Next Article in Journal
Pardaxin Activates Excessive Mitophagy and Mitochondria-Mediated Apoptosis in Human Ovarian Cancer by Inducing Reactive Oxygen Species
Previous Article in Journal
Impulse Noise Induced Hidden Hearing Loss, Hair Cell Ciliary Changes and Oxidative Stress in Mice
Previous Article in Special Issue
Resveratrol Targets a Variety of Oncogenic and Oncosuppressive Signaling for Ovarian Cancer Prevention and Treatment

The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul 130-701, Korea
Author to whom correspondence should be addressed.
Academic Editors: Simone Carradori and Alessandra Napolitano
Antioxidants 2021, 10(12), 1881; (registering DOI)
Received: 15 October 2021 / Revised: 11 November 2021 / Accepted: 22 November 2021 / Published: 25 November 2021
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. View Full-Text
Keywords: JI017; ER stress; ROS; Nox4; exosome JI017; ER stress; ROS; Nox4; exosome
Show Figures

Figure 1

MDPI and ACS Style

Kim, T.W.; Ko, S.-G. The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells. Antioxidants 2021, 10, 1881.

AMA Style

Kim TW, Ko S-G. The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells. Antioxidants. 2021; 10(12):1881.

Chicago/Turabian Style

Kim, Tae W., and Seong-Gyu Ko. 2021. "The Herbal Formula JI017 Induces ER Stress via Nox4 in Breast Cancer Cells" Antioxidants 10, no. 12: 1881.

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop