Selected polyoxopalladates as promising and selective antitumor drug candidates
Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against hum...
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| Veröffentlicht in: | Journal of biological inorganic chemistry 2021-12, Vol.26 (8), p.957-971 |
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| creator | Isakovic, Andjelka M. Čolović, Mirjana B. Ma, Tian Ma, Xiang Jeremic, Marija Gerić, Marko Gajski, Goran Misirlic-Dencic, Sonja Kortz, Ulrich Krstić, Danijela |
| description | Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na
8
[Pd
13
As
8
O
34
(OH)
6
]·42H
2
O (
Pd
13
), Na
4
[SrPd
12
O
6
(OH)
3
(PhAsO
3
)
6
(OAc)
3
]·2NaOAc·32H
2
O (
SrPd
12
), Na
6
[Pd
13
(AsPh)
8
O
32
]·23H
2
O (
Pd
13
L
), Na
12
[SnO
8
Pd
12
(PO
4
)
8
]·43H
2
O (
SnPd
12
)
,
and Na
12
[PbO
8
Pd
12
(PO
4
)
8
]·38H
2
O (
PbPd
12
)), as the largest subset of PONMs. A pure inorganic,
Pd
13
, was found as the most potent and selective antineuroblastoma agent with IC
50
values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC
50
values (µM) for 24/48 h treatment with
SrPd
12
and
Pd
13
L
were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas
SnPd
12
and
PbPd
12
did not remarkably affect the SH-SY5Y viability
(
IC
50
> > 100 µM).
Pd
13
caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly,
Pd
13
demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary,
SrPd
12
and
Pd
13
L
at concentrations ≥ 1/3 IC
50
(24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control.
SnPd
12
and
PbPd
12,
previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.
Graphic abstract |
| doi_str_mv | 10.1007/s00775-021-01905-4 |
| format | Article |
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8
[Pd
13
As
8
O
34
(OH)
6
]·42H
2
O (
Pd
13
), Na
4
[SrPd
12
O
6
(OH)
3
(PhAsO
3
)
6
(OAc)
3
]·2NaOAc·32H
2
O (
SrPd
12
), Na
6
[Pd
13
(AsPh)
8
O
32
]·23H
2
O (
Pd
13
L
), Na
12
[SnO
8
Pd
12
(PO
4
)
8
]·43H
2
O (
SnPd
12
)
,
and Na
12
[PbO
8
Pd
12
(PO
4
)
8
]·38H
2
O (
PbPd
12
)), as the largest subset of PONMs. A pure inorganic,
Pd
13
, was found as the most potent and selective antineuroblastoma agent with IC
50
values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC
50
values (µM) for 24/48 h treatment with
SrPd
12
and
Pd
13
L
were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas
SnPd
12
and
PbPd
12
did not remarkably affect the SH-SY5Y viability
(
IC
50
> > 100 µM).
Pd
13
caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly,
Pd
13
demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary,
SrPd
12
and
Pd
13
L
at concentrations ≥ 1/3 IC
50
(24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control.
SnPd
12
and
PbPd
12,
previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.
Graphic abstract</description><identifier>ISSN: 0949-8257</identifier><identifier>EISSN: 1432-1327</identifier><identifier>DOI: 10.1007/s00775-021-01905-4</identifier><identifier>PMID: 34549367</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Antitumor activity ; Apoptosis ; Autophagy ; Biochemistry ; Biomedical and Life Sciences ; Blood cells ; Caspase ; Cell activation ; Cell cycle ; Cell death ; Cell Line, Tumor ; Cell Survival ; Cisplatin ; Cisplatin - pharmacology ; Deoxyribonucleic acid ; DNA ; DNA fragmentation ; Drug development ; Humans ; Inorganic chemistry ; Life Sciences ; Metals ; Microbiology ; Mitochondria ; Neuroblastoma - drug therapy ; Neuroblasts ; Original Paper ; Peripheral blood ; Phagocytosis ; Toxicity ; Tumors</subject><ispartof>Journal of biological inorganic chemistry, 2021-12, Vol.26 (8), p.957-971</ispartof><rights>Society for Biological Inorganic Chemistry (SBIC) 2021</rights><rights>2021. Society for Biological Inorganic Chemistry (SBIC).</rights><rights>Society for Biological Inorganic Chemistry (SBIC) 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-fba069b87c83a514a1ef4cfe01da851305c2087207769177e8450b9cf2dcf6443</citedby><cites>FETCH-LOGICAL-c375t-fba069b87c83a514a1ef4cfe01da851305c2087207769177e8450b9cf2dcf6443</cites><orcidid>0000-0002-1886-1453 ; 0000-0002-8635-4701 ; 0000-0002-5472-3058 ; 0000-0002-5886-4106 ; 0000-0001-5270-709X ; 0000-0001-5037-9985 ; 0000-0002-9192-8087</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00775-021-01905-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00775-021-01905-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34549367$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Isakovic, Andjelka M.