A novel mechanism of cannabidiol in suppressing ovarian cancer through LAIR‐1 mediated mitochondrial dysfunction and apoptosis

Abstract

Cannabidiol (CBD) is a nonpsychoactive cannabinoid compound. It has been shown that CBD can inhibit the proliferation of ovarian cancer cells, but the underlying specific mechanism is unclear. We previously presented the first evidence for the expression of leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), a member of the immunosuppressive receptor family, in ovarian cancer cells. In the present study, we investigated the mechanism by which CBD inhibits the growth of SKOV3 and CAOV3 ovarian cancer cells, and we sought to understand the concurrent role of LAIR-1. In addition to inducing ovarian cancer cell cycle arrest and promoting cell apoptosis, CBD treatment significantly affected the expression of LAIR-1 and inhibited the PI3K/AKT/mTOR signaling axis and mitochondrial respiration in ovarian cancer cells. These changes were accompanied by an increase in ROS, loss of mitochondrial membrane potential, and suppression of mitochondrial respiration and aerobic glycolysis, thereby inducing abnormal or disturbed metabolism and reducing ATP production. A combined treatment with N-acetyl-L-cysteine and CBD indicated that a reduction in ROS production would restore PI3K/AKT/mTOR pathway signaling and ovarian cancer cell proliferation. We subsequently confirmed that the inhibitory effect of CBD on the PI3K/AKT/mTOR signal axis and mitochondrial bioenergy metabolism was attenuated by knockdown of LAIR-1. Our animal studies further support the in vivo anti-tumor activity of CBD and suggest its mechanism of action. In summary, Li Ma and Huachang Zhang contributed equally to this study.

Perfluorooctane sulfonate‐induced apoptosis in kidney cells by triggering the NOX4/ROS/JNK axis and antagonism of cannabidiol

“…CBD is highly appreciated as a product with many beneficial pharmacological effects, including antioxidant and anti-tumor properties. 33,37,43 And CBD has been shown to be a protective effect in several kidney injuries. 44,45 To investigate the potential mechanisms of renal injury caused by PFOS exposure and the protective effects of CBD, we developed an in vivo and in vitro PFOS exposure model and a CBD treatment model.…”

“…Therefore, it is important to explore the mechanisms of PFOS nephrotoxicity and seek medical candidates or antagonists. CBD is highly appreciated as a product with many beneficial pharmacological effects, including antioxidant and anti‐tumor properties 33,37,43 . And CBD has been shown to be a protective effect in several kidney injuries 44,45 .…”

REG3A promotes proliferation and DDP resistance of ovarian cancer cells by activating the PI3K/Akt signaling pathway

“…OC poses a serious threat to the lives of patients. [18][19][20][21][22] Currently, the most common way to treat OC is surgical resection and adjuvant chemotherapy. 23 However, the prognosis of OC patients remains unsatisfactory.…”

“…OC poses a serious threat to the lives of patients 18–22 . Currently, the most common way to treat OC is surgical resection and adjuvant chemotherapy 23 .…”

Integrated transcriptome and cell phenotype analysis suggest involvement of PARP1 cleavage, Hippo/Wnt, TGF-β and MAPK signaling pathways in ovarian cancer cells response to cannabis and PARP1 inhibitor treatment

“…Treatment with Laetrile and ‘CBD oil’ that contains multiple molecules altered expression of genes in low-grade serous ovarian cancer in a single patient case-study ( Barrie et al, 2019 ). In addition, it was shown in vitro and in vivo that CBD inhibits OC cell growth ( Ma et al, 2023 ). Based on cell line studies it was suggested that it inhibits cell growth by disrupting the LAIR-1-mediated interference with PI3K/AKT/mTOR pathway and mitochondrial bioenergy metabolism ( Ma et al, 2023 ).…”