Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer

Abstract

Diallyl disulfide (DADS), a volatile component of garlic oil, has various biological properties, including antioxidant, antiangiogenic and anticancer effects. The present study aimed to explore novel targets of DADS that may slow or stop the progression of breast cancer. First, xenograft tumor models were created by subcutaneously injecting MCF-7 and MDA-MB-231 breast cancer cells into nude mice. Subsequently, western blot analysis was performed to investigate the expression of tristetraprolin (TTP), urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in the xenograft tumors, and cell cultures. Tablet cloning, Transwell and wound healing assays revealed that DADS treatment significantly inhibited the proliferation, invasion and migration of breast cancer cells. In addition, DADS treatment led to significant downregulation of uPA and MMP-9 protein expression, but significantly upregulated TTP expression in vivo and in vitro. Knocking down TTP expression using small interfering RNA reversed the aforementioned effects of DADS, which suggests TTP is a key target of DADS in inhibiting the progression of breast cancer.

Diallyl disulfide suppresses FOXM1‐mediated proliferation and invasion in osteosarcoma by upregulating miR‐134

“…DADS has been shown to decrease the formation of carcinogen‐induced cancer and to inhibit the proliferation of various types of cancer cells . The actions of DADS include activation of the metabolizing enzymes that detoxify carcinogens, suppression of the formation of DNA adducts, antioxidant formation, regulation of cell‐cycle arrest, histone modification, induction of apoptosis and cell differentiation, and inhibition of angiogenesis and cell invasion . However, the antitumor effects of DADS against OS remain to be determined.…”

Diallyl disulfide and diallyl trisulfide in garlic as novel therapeutic agents to overcome drug resistance in breast cancer

“…DADS reduces tumor size by inducing apoptosis in the xenograft model, suggesting that DADS may be used as a potential therapeutic agent for treating or preventing BC [ 76 ]. Furthermore, DADS treatment remarkably reduces the proliferation, invasion, and migration of MDA-MB-231 BC cells in a xenograft tumor model and in an in vitro cell line model by downregulating uPA and MMP-9 expression and upregulating tristetraprolin expression [ 77 ]. A protein-nanoemulsion of DADS and α-linolenic acid substantially inhibits the proliferation of BC cells by inducing cell cycle arrest and apoptosis at the Go/G1 phase, via inhibition of the ERK1/2 pathway [ 78 ].…”

“… Garlic compound Cellular mechanism affected Signaling pathway affected by Refs. Allyl sulfur compounds Exert proapoptotic activity Activating p53 [ 74 ] DADS and DATS Exert an anti-proliferative effect on MDR-colorectal carcinoma cells Changing the permeability of mitochondria [ 75 ] DADS Reduce the viability and metastatic potential of TNBC cells Downregulating MMP-9 and promoting the reversal of EMT through inhibition of the β-catenin signaling pathway [ 76 ] DADS Reduce the proliferation, invasion, and migration of MCF-7 and MDA-MB-231 BC cells Downregulating uPA and MMP-9 expression and upregulating TTP expression in vitro and in vivo [ 77 ] DADS Inhibit the proliferation of BC cells Inducing cell cycle arrest and apoptosis at the G0/G1 phase, via inhibition of the ERK1/2 pathway [ 78 ] DADS Cause apoptosis in BC cells Increasing the expressions of BAX, BAD, caspase-3, and caspase-9 [ 79 ] DADS Induce cytotoxicity in BC cells Downregulating BCL2 and survivin and upregulating caspase-9 [ 80 ] DATS Ameliorate ER stress-induced apoptosis and reduce tumor growth of BC Progressive activation of ER stress proteins, such as CHOP/GADD153 and GRP78/Bip, and upregulation of other proteins, such as ATF4 and eIF2 [ 81 ] DADS Decrease FOXM1-dependent invasion of BC cells Enhancing the expression of miR-134 [ 82 ] …”

Tris(methylthio)methane Produced by Mortierella hyalina Affects Sulfur Homeostasis in Arabidopsis

“…Diallyl disulfide (DADS), a volatile from garlic, is perhaps the best studied organosulfide, due to its anticancer ability (Yi and Su, 2013;Xiong et al , 2018;Agassi et al , 2020;Liet al , 2018). It increases GSH levels and regulates antioxidant enzyme activity, leading to reduced oxidative stress in animal models (Demeuleet al , 2004;Hassanein et al , 2021;Wei et al , 2021).…”