434:
cells. ZnPP works in combination with anticancer drugs to increase cytotoxicity. ZnPP inhibits tumor growth especially solid tumors. Tumors from brain cancer, colon cancer, prostate cancer, renal cell cancer, oral squamous cell cancer, and leukemia all show a susceptibility to ZnPP due to increase expression of heme oxygenase. The inhibition of heme oxygenase leads to an increase of reactive oxidative species in the cell which sensitizes the cells to chemotherapeutic agents. Increased reactive oxidative species can cause apoptosis in cancer cells and reduce drug resistance when exposed to ZnPP due to loss of the heme oxygenase coping mechanism. The combination of these two therapies is highly effective in treating cancer in experiments thus far, and is a possible new method for overcoming drug resistance. The reduced coping ability of tissues treated with ZnPP also increases radiosensitivity. Cells treated with ZnPP and radiation as opposed to simply one of the two are less viable and more likely to stay in G1 phase of the cell cycle, rather than progress to the G2 phase. ZnPP and radiation combination therapy shows more apoptosis than the same amount of radiation displaying that ZnPP puts stress on cancerous tissue. ZnPP have been injected in a number of trials on solid tumors, but can be utilized more broadly when effectively delivered to cancer cells and not healthy cells. A targeted delivery system is needed to fully exploit the uses of ZnPP as a therapeutic agent and heme oxygenase inhibitor due to the potential side effects of free ZnPP on healthy tissue. Reducing the anti-oxidant capability of healthy cells can reduce effects that would have been favorable. However ZnPP have been encapsulated in nanoparticles with specialized coating for drug delivery inside the body. ZnPP did not show any reduce inhibitory potential on heme oxygenase when loaded into nanoparticles. Similarly ZnPP loaded into nanoparticles has a higher cytotoxicity than free ZnPP after two days due to a more favorable release rate as well as better biodistribution and internalization. The possible negative effects on major organs were not seen and blood distribution is more desirable in ZnPP loaded nanoparticles than free ZnPP. The specific inhibition of heme oxygenase using nanoparticles with encapsulated ZnPP reduces side effects and is likely the future method of administering ZnPP treatment.
212:
103:
24:
277:
421:
Porphyrin complexes of zinc have been known since the 1930s. In 1974 ZPP was identified as a major non-heme porphyrin formed in red cells as the result of lead poisoning or iron deficiency., It was already known at this time that non-heme protoporphyrin IX levels were elevated in these conditions,
433:
ZnPP is a competitive inhibitor of heme oxygenase. Heme oxygenase is a cytoprotective enzyme that copes with oxidative stress on a cell and shows higher expression in cancerous tissues. ZnPP suppression of heme oxygenase reduces cell viability of cancer cells and increases cytotoxicity in cancer
609:
Crowell R, Ferris AM, Wood RJ, Joyce P, Slivka H (July 2006). "Comparative effectiveness of zinc protoporphyrin and hemoglobin concentrations in identifying iron deficiency in a group of low-income, preschool-aged children: practical implications of recent illness".
952:
Rouhani H, Sepehri N, Montazeri H, Khoshayand MR, Ghahremani MH, Ostad SN, et al. (August 2014). "Zinc protoporphyrin polymeric nanoparticles: potent heme oxygenase inhibitor for cancer therapy".
422:
but prior investigators had used acidic extraction methods in their assays that converted ZPP to unbound
Protoporphyrin IX. The early literature on quantifying zinc-PP levels may be unreliable.
442:
Zinc porphyrins are always five- or six-coordinate. Because the axial ligands are labile, these complexes are often depicted with planar structures. Planar zinc(II) complexes are unknown.
290:
1112:"Upregulation of heme oxygenase-1 in colorectal cancer patients with increased circulation carbon monoxide levels, potentially affects chemotherapeutic sensitivity"
555:
Verschoor M, Herber R, Zielhuis R, Wibowo A (1987). "Zinc protoporphyrin as an indicator of lead exposure: precision of zinc protoporphyrin measurements".
406:
The fluorescent properties of ZPP in intact red cells allows the ZPP/heme molar ratio to be measured quickly, at low cost, and in a small sample volume.
1166:
Zhang W, Qiao T, Zha L (October 2011). "Inhibition of heme oxygenase-1 enhances the radiosensitivity in human nonsmall cell lung cancer a549 cells".
655:"Is Erythrocyte Protoporphyrin a Better Single Screening Test for Iron Deficiency Compared to Hemoglobin or Mean Cell Volume in Children and Women?"
