AC-93253 triggers the downregulation of melanoma progression markers and the inhibition of melanoma cell proliferation.
A major challenge in anti-melanoma therapy is to develop treatments that are effective for advanced melanoma patients. Unfortunately, the currently used regimens are not efficient and have unsatisfactory effects on disease progression, thus increasing the pressure to develop new, profitable drugs and to identify new molecular targets. Here, we show for the first time that AC-93253, a SIRT2 inhibitor, exerts a negative effect on the expression of a set of genes involved in the progression and chemoresistance (e.g., oncogenes, apoptosis-related genes, ABC transporter genes, and cell cycle control genes) of melanoma cells. Furthermore, melanoma cells exposed to AC-93253 and doxorubicin displayed altered biological responses, including apoptosis and proliferation, compared to cells exposed to single treatments. Taken together, we conclude that the usage of AC-93253 in combined therapy could be a promising strategy for melanoma patients.
Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
Iwona
I
Karwaciak
Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
Michal
M
Gorzkiewicz
Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
Katarzyna
K
Ryba
Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
Jaroslaw
J
Dastych
Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland.
Lukasz
L
Pulaski
Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland. Electronic address: mratajewski@cbm.pan.pl.
Marcin
M
Ratajewski
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D005810:Multigene Family / Q000187:drug effects; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors / Q000378:metabolism
C542662:AC 93253; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D014408:Biomarkers, Tumor; D004317:Doxorubicin; C474199:SIRT2 protein, human; D056565:Sirtuin 2
ABC transporters; AC-93253; Melanoma; Resistance; SIRT