Triclosan induces ROS‑dependent cell death and autophagy in A375 melanoma cells

Abstract

Melanoma is a common type of cutaneous tumor, but current drug treatments do not satisfy clinical practice requirements. At present, mitochondrial uncoupling is an effective antitumor treatment. Triclosan, a common antimicrobial, also acts as a mitochondrial uncoupler. The aims of the present study were to investigate the effects of triclosan on melanoma cells and the underlying mechanisms. Mitochondrial membrane potential (MMP), mitochondrial morphology, mitochondrial reactive oxygen species (mito-ROS), intracellular superoxide anion and [Ca 2+ ] i were measured using confocal microscopy. It was found that triclosan application was associated with decreased A375 cell viability in a dose-and time-dependent manner and these effects may have cell specificity. Furthermore, triclosan induced MMP depolarization, ATP content decrease, mito-ROS and [Ca 2+ ] i level increases, excessive mitochondrial fission, AMP-activated protein kinase (AMPK) activation and STAT3 inhibition. Moreover, these aforementioned effects were reversed by acetylcysteine treatment. Triclosan acute treatment also induced mitochondrial swelling, which was reversed after AMPK-knockdown associated with [Ca 2+ ] i overload. Cell death was caused by STAT3 inhibition but not AMPK activation. Moreover, triclosan induced autophagy via the ROS/AMPK/p62/microtubule-associated protein 1A/1B-light chain 3 (LC3) signaling pathway, which may serve a role in feedback protection. Collectively, the present results suggested that triclosan increased mito-ROS production in melanoma cells, following induced cell death via the STAT3/Bcl-2 pathway and autophagy via the AMPK/p62/LC3 pathway.

Hyperforin Elicits Cytostatic/Cytotoxic Activity in Human Melanoma Cell Lines, Inhibiting Pro-Survival NF-κB, STAT3, AP1 Transcription Factors and the Expression of Functional Proteins Involved in Mitochondrial and Cytosolic Metabolism

“…In agreement with the increased pAMPK level, acetylCoA carboxylase enzyme (ACC), which is a known target of AMPK activity, has been found phosphorylated as well (pACC, Figure 4 ). AMPK is an activator of mitophagy/autophagy in tumor cells, including melanoma [ 52 ]. Therefore, the expression level of microtubule-associated proteins 1A/1B light chain 3B (LC3B), a known marker of autophagy, was investigated by immunoblotting.…”

Pressure-Spun Fibrous Surgical Sutures for Localized Antibacterial Delivery: Development, Characterization, and In Vitro Evaluation

“…This finding aligns with previous studies in the literature, which have shown that the incorporation of antibacterial agents, such as Tri, can have an impact on cell viability. 55 – 57 The cytotoxicity of Tri has been reported with respect to various cell types, and its effects can be dose-dependent. 58 It is worth noting that in this study the cell viability remains at 70% and above, up to the 20 TPP sample.…”

Oxidative Stress and Autophagy as Key Targets in Melanoma Cell Fate

“…Accordingly, in A375 and BLM cell lines, both autophagy and apoptosis were induced by the proteasome inhibitor bortezomib through the involvement, at least in part, of the ROS-mitochondrial dysregulation-associated pathways [ 91 ]. Mitochondrial dysfunction was also induced by treatment with the antimicrobial triclosan in A375 cells [ 92 ]. Triclosan caused cytotoxicity and cell death acting on ROS signalling and promoting autophagy.…”