Lysosomal and prostasomal hydrolytic enzymes and redox processes and initiation of prostate cancer.
Lysosomes, lysosomal enzymes and oxidant processes are known to be involved in cancer processes. The prostasomes contain proteins and enzymes that would constitute pathways for the hydrolysis of proteins and peptides. However, integrated biochemical and cell biology studies are necessary to understand how lysosomal enzymes and prostasomal enzymes combined with oxidant processes could initiate cancer. Most prostate cancer is likely to be initiated in the prostate duct system. The lysosomal enzymes acid phosphatase and glucosidase and prostasomal proteins and enzymes are found in human semen and therefore have come through prostate ducts. The hypothesis presented here is that the lysosomal enzymes and prostasomes are exocytosed from prostate cells into the duct system of the prostate where their hydrolytic enzymes and oxidative processes, for example, the iron from the iron-sulfur clusters of the prostasomal dehydrogenases, damage proteins and other components of cells leading to the initiation of cancer. Risk factors for prostate cancer are known to initiate activity of lysosomal enzymes and could initiate activity of prostasomal enzymes. These risk factors include: ionizing radiation, oxidative stress, environmental toxicants and dietary components including those with high fat content. Other dietary components in fruits and vegetables protect against prostate cancer and can be hypothesized as decreasing cellular output of lysosomal or protasomal enzymes or inhibiting lysosomal and prostasomal enzymes in the duct system. Measurements of multiple lysosomal and prostasomal enzyme activities and their biochemical pathways are vital to the understanding of protectors to inhibit lysosomal or prostasomal enzyme activities that might be leading to prostate cancer. Inhibitors of lysosomal and prostasomal enzymes can be investigated in cellular and biochemical systems, and these inhibitors could be used to control these enzyme activities in vivo. In situ enzyme analyses including substrates producing fluorescent products are applicable. Screening assays could be developed to detect in vivo lysosomal and prostasomal enzyme activities in semen. Lysosomal enzyme activities may be precursors to the onset of other kinds of cancer with other similar non-invasive screening techniques possible. Present knowledge encompasses mobilization of sperm when prostasomes bind to sperm in semen. A further hypothesis of this study projects that prostasomal dehydrogenases and their NADH products initiate the formation of ATP in the sperm mitochondria which activates flagellar movement. This overall hypothesis suggests protection against prostate cancer by inhibitors of lipid peroxidation including the dietary antioxidants selenium, vitamin E and lycopene and also cysteine glutathione.
Tappel
Al
A
Department of Food Science and Technology, University of California, Davis, CA 95616, USA. altappel@ucdavis.edu
D000230:Adenocarcinoma / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003043:Cocarcinogenesis; D004032:Diet; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005089:Exocytosis; D006801:Humans; D006868:Hydrolysis; D015227:Lipid Peroxidation; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D008954:Models, Biological; D015388:Organelles / Q000201:enzymology; D010084:Oxidation-Reduction; D011467:Prostate / Q000648:ultrastructure; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000378:metabolism; D012307:Risk Factors
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D004791:Enzyme Inhibitors