The Anticancer Potential of Doxycycline and Minocycline—A Comparative Study on Amelanotic Melanoma Cell Lines

Abstract

Malignant melanoma is still a serious medical problem. Relatively high mortality, a still-growing number of newly diagnosed cases, and insufficiently effective methods of therapy necessitate melanoma research. Tetracyclines are compounds with pleiotropic pharmacological properties. Previously published studies on melanotic melanoma cells ascertained that minocycline and doxycycline exerted an anti-melanoma effect. The purpose of the study was to assess the anti-melanoma potential and mechanisms of action of minocycline and doxycycline using A375 and C32 human amelanotic melanoma cell lines. The obtained results indicate that the tested drugs inhibited proliferation, decreased cell viability, and induced apoptosis in amelanotic melanoma cells. The treatment caused changes in the cell cycle profile and decreased the intracellular level of reduced thiols and mitochondrial membrane potential. The exposure of A375 and C32 cells to minocycline and doxycycline triggered the release of cytochrome c and activated initiator and effector caspases. The anti-melanoma effect of analyzed drugs appeared to be related to the up-regulation of ERK1/2 and MITF. Moreover, it was noticed that minocycline and doxycycline increased the level of LC3A/B, an autophagy marker, in A375 cells. In summary, the study showed the pleiotropic anti-cancer action of minocycline and doxycycline against amelanotic melanoma cells. Considering all results, it could be concluded that doxycycline was a more potent drug than minocycline.

Gene signature reveals decreased SOX10-dependent transcripts in malignant cells from immune checkpoint inhibitor-resistant cutaneous melanomas

“…Others have shown that A375 cell lines have low MITF mRNA levels at baseline. 31 , 50 Our results also identified genes not previously observed as predicted targets of SOX10 in melanoma, including Sphingosine-1-Phosphate Receptor 2 (S1PR2) and Adhesion G Protein-Coupled Receptor G6 (ADGRG6). Stimulation of S1PR2 inhibits Rac and activates RhoA in B16F10 mouse melanoma cells, reducing migration and invasion.…”

The Assessment of Anti-Melanoma Potential of Tigecycline—Cellular and Molecular Studies of Cell Proliferation, Apoptosis and Autophagy on Amelanotic and Melanotic Melanoma Cells

“…Comparing the calculated EC 50 values for tigecycline with those obtained for doxycycline [ 11 , 33 ] and minocycline [ 12 , 33 ], it can be concluded that the drugs exhibit a similar effect against melanotic melanoma. The values for 72-h incubation of the drugs with COLO 829 cells were as follows: 16.3 µM for doxycycline, 13.9 µM for minocycline, and 19.2 µM for tigecycline.…”

“…This creates a unique opportunity to use tetracyclines in the treatment of skin diseases, including melanoma. Previous studies showed the anti-melanoma potential of doxycycline, minocycline, and chlortetracycline [ 11 , 12 , 33 , 34 ]. The obtained results allowed for the conclusion that the activity of tetracyclines against melanoma cells is associated with the inhibition of cell proliferation and the induction of apoptosis.…”

Eravacycline, an antibacterial drug, repurposed for pancreatic cancer therapy: insights from a molecular-based deep learning model

“…Eravacycline was ranked 17th out of the 1371 ranked molecules. We gave the drug higher priority due to the known anti-cancer activity of tetracyclines [ 25 ] and its commercial availability.…”