Upon treating resistant cells with the calculated IC50 dose of melatonin (13.4 mM), melatonin will directly pass the membrane in a way that is independent of melatonin receptors (our data detected insignificant expression of melatonin receptor genes with melatonin administration for 24 h) to drive cell differentiation events, reduce cancer cell proliferation, and eliminate invasive properties (Grant et al. 2009), then melatonin will directly/indirectly targeting ABC-transporters; ABCB1, ABCC1, ABCC5, and ABCG2 genes. This evidence concerns the gene ABCC5 and cancer.