1219:
1000:"Zinc Protoporphyrin Suppresses β-Catenin Protein Expression in Human Cancer Cells: The Potential Involvement of Lysosome-Mediated Degradation"
796:
Lamola AA, Yamane T (December 1974). "Zinc protoporphyrin in the erythrocytes of patients with lead intoxication and iron deficiency anemia".
1060:
Kang KA, Maeng YH, Zhang R, Yang YR, Piao MJ, Kim KC, et al. (August 2012). "Involvement of heme oxygenase-1 in Korean colon cancer".
390:
297:
169:
1212:
190:
516:"The interpretation of zinc protoporphyrin changes in lead intoxication: a case report and review of the literature"
893:
Kongpetch S, Kukongviriyapan V, Prawan A, Senggunprai L, Kukongviriyapan U, Buranrat B (2012-04-13). Sim RB (ed.).
349:
333:
136:
379:
130:
1433:
895:"Crucial role of heme oxygenase-1 on the sensitivity of cholangiocarcinoma cells to chemotherapeutic agents"
98:
1527:
1205:
1626:
1605:
1533:
467:
1704:
1523:
1513:
1331:
1237:
1011:
906:
805:
564:
374:
1458:
207:
1699:
1519:
1474:
320:. It is a red-purple solid that is soluble in water. The complex and related species are found in
50:
1597:
355:
Zinc protoporphyrin levels can be elevated as the result of a number of conditions, for instance:
1639:
1509:
1085:
977:
829:
635:
588:
369:
1286:
1438:
1366:
1316:
1183:
1143:
1077:
1039:
969:
934:
856:
821:
778:
737:
686:
627:
580:
537:
493:
317:
1662:
1652:
1561:
1555:
1505:
1298:
1175:
1133:
1123:
1069:
1029:
1019:
961:
924:
914:
813:
768:
727:
717:
676:
666:
619:
572:
527:
483:
229:
178:
60:
1618:
1376:
1321:
1261:
364:
1015:
910:
809:
568:
211:
102:
80:
1551:
1395:
1371:
1138:
1111:
1034:
999:
929:
894:
847:
Piomelli S (June 1973). "A micromethod for free erythrocyte porphyrins: the FEP test".
732:
705:
681:
654:
359:
345:
329:
321:
268:
1693:
1670:
1579:
1573:
1497:
1466:
1326:
981:
91:
1089:
833:
704:
Casanova-González MJ, Trapero-Marugán M, Jones EA, Moreno-Otero R (September 2010).
1591:
1271:
1229:
639:
592:
488:
471:
158:
1024:
919:
817:
1569:
1266:
773:
756:
344:
Measurement of zinc protoporphyrin in red cells has been used for screening for
1587:
1443:
1349:
1308:
1256:
1073:
965:
256:
1128:
722:
1386:
1358:
1251:
653:
Mei, Z; Flores-Ayala, RC; Grummer-Strawn, LM; Brittenham, GM (31 May 2017).
532:
515:
1187:
1147:
1081:
1043:
973:
938:
741:
690:
631:
623:
541:
497:
1179:
860:
825:
584:
1647:
1276:
1197:
782:
384:
1543:
576:
145:
671:
1425:
1419:
1413:
1407:
403:
is that all of these conditions can be considered worth discovering.
267:
Except where otherwise noted, data are given for materials in their
23:
706:"Liver disease and erythropoietic protoporphyria: a concise review"
119:
755:
Blumberg WE, Eisinger J, Lamola AA, Zuckerman DM (February 1977).
71:
998:
Wang S, Hannafon BN, Lind SE, Ding WQ (2015-05-22). Tan M (ed.).
1403:
325:
110:
1201:
557:
International
Archives of Occupational and Environmental Health
195:
410:
285:
1661:
1638:
1617:
1542:
1496:
1487:
1457:
1394:
1385:
1357:
1348:
1307:
1285:
1236:
514:Martin CJ, Werntz CL, Ducatman AM (December 2004).
1110:Yin H, Fang J, Liao L, Maeda H, Su Q (June 2014).
472:"Zinc protoporphyrin: A metabolite with a mission"
888:
886:
884:
882:
880:
878:
876:
874:
872:
870:
430:ZnPP has been investigated for cancer therapies.
