ROS-induced autophagy reduces B16F10 melanoma cell proliferative activity

Abstract

Cancer is a pathology characterized by increased cell progression and/or reduced programmed cell death. Melanoma shows a rapid increase in cell progression and its resistance to chemotherapy is associated with uncontrolled apoptosis and to mechanisms that increase the flow of the drug out of the cell. The objective of this study was to evaluate the effects of photodynamic therapy (PDT) on the cell proliferation and cellular alterations in B16F10 murine melanoma. For that, four experimental groups were evaluated: the control group; laser group (ʎ = 660 ηm, 40 mW, 2.4 J/cm); photosensitizer group (solution containing methylene blue and toluidine blue 1:1-12.5 μg/mL); PDT group. The incubation time was 30 min. Fluorescence microscopy assays were performed without fixation with the DAPI, monodansylcadaverine (MDC), and dihydroethidium (DHE) probes. Cell proliferation was also determined at 24-h time. The tests were performed in triplicate and the statistical test used was ANOVA with Tukey post-test. The results demonstrate that the plasma membrane of the cells of all the experimental groups remained intact, ROS production and autophagy significantly increased (p < 0.0005 and p < 0.0071, respectively) only in the PDT group. The cell proliferation essay showed a reduction of 74.2% on the PDT group in relation to the control group. The present study demonstrated that oxidative stress promoted by photodynamic therapy may induce autophagy and consequently reduce cell proliferation in B16F10 melanoma.

ROS as Regulators of Cellular Processes in Melanoma

“…A similar effect is exerted by Nexrutine that increases the constitutively elevated oxidative stress in melanoma cells to inhibit their survival mediated by PI3K/AKT/mTOR [ 169 ]. Photodynamic therapy-induced ROS increase has been shown to significantly reduce melanoma proliferation through cell autophagy mechanism, such supporting the notion that the oxidative stress is responsible of melanoma cell damaging [ 170 ]. Several compounds are able to induce apoptosis in melanoma cells through ROS generation by either mitochondria-dependent [ 171 ] or mitochondria-independent pathways [ 172 ].…”

Plasma-activated medium triggers cell death and the presentation of immune activating danger signals in melanoma and pancreatic cancer cells

“…These data are in agreement with those previously reported, underscoring the fact that the MM cell lines are intrinsically autophagic and that this autophagy is higher in the presence of BRAF mutations, as evident in Hmel1 cells 56 . However, it is known that ROS can kill cells through either apoptosis or autophagy 69–71 , but, it was demonstrated for the first time that PALM might inhibit proliferation through various cell death mechanisms.…”

Impact of ROS Generated by Chemical, Physical, and Plasma Techniques on Cancer Attenuation

“…A vital marker of DSB is the particular phosphorylation of serine 139 on the H 2 AX histone (γ-H 2 AX), which is normally determined immediately after the plasma treatment [251]. Although apoptosis is the main and the most prominent pathway derived by plasma-based treatment, in some cancer cell lines, plasma treatment is reported to follow autophagy; both processes (autophagy and apoptosis) may have occurred simultaneously [252,253,254]. The enhanced oxidative stress has the ability to initiate autophagy.…”