Diallyl disulfide effect on the invasion and migration ability of HL-60 cells with a high expression of DJ-1 in the nucleus through the suppression of the Src signaling pathway

Abstract

The present study examined the effect of diallyl disulfide (DADS) on the invasion and migration ability of HL-60 cells with a high expression of parkinsonism associated deglycase (DJ-1) in the nucleus (HHDN), and its molecular mechanism. A western blot assay was used to measure the effects of DADS and an Src inhibitor on the expression of DJ-1 and the Src signal pathway in HHDN. The effects of DADS and Src inhibitors on the invasion and migration ability of HHDN was detected using Transwell migration and invasion chamber experiments. The experiments were divided into three groups: A control group (HL-60 cells), an empty vector group and a high expression group (HHDN cells). Western blot assays revealed that the expression of DJ-1 in HHDN was inhibited in a time-dependent manner following treatment with DADS for 24, 48 and 72 h. Following DADS treatment, the expression of phosphorylated Src (p-Src) and phosphorylated Fak (p-Fak) were significantly decreased in all groups compared with the untreated groups, however the expression level of Src, Fak and integrin did not change significantly. Western blot analysis results revealed that following treatment with DADS and Src inhibitor, the expression levels of p-Src and p-Fak significantly decreased in all three groups compared with untreated groups, whereas the expression levels of Src, Fak and integrin did not change significantly. The expression of DJ-1 in HHND was inhibited in time-dependent manner following treatment with DADS and Src inhibitor for 24, 48 and 72 h. Transwell migration and invasion assay results revealed that DADS and Src inhibitors may suppress migration and invasion in leukemic cells, and a combination of the two treatments may result in more efficient suppression. DADS may downregulate DJ-1-mediated invasion and migration in leukemic cells through suppressing the Src-Fak-Integrin signaling pathway, and the Src inhibitor may enhance the antitumor effect of DADS.

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

“…The anticancer potency of DADS has been explored in vitro and in vivo studies. 4,20,23 The MTT results showed that DADS apparently inhibited growth and survival of U2OS and MG-63 cells in a concentrationas well as time-dependent manner. Cell colony formation and transwell assays further revealed that DADS treatment showed antiproliferation and anti-invasion properties in OS cells.…”

“…This emphasizes the need for the development for safer, natural, and nontoxic compounds as chemotherapeutic agents. The anticancer potency of DADS has been explored in vitro and in vivo studies . The MTT results showed that DADS apparently inhibited growth and survival of U2OS and MG‐63 cells in a concentration‐ as well as time‐dependent manner.…”

Novel Insights into PARK7 (DJ-1), a Potential Anti-Cancer Therapeutic Target, and Implications for Cancer Progression

“…Diallyl disulfide (DADS) has anti-cancer potential, and treatment with DADS induces apoptosis and inhibits the metastatic potential of leukemia cells by suppressing the expression of oncoproteins, including PARK7 [128]. DADS inhibits the activation of Src and focal adhesion kinase (FAK) by reducing the expression of PARK7 [129].…”

Redox-sensitive DJ-1 protein: an insight into physiological roles, secretion, and therapeutic target

“…The synthetic antifungal agent Ciclopirox olamine has been reported to downregulate DJ-1 expression leading to mitochondrial dysfunction and ROS accumulation, thereby inhibiting colorectal cancer growth (Zhou et al, 2019). Furthermore, diallyl disulfide reduced DJ-1 expression that suppresses the Src pathway, leading to induction of apoptosis and inhibition of metastasis potential of leukemia cells (Liu et al, 2018). In addition, the DJ-1 suppression efficacy of paclitaxel leads to the inhibition of breast cancer metastasis (Ismail et al, 2018) and the transformation of NIH3T3 cells (MacKeigan et al, 2003) has been evaluated.…”