409:ZnPP is finding a new use as a drug in combined
157:
849:The Journal of Laboratory and Clinical Medicine
316:) refers to coordination complexes of zinc and
59:
604:
602:
509:
507:
461:
459:
457:
455:
1213:
1161:
1159:
1157:
8:
1168:Cancer Biotherapy & Radiopharmaceuticals
1055:
1053:
993:
991:
1105:
1103:
1101:
1099:
1493:
1391:
1354:
1291:
1244:
1220:
1206:
1198:
210:
101:
15:
1137:
1127:
1033:
1023:
928:
918:
772:
731:
721:
680:
670:
531:
487:
177:
399:The virtue of elevated ZPP testing as a
451:
206:
135:
92:
79:
7:
148:
118:
14:
710:World Journal of Gastroenterology
275:
22:
271:(at 25 °C , 100 kPa).
1:
391:erythropoietic protoporphyria
1025:10.1371/journal.pone.0127413
920:10.1371/journal.pone.0034994
818:10.1126/science.186.4167.936
489:10.1093/clinchem/45.12.2060
328:production is inhibited by
261:626.032 g/mol
1721:
1294:
1247:
1074:10.1007/s13277-012-0336-0
966:10.1007/s11095-014-1313-7
774:10.1093/clinchem/23.2.270
380:anemia of chronic disease
265:
222:
43:
35:
30:
21:
1434:Magnesium protoporphyrin
1129:10.1186/1471-2407-14-436
723:10.3748/wjg.v16.i36.4526
954:Pharmaceutical Research
757:"The hematofluorometer"
395:Diverse types of cancer
624:10.1542/peds.2006-0156
38:Zinc protoporphyrin IX
1534:Protoporphyrinogen IX
1180:10.1089/cbr.2010.0939
533:10.1093/occmed/kqh123
520:Occupational Medicine
466:Labbé RF, Vreman HJ,
1627:Bacteriochlorophyll
1606:Bacteriochlorophyll
767:(2 PT. 1): 270–274.
438:Structural chemistry
375:sideroblastic anemia
17:Zinc protoporphyrin
1640:Isobacteriochlorins
1475:Protochlorophyllide
1449:Zinc protoporphyrin
1016:2015PLoSO..1027413W
911:2012PLoSO...734994K
810:1974Sci...186..936L
569:1987IAOEH..59..613V
310:Zinc protoporphyrin
137:zinc+protoporphyrin
18:
1520:Coproporphyrinogen
761:Clinical Chemistry
577:10.1007/BF00377923
476:Clinical Chemistry
426:For cancer therapy
370:sickle cell anemia
332:and/or by lack of
298:Infobox references
16:
1687:
1686:
1683:
1682:
1679:
1678:
1483:
1482:
1439:Protoporphyrin IX
1367:Adenosylcobalamin
1344:
1343:
1340:
1339:
1317:Phycoerythrobilin
804:(4167): 936–938.
672:10.3390/nu9060557
482:(12): 2060–2072.
470:(December 1999).
318:protoporphyrin IX
306:Chemical compound
304:
303:
191:CompTox Dashboard
1712:
1653:Sirohydrochlorin
1619:Bacteriochlorins
1506:Uroporphyrinogen
1494:
1392:
1355:
1299:Phytochromobilin
1292:
1245:
1222:
1215:
1208:
1199:
1192:
1191:
1163:
1152:
1151:
1141:
1131:
1107:
1094:
1093:
1068:(4): 1031–1038.
1057:
1048:
1047:
1037:
1027:
995:
986:
985:
960:(8): 2124–2139.
949:
943:
942:
932:
922:
890:
865:
864:
844:
838:
837:
793:
787:
786:
776:
752:
746:
745:
735:
725:
701:
695:
694:
684:
674:
650:
644:
643:
606:
597:
596:
552:
546:
545:
535:
511:
502:
501:
491:
463:
411:cancer therapies
340:Clinical utility
288:
282:
279:
278:
230:Chemical formula
215:
214:
199:
197:
181:
161:
150:
139:
122:
105:
94:
83:
63:
26:
19:
1720:
1719:
1715:
1714:
1713:
1711:
1710:
1709:
1690:
1689:
1688:
1675:
1657:
1634:
1613:
1538:
1489:
1479:
1459:Phytoporphyrins
1453:
1396:Protoporphyrins
1381:
1377:Methylcobalamin
1336:
1332:Phycoviolobilin
1322:Phycocyanobilin
1303:
1281:
1262:Stercobilinogen
1240:
1232:
1226:
1196:
1195:
1165:
1164:
1155:
1109:
1108:
1097:
1059:
1058:
1051:
1010:(5): e0127413.
997:
996:
989:
951:
950:
946:
892:
891:
868:
846:
845:
841:
795:
794:
790:
754:
753:
749:
716:(36): 4526–31.
703:
702:
698:
652:
651:
647:
608:
607:
600:
554:
553:
549:
513:
512:
505:
465:
464:
453:
448:
440:
428:
419:
365:iron deficiency
350:iron deficiency
342:
322:red blood cells
307:
300:
295:
294:
293: ?)
284:
280:
276:
272:
250:
246:
242:
238:
232:
218:
200:
193:
184:
164:
151:
125:
86:
66:
53:
39:
12:
11:
5:
1718:
1716:
1708:
1707:
1702:
1692:
1691:
1685:
1684:
1681:
1680:
1677:
1676:
1674:
1673:
1667:
1665:
1659:
1658:
1656:
1655:
1650:
1644:
1642:
1636:
1635:
1633:
1632:
1623:
1621:
1615:
1614:
1612:
1611:
1603:
1585:
1567:
1552:Chlorophyllide
1548:
1546:
1540:
1539:
1537:
1536:
1531:
1517:
1502:
1500:
1498:Porphyrinogens
1491:
1485:
1484:
1481:
1480:
1478:
1477:
1472:
1463:
1461:
1455:
1454:
1452:
1451:
1446:
1441:
1436:
1431:
1400:
1398:
1389:
1383:
1382:
1380:
1379:
1374:
1372:Cyanocobalamin
1369:
1363:
1361:
1352:
1346:
1345:
1342:
1341:
1338:
1337:
1335:
1334:
1329:
1324:
1319:
1313:
1311:
1305:
1304:
1302:
1301:
1295:
1289:
1283:
1282:
1280:
1279:
1274:
1269:
1264:
1259:
1254:
1248:
1242:
1234:
1233:
1227:
1225:
1224:
1217:
1210:
1202:
1194:
1193:
1174:(5): 639–645.
1153:
1095:
1062:Tumour Biology
1049:
987:
944:
866:
855:(6): 932–940.
839:
788:
747:
696:
645:
618:(1): 224–232.
598:
563:(6): 613–621.
547:
526:(8): 587–591.
503:
450:
449:
447:
444:
439:
436:
427:
424:
418:
415:
397:
396:
393:
388:
382:
377:
372:
367:
362:
360:lead poisoning
346:lead poisoning
341:
338:
305:
302:
301:
296:
274:
273:
269:standard state
266:
263:
262:
259:
253:
252:
248:
244:
240:
236:
233:
228:
225:
224:
220:
219:
217:
216:
208:DTXSID80274823
203:
201:
189:
186:
185:
183:
182:
174:
172:
166:
165:
163:
162:
154:
152:
144:
141:
140:
133:
127:
126:
124:
123:
115:
113:
107:
106:
96:
88:
87:
85:
84:
76:
74:
68:
67:
65:
64:
56:
54:
49:
46:
45:
41:
40:
37:
33:
32:
28:
27:
13:
10:
9:
6:
4:
3:
2:
1717:
1706:
1703:
1701:
1698:
1697:
1695:
1672:
1671:Cofactor F430
1669:
1668:
1666:
1664:
1660:
1654:
1651:
1649:
1646:
1645:
1643:
1641:
1637:
1631:
1630:
1625:
1624:
1622:
1620:
1616:
1610:
1609:
1604:
1601:
1600:
1595:
1594:
1589:
1586:
1583:
1582:
1577:
1576:
1571:
1568:
1565:
1564:
1559:
1558:
1553:
1550:
1549:
1547:
1545:
1541:
1535:
1532:
1529:
1525:
1521:
1518:
1515:
1511:
1507:
1504:
1503:
1501:
1499:
1495:
1492:
1486:
1476:
1473:
1471:
1470:
1465:
1464:
1462:
1460:
1456:
1450:
1447:
1445:
1442:
1440:
1437:
1435:
1432:
1429:
1428:
1423:
1422:
1417:
1416:
1411:
1410:
1405:
1402:
1401:
1399:
1397:
1393:
1390:
1388:
1384:
1378:
1375:
1373:
1370:
1368:
1365:
1364:
1362:
1360:
1356:
1353:
1351:
1347:
1333:
1330:
1328:
1327:Phycourobilin
1325:
1323:
1320:
1318:
1315:
1314:
1312:
1310:
1306:
1300:
1297:
1296:
1293:
1290:
1288:
1284:
1278:
1275:
1273:
1270:
1268:
1265:
1263:
1260:
1258:
1255:
1253:
1250:
1249:
1246:
1243:
1239:
1235:
1231:
1230:tetrapyrroles
1223:
1218:
1216:
1211:
1209:
1204:
1203:
1200:
1189:
1185:
1181:
1177:
1173:
1169:
1162:
1160:
1158:
1154:
1149:
1145:
1140:
1135:
1130:
1125:
1121:
1117:
1113:
1106:
1104:
1102:
1100:
1096:
1091:
1087:
1083:
1079:
1075:
1071:
1067:
1063:
1056:
1054:
1050:
1045:
1041:
1036:
1031:
1026:
1021:
1017:
1013:
1009:
1005:
1001:
994:
992:
988:
983:
979:
975:
971:
967:
963:
959:
955:
948:
945:
940:
936:
931:
926:
921:
916:
912:
908:
905:(4): e34994.
