Resveratrol–zinc combination for prostate cancer management

Figures & data

Table 1. Details about Zn transporter solute carrier family 39 (SLC39)

Gene	Protein	Known information	Status in PCa	References
SLC39A1	ZIP1	The encoded protein is localized to the cell membrane and important for the extraction of Zn from circulation as the primary source of cellular Zn.	Downregulated	13, 37
SLC39A2	ZIP2	ZIP2 and ZIP3 transporter proteins are localized predominantly at the apical cell membrane and important for retention of the Zn in the cellular compartment.	Downregulated	14
SLC39A3	ZIP3		Downregulated	14
SLC39A4	ZIP4	ZIP4 is expressed along the gastrointestinal tract and acts as a major processor of dietary Zn for loading into enterocytes from the apical membrane. ZIP4 has been shown confer resistance to Zn-deficiency induced apoptosis in pancreatic cancer.^38	Downregulated	15, 38, 39
SLC39A5	ZIP5	ZIP5 localizes specifically to the basolateral membrane of polarized cells and carry out serosal-to-mucosal Zn transport.	Not known	40
SLC39A6	ZIP6	ZIP6 overexpression has been noticed in breast cancer which plays a tumor-constraining role.	Not known	41
SLC39A7	ZIP7	ZIP7 transports Zn from the Golgi and endoplasmic reticulum to the cytoplasm.	Not known	42, 43
SLC39A8	ZIP8	ZIP8 is glycosylated and found in the plasma membrane and mitochondria, and functions in the cellular import of Zn at the onset of inflammation. In addition, it can also transport iron, manganese and cadmium.	Not known	44, 45
SLC39A9	ZIP9	ZIP9 regulates cytosolic Zn level, thereby enhances Akt and Erk phosphorrylation in B-cell receptor signaling pathway.	Not known	46
SLC39A10	ZIP10	ZIP10 higher expression has been noticed in breast cancer clinical samples.	Not known	47
SLC39A11	ZIP11	ZIP11 is a Zn importer, and its expression is regulated by Zn via metal-responsive transcription factor-1 (hMTF-1) binding to metal response element sequences (MREs) of the ZIP11 promoter.	Not known	48
SLC39A12	ZIP12	ZIP12 highly expresses in the human brain where it is required for neurulation and neurite extension.	Not known	49
SLC39A13	ZIP13	ZIP13 plays an important role in Zn homeostasis by controlling vesicular Zn storage.	Not known	50
SLC39A14	ZIP14	Like ZIP8, ZIP14 is also broad scope metal transporter which mediate the cellular uptake of nutritionally important metals as well as the toxic heavy metal cadmium. ZIP14 downregulation has been noticed in Hepatocellular cancer.	Not known	45, 51

Table 2. Details about Zn transporter solute carrier family 30 (SLC30)

Gene	Protein	Known information	Status in PCa	References
SLC30A1	ZnT1	ZnT1 play a key role in the regulation of free Zn levels and thereby confers cellular resistance from Zn toxicity.	Lower levels of ZnT1 has been noticed in human PCa compare with hyperplastic tissues	52, 53
SLC30A2	ZnT2	Both Zn concentrations and ZnT2 expression in the prostate dorsolateral lobes are substantially higher than in the ventral lobes.	ZnT2 is reported to be correlative to Zn level in the dorsolateral lobe.	54
SLC30A3	ZnT3	ZnT3 has been associated with Alzheimer disease, airway diseases and diabetes.	ZnT3 presence has been reported in various cells including PCa, and is regulated by age, hormones, fatty acids, etc.	55
SLC30A4	ZnT4	Like other ZnTs, ZnT4 also transports Zn out of the cytoplasm.	Decreased level of ZnT4 has been shown in benign prostatic hyperplasia and PCa.	56
SLC30A5	ZnT5	ZnT5 play a key role in the absorption of dietary Zn. Methylation of ZnT5 promoter region contributes to reduction in ZnT5 expression and thereby age-related decline in Zn status.	Not known	57
SLC30A6	ZnT6	ZnT6 function in transporting the cytoplasmic Zn into the Golgi apparatus as well as the vesicular compartment.	Not known	58
SLC30A7	ZnT7	ZnT7 localizes on the Golgi membrane and mainly expresses in the intestinal tract, lung, and prostate.	A null-mutation of the ZnT7 accelerates formation of prostate tumor in TRAMP mice.	59
SLC30A8	ZnT8	ZnT8 is highly expressed in the pancreas, particularly in islets of Langerhans, and involved in the accumulation of Zn in intracellular vesicles.	Not known	60
SLC30A9	ZnT9	ZnT9 is shown to be expressed at low levels in leukocytes.	Not known	61
SLC30A10	ZnT10	ZnT10 functions in efflux direction and shows differential expression pattern in human tissue with highest levels in small intestine, liver and brain.	Not known	62

Figure 1. A schematic representation showing plausible scenario of resveratrol-Zn combinatorial action for PCa management.

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