1881 |
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