904:
900:
896:
889:
887:
885:
883:
881:
879:
877:
875:
873:
871:
867:
862:
858:
854:
850:
843:
840:
835:
831:
827:
823:
819:
815:
811:
807:
803:
799:
792:
789:
784:
780:
775:
770:
766:
762:
758:
751:
748:
743:
739:
734:
729:
724:
719:
715:
711:
707:
700:
697:
692:
688:
683:
678:
673:
668:
664:
660:
656:
649:
646:
641:
637:
633:
629:
625:
621:
617:
613:
605:
603:
599:
594:
590:
586:
582:
578:
574:
570:
566:
562:
558:
551:
548:
543:
539:
534:
529:
525:
521:
517:
510:
508:
504:
499:
495:
490:
485:
481:
477:
473:
469:
462:
460:
458:
456:
452:
445:
443:
437:
435:
431:
425:
423:
416:
414:
412:
407:
404:
402:
394:
392:
389:
386:
383:
381:
378:
376:
373:
371:
368:
366:
363:
361:
358:
357:
356:
353:
351:
347:
339:
337:
335:
331:
327:
323:
319:
315:
311:
299:
292:
287:
270:
264:
260:
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255:
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234:
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202:
192:
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155:
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143:
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138:
134:
132:
129:
128:
121:
117:
116:
114:
112:
109:
108:
104:
100:
97:
95:
93:ECHA InfoCard
90:
89:
82:
78:
77:
75:
73:
70:
69:
62:
58:
57:
55:
52:
48:
47:
42:
34:
29:
25:
20:
1628:
1607:
1598:
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1467:Chlorophyll
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1272:Urobilinogen
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44:Identifiers
36:Other names
1705:Blood cells
1570:Chlorophyll
1309:Phycobilins
1287:Phytobilins
1267:Stercobilin
223:Properties
99:100.035.853
81:CHEBI:28783
1700:Porphyrins
1694:Categories
1588:Pheophytin
1490:porphyrins
1444:Pterobilin
1387:Porphyrins
1359:Corrinoids
1350:Macrocycle
1257:Biliverdin
1122:(1): 436.
1116:BMC Cancer
665:(6): 557.
612:Pediatrics
446:References
348:. and for
257:Molar mass
179:LNV3FKZ7GR
61:15442-64-5
51:CAS Number
1252:Bilirubin
1228:Types of
982:254885235
659:Nutrients
251:Zn
1663:Corphins
1648:Siroheme
1544:Chlorins
1277:Urobilin
1241:(Linear)
1188:21950555
1148:24927633
1090:18067203
1082:22302482
1044:26000787
1004:PLOS ONE
974:24558012
939:22514698
899:PLOS ONE
834:24011145
742:20857522
691:28561801
632:16818569
542:15576877
498:10585337
387:exposure
385:vanadium
1488:Reduced
1238:Bilanes
1139:4075569
1035:4441374
1012:Bibcode
930:3325916
907:Bibcode
861:4710372
826:4469690
806:Bibcode
798:Science
733:2945483
682:5490536
640:8050501
593:7583183
585:3679557
565:Bibcode
417:History
291:what is
289: (
146:PubChem
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401:screen
286:verify
283:
120:C03184
31:Names
1086:S2CID
978:S2CID
830:S2CID
636:S2CID
589:S2CID
324:when
159:27287
72:ChEBI
1404:Heme
1184:PMID
1144:PMID
1078:PMID
1040:PMID
970:PMID
935:PMID
857:PMID
822:PMID
779:PMID
738:PMID
687:PMID
628:PMID
581:PMID
538:PMID
494:PMID
334:iron
330:lead
326:heme
170:UNII
131:MeSH
111:KEGG
1528:III
1514:III
1176:doi
1134:PMC
1124:doi
1070:doi
1030:PMC
1020:doi
962:doi
925:PMC
915:doi
814:doi
802:186
769:doi
728:PMC
718:doi
677:PMC
667:doi
620:doi
616:118
573:doi
528:doi
484:doi
314:ZPP
196:EPA
149:CID
1696::
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1578:,
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