Table 1.
PPIs in cancer
| Study | PPI effect |
|---|---|
| Mattsson et al120 | In 1991, omeprazole was found to exhibit specific inhibitory activity on the H+/K(+)-ATPase |
| Mizunashi et al121 | In 1993, this research group established that omeprazole decreased bone reabsorption through inhibition of V-ATPase at lysosomal level in osteoclasts in a human clinical setting |
| Luciani et al122 | PPI pretreatment (omeprazole or esomeprazole or pantoprazole) sensitized tumor cell lines (melanoma, adenocarcinoma, and lymphoma) to cisplatin, 5FU, and vinblastine. PPI pretreatment inhibited V-ATPase activity and increased pHe and the pH of lysosomes. Oral pretreatment with omeprazole induced sensitivity of human solid tumors to cisplatin |
| De Milito et al123 | PPIs affected viability of human B cells and increased sensibility to vinblastine. They also induced lysosomal permeabilization which was probably related to apoptosis, which induced cytosolic acidification. PPIs resulted in cytotoxicity for leukemic cells in ALL |
| Capodicasa et al124 | Omeprazole induced apoptosis in polymorphonuclear cells |
| Ferrari et al125 | PPIs chemosensitized human osteosarcoma cells to chemotherapy with cisplatin in cell cultures and xenografts |
| Patel et al126 | Pantoprazole increased the cytotoxicity of doxorubicin in solid tumors (cell culture). Pantoprazole increased endosomal pH |
| Avnet et al127 | The targeting of V-ATPase with siRNA and omeprazole in Ewing sarcoma produced a reduction in cell viability |
| Chen et al128 | Pantoprazole decreased multidrug resistance in gastric adenocarcinoma and decreased cell viability. Pantoprazole decreased pHi and reversed pHi–pHe gradient. Experiments were carried out on cell cultures and xenografts. Also, downregulation of the V-ATPases-mTOR-HIF-1 signaling was found |
| Shen et al129 | Pantoprazole inhibited tumor growth and decreased HIF-1 expression in human gastric adenocarcinoma |
| Patlolla et al130 | Rats fed with omeprazole showed decreases in aberrant crypt formation in a murine model of azoxymethane-induced crypt formation. Omeprazole also increased p21 expression in colon cancer cell lines and decreased antiapoptotic proteins expression |
| Perut et al131 | Sarcomas show increased numbers of acidic lysosomes. Esomeprazole induced dose-dependent cytotoxicity by interfering with proton compartmentalization |
| Azzarito et al132 | Lansoprazole increased sensitization of human melanoma cells to low doses of paclitaxel. This was confirmed in a xenograft model |
| Huang et al133 | Pantoprazole induces apoptosis in gastric cancer cells probably through inhibition of STAT3 |
| Goh et al134 | Esomeprazole increased the antitumor effect of doxorubicin on triple-negative breast cancer cell MDA-MB-468 and showed growth-suppressive activity when used alone |
| Zhang et al135 | Human breast cancer cells treated with lansoprazole showed apoptosis in a dose-dependent way. In xenografts, lansoprazole produced alkalization of lysosomes and increase in ROS |
| Jin et al136 | Omeprazole showed ligand capacity to aryl hydrocarbon receptor, decreasing cell invasion and metastasis in ER-negative breast cancer |
| Salerno et al137 | Rhabdomyosarcoma stem cells showed a very high level of V-ATPase and lysosomal acidity with high invasiveness and reduced cytotoxicity with doxorubicin. Omeprazole increased doxorubicin cytotoxicity, and decreased growth and invasion even at low concentrations of omeprazole |
| Yeo et al29 | Pantoprazole in vivo and in vitro induced apoptosis in gastric cancer cells |
| Udelnow et al138 | Omeprazole inhibited proliferation of pancreatic cancer cells and modulated autophagy |
| Marino et al139 | Esomeprazole induced apoptosis in melanoma cells but also induced autophagic defenses. The administration of an autophagia inhibitor increased malignant cell death due to esomeprazole |
| Vishvakarma and Singh140 | Pantoprazole in a murine model of T cell lymphoma produced an increase in tumoricidal activity of TAMs |
| Yeo et al141 | PPIs induced apoptosis in gastric cancer cells |
Abbreviations: PPIs, proton pump inhibitors; 5FU, 5-fluorouracil; ALL, acute lymphoid leukemia; siRNA, small interfering RNA; ROS, reactive oxygen species; TAMS, tumor associated macrophages.