Diallyl Sulfide Promotes Cell-Cycle Arrest Through the p53 Expression and Triggers Induction of Apoptosis Via Caspase- and Mitochondria-Dependent Signaling Pathways in Human Cervical Cancer Ca Ski Cells

Abstract

Diallyl sulfide (DAS) is a component of garlic (Alliaceae family). Although diallyl polysulfide has been shown to exhibit anticancer activities, no report explored DAS-affected cell death in human cervical cancer cells in vitro. This study investigated DAS affected on cell-cycle regulation and apoptosis in human cervical cancer Ca Ski cells. DAS at 25-100 μM decreased the viability of Ca Ski cells by increasing G0/G1 phase arrest followed by induction of apoptosis in concentration- and time-dependent effects. Flow cytomteric assay indicated that DAS (75 μM) promoted the production of Ca(2+) accumulation and decreased the level of mitochondrial membrane potential in Ca Ski cells. Western blotting showed that 75 μM of DAS-induced G0/G1 phase arrest was mediated through the increased expression of p21, p27, and p53 with a simultaneous decrease in CDK2, CDK6, and CHK2 expression. The characteristics of apoptosis, such as morphological changes and DNA condensation, altered the ratio of Bax/Bcl-2 and sub-G1 phase occurred in Ca Ski cells after exposure to DAS. Furthermore, DAS induced mitochondrial dysfunction, leading to the release of cytochrome c for causing apoptosis in Ca Ski cells. These findings suggest that DAS might be a potential chemotherapeutic agent for the treatment of cervical cancer.

RETRACTED: FV‐429 Induced Apoptosis Through ROS‐Mediated ERK2 Nuclear Translocation and p53 Activation in Gastric Cancer Cells

“…ERK2 was translocated into the nucleus under the regulation of ROS, therefore we infer ERK2 probably entered the nucleus to phosphorylate and activate one or more transcription factors. As a vital tumor suppressor, p53 exerted its antitumor effects mainly by transactivation of diverse target genes including Bax, Apaf‐1 and caspase‐6, or to induce apoptosis independent of its transactivation ability [Wallace and Cotter, ; Chiu et al, ; Ngok‐Ngam et al, ]. Collectively, these results indicated that by virtue of nuclear translocation, ERK2 phosphorylated and activated p53 in the nucleus.…”

Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1

“…[22] reported DAS-mediated cell cycle arrest and induction of apoptosis in Ca Ski cervical cancer cells. Decreased viability of Ca Ski cells was observed following enhanced expression of cell cycle-regulatory proteins (p21, p27, and p53) and subsequent G 0 /G 1 cell cycle arrest.…”

Diallyl sulfide alleviates cisplatin‐induced nephrotoxicity in rats via suppressing NF‐κB downstream inflammatory proteins and p53/Puma signalling pathway

“…Moreover, DAS has been shown to adopt a multi‐prong strategy to target multiple signalling pathways leading to induction of apoptosis . DAS decreased cell proliferation and induced apoptosis via mitochondrial signalling pathway in ATC cells as well as DAS upregulated expression of p53 . Contrary to these data, DAS provided protection against DMBA‐induced oxidative stress‐mediated apoptosis and offered neuroprotection against transient focal cerebral ischemia via anti‐apoptosis .…”

“…21,22 DAS decreased cell proliferation and induced apoptosis via mitochondrial signalling pathway in ATC cells 23 as well as DAS upregulated expression of p53. 24 Contrary to these data, DAS provided protection against DMBA-induced oxidative stress-mediated apoptosis 25 and offered neuroprotection against transient focal cerebral ischemia via anti-apoptosis. 26 It is worth mentioning that DAS (100 mg/kg) mitigated Cis-induced nephrotoxicity by reducing expression of NF-κB and Cyclooxygenase-2 (Cox-2) in Cis-treated rats.…”