To establish the cytotoxic effects of lysosomal inhibitors, we assessed the viability of A375P melanoma, RKO colon carcinoma, and MIA PaCa-2 pancreatic cancer cell lines treated with the vacuolar H+-ATPase inhibitor bafilomycin-A1 (100 nM); PPT1 inhibitors DC661 (3 μM) or HCQ (10 μM or 30 μM); palmitate mimetic hexadecylsulfonyl fluoride (HDSF; 60 μM); cathepsin inhibitors pepstatin A (PepA; 10 μg/mL), E64 (PepA; 10 μg/mL), or PepA+E64; and lysosomal membrane disruptor Leu-Leu methyl ester hydrobromide (20 μM) for 48 hours. This evidence concerns the gene PPT1 and melanoma.