期刊
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
卷 69, 期 2, 页码 420-430出版社
WILEY
DOI: 10.1002/bab.2119
关键词
cannabinoids; CBD; ER stress; ROS; UPR
资金
- National Research Foundation (NRF)
- Nelson Mandela University (NMU)
- SAMRC
ER stress is an imbalance between protein-folding load and ER capacity, which can be re-established through UPR. Studies suggest that CBD may induce ER stress via Ca2+ influx through the TRPV1 receptor, increasing ROS levels and disrupting protein folding.
Endoplasmic reticulum (ER) stress is an imbalance between the protein-folding load and capacity of ER. It can be induced by various physiological conditions, activating the unfolded protein response (UPR) to re-establish homeostasis, promoting cell survival. Under severe or chronic stress, apoptosis is induced. Normal cells generally do not experience continuous ER stress induction. The stressful conditions experienced in the tumor microenvironment facilitate chronic ER stress and UPR activation, which plays a pivotal role in tumour survival. Exacerbation of pre-existing ER stress can trigger cancer cell death, with a minimal effect on normal cells. Current literature suggests that cannabinoid treatment may induce cancer cell death via ER stress; however, little is known about the mechanisms of induction. This study proposed that cannabidiol (CBD) mechanism occurred through the influx of Ca2+ via the TRPV1 receptor, and increasing reactive oxygen species (ROS) production affects protein folding and induces ER stress. ER stress was induced, and detection and quantification were completed using Thioflavin T staining and GRP78 by western blot analysis. The effect of cannabinoid treatment on ROS production and Ca2+ influx was measured. CBD was the most potent ER stress inducer, significantly increasing Ca2+ and ROS accumulation. Concomitant treatment with CBD and an antioxidant significantly increased cell viability and decreased ER stress induction in the MCF7 cell line. Concomitant treatment with a TRPV1 antagonist increased viability in this cell line. In conclusion, the data suggested that CBD induced ER stress via Ca2+ influx through the TRPV1 receptor, thereby elevating intracellular ROS levels and disrupting protein folding.
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