</creatorcontrib><creatorcontrib>Čolović, Mirjana B.</creatorcontrib><creatorcontrib>Ma, Tian</creatorcontrib><creatorcontrib>Ma, Xiang</creatorcontrib><creatorcontrib>Jeremic, Marija</creatorcontrib><creatorcontrib>Gerić, Marko</creatorcontrib><creatorcontrib>Gajski, Goran</creatorcontrib><creatorcontrib>Misirlic-Dencic, Sonja</creatorcontrib><creatorcontrib>Kortz, Ulrich</creatorcontrib><creatorcontrib>Krstić, Danijela</creatorcontrib><title>Selected polyoxopalladates as promising and selective antitumor drug candidates</title><title>Journal of biological inorganic chemistry</title><addtitle>J Biol Inorg Chem</addtitle><addtitle>J Biol Inorg Chem</addtitle><description>Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na
8
[Pd
13
As
8
O
34
(OH)
6
]·42H
2
O (
Pd
13
), Na
4
[SrPd
12
O
6
(OH)
3
(PhAsO
3
)
6
(OAc)
3
]·2NaOAc·32H
2
O (
SrPd
12
), Na
6
[Pd
13
(AsPh)
8
O
32
]·23H
2
O (
Pd
13
L
), Na
12
[SnO
8
Pd
12
(PO
4
)
8
]·43H
2
O (
SnPd
12
)
,
and Na
12
[PbO
8
Pd
12
(PO
4
)
8
]·38H
2
O (
PbPd
12
)), as the largest subset of PONMs. A pure inorganic,
Pd
13
, was found as the most potent and selective antineuroblastoma agent with IC
50
values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC
50
values (µM) for 24/48 h treatment with
SrPd
12
and
Pd
13
L
were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas
SnPd
12
and
PbPd
12
did not remarkably affect the SH-SY5Y viability
(
IC
50
> > 100 µM).
Pd
13
caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly,
Pd
13
demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary,
SrPd
12
and
Pd
13
L
at concentrations ≥ 1/3 IC
50
(24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control.
SnPd
12
and
PbPd
12,
previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.
Graphic abstract</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Blood cells</subject><subject>Caspase</subject><subject>Cell activation</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival</subject><subject>Cisplatin</subject><subject>Cisplatin - pharmacology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA fragmentation</subject><subject>Drug development</subject><subject>Humans</subject><subject>Inorganic chemistry</subject><subject>Life Sciences</subject><subject>Metals</subject><subject>Microbiology</subject><subject>Mitochondria</subject><subject>Neuroblastoma - drug therapy</subject><subject>Neuroblasts</subject><subject>Original Paper</subject><subject>Peripheral blood</subject><subject>Phagocytosis</subject><subject>Toxicity</subject><subject>Tumors</subject><issn>0949-8257</issn><issn>1432-1327</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EoqXwAyxQJNaG8SuOl6jiJVXqAlhbjuNUqfLCThD8PW5TYMfGljVn7owPQpcEbgiAvA3xkAIDJRiIAoH5EZoTzigmjMpjNAfFFc6okDN0FsIWAJgg4hTNGBdcsVTO0frF1c4Orkj6rv7qPrve1LUpzOBCYkLS-66pQtVuEtMWSdiz1YeLr6EaxqbzSeHHTWJjtdo3naOT0tTBXRzuBXp7uH9dPuHV-vF5ebfClkkx4DI3kKo8kzZjRhBuiCu5LR2QwmSCMBCWQiZp_GCqiJQu4wJyZUta2DLlnC3Q9ZQbN3wfXRj0tht9G0dqKjJFFKMgIkUnyvouBO9K3fuqMf5LE9A7h3pyqKNDvXeod9FXh-gxb1zx2_IjLQJsAkIstRvn_2b_E_sNusl8vw</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Isakovic, Andjelka M.</creator><creator>Čolović, Mirjana B.</creator><creator>Ma, Tian</creator><creator>Ma, Xiang</creator><creator>Jeremic, Marija</creator><creator>Gerić, Marko</creator><creator>Gajski, Goran</creator><creator>Misirlic-Dencic, Sonja</creator><creator>Kortz, Ulrich</creator><creator>Krstić, Danijela</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-1886-1453</orcidid><orcidid>https://orcid.org/0000-0002-8635-4701</orcidid><orcidid>https://orcid.org/0000-0002-5472-3058</orcidid><orcidid>https://orcid.org/0000-0002-5886-4106</orcidid><orcidid>https://orcid.org/0000-0001-5270-709X</orcidid><orcidid>https://orcid.org/0000-0001-5037-9985</orcidid><orcidid>https://orcid.org/0000-0002-9192-8087</orcidid></search><sort><creationdate>20211201</creationdate><title>Selected polyoxopalladates as promising and selective antitumor drug candidates</title><author>Isakovic, Andjelka M. ; Čolović, Mirjana B. ; Ma, Tian ; Ma, Xiang ; Jeremic, Marija ; Gerić, Marko ; Gajski, Goran ; Misirlic-Dencic, Sonja ; Kortz, Ulrich ; Krstić, Danijela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-fba069b87c83a514a1ef4cfe01da851305c2087207769177e8450b9cf2dcf6443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Blood cells</topic><topic>Caspase</topic><topic>Cell activation</topic><topic>Cell cycle</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival</topic><topic>Cisplatin</topic><topic>Cisplatin - pharmacology</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA fragmentation</topic><topic>Drug development</topic><topic>Humans</topic><topic>Inorganic chemistry</topic><topic>Life Sciences</topic><topic>Metals</topic><topic>Microbiology</topic><topic>Mitochondria</topic><topic>Neuroblastoma - drug therapy</topic><topic>Neuroblasts</topic><topic>Original Paper</topic><topic>Peripheral blood</topic><topic>Phagocytosis</topic><topic>Toxicity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Isakovic, Andjelka M.</creatorcontrib><creatorcontrib>Čolović, Mirjana B.</creatorcontrib><creatorcontrib>Ma, Tian</creatorcontrib><creatorcontrib>Ma, Xiang</creatorcontrib><creatorcontrib>Jeremic, Marija</creatorcontrib><creatorcontrib>Gerić, Marko</creatorcontrib><creatorcontrib>Gajski, Goran</creatorcontrib><creatorcontrib>Misirlic-Dencic, Sonja</creatorcontrib><creatorcontrib>Kortz, Ulrich</creatorcontrib><creatorcontrib>Krstić, Danijela</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of biological inorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Isakovic, Andjelka M.</au><au>Čolović, Mirjana B.</au><au>Ma, Tian</au><au>Ma, Xiang</au><au>Jeremic, Marija</au><au>Gerić, Marko</au><au>Gajski, Goran</au><au>Misirlic-Dencic, Sonja</au><au>Kortz, Ulrich</au><au>Krstić, Danijela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selected polyoxopalladates as promising and selective antitumor drug candidates</atitle><jtitle>Journal of biological inorganic chemistry</jtitle><stitle>J Biol Inorg Chem</stitle><addtitle>J Biol Inorg Chem</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>26</volume><issue>8</issue><spage>957</spage><epage>971</epage><pages>957-971</pages><issn>0949-8257</issn><eissn>1432-1327</eissn><abstract>Polyoxo-noble-metalates (PONMs), a class of molecular noble metal-oxo nanoclusters that combine features of both polyoxometalates and noble metals, are a promising platform for the development of next-generation antitumor metallodrugs. This study aimed to evaluate the antitumor potential against human neuroblastoma cells (SH-SY5Y), as well as toxicity towards healthy human peripheral blood cells (HPBCs), of five polyoxopalladates(II): (Na
8
[Pd
13
As
8
O
34
(OH)
6
]·42H
2
O (
Pd
13
), Na
4
[SrPd
12
O
6
(OH)
3
(PhAsO
3
)
6
(OAc)
3
]·2NaOAc·32H
2
O (
SrPd
12
), Na
6
[Pd
13
(AsPh)
8
O
32
]·23H
2
O (
Pd
13
L
), Na
12
[SnO
8
Pd
12
(PO
4
)
8
]·43H
2
O (
SnPd
12
)
,
and Na
12
[PbO
8
Pd
12
(PO
4
)
8
]·38H
2
O (
PbPd
12
)), as the largest subset of PONMs. A pure inorganic,
Pd
13
, was found as the most potent and selective antineuroblastoma agent with IC
50
values (µM) of 7.2 ± 2.2 and 4.4 ± 1.2 for 24 and 48 h treatment, respectively, even lower than cisplatin (28.4 ± 7.4 and 11.6 ± 0.8). The obtained IC
50
values (µM) for 24/48 h treatment with
SrPd
12
and
Pd
13
L
were 75.8 ± 6.7/76.7 ± 22.9 and 63.8 ± 3.6/21.4 ± 10.8, respectively, whereas
SnPd
12
and
PbPd
12
did not remarkably affect the SH-SY5Y viability
(
IC
50
> > 100 µM).
Pd
13
caused depolarisation of inner mitochondrial membrane prior to superoxide ion hyperproduction, followed by caspase activation, DNA fragmentation and cell cycle arrest, all hallmarks of apoptotic cell death, and accompanied by an increase in acidic vesicles content, suggestive of autophagy induction. Importantly,
Pd
13
demonstrated the antitumor effect at concentrations not cytogenotoxic for normal HPBCs. On the contrary,
SrPd
12
and
Pd
13
L
at concentrations ≥ 1/3 IC
50
(24 h) decreased HPBC viability and increased % tail DNA up to 42% and 3.05 times, respectively, related to control.
SnPd
12
and
PbPd
12,
previously confirmed promising antileukemic agents, did not exhibit cytogenotoxicity to HPBCs, and thus could be regarded as tumor cell specific and selective drug candidates.
Graphic abstract</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>34549367</pmid><doi>10.1007/s00775-021-01905-4</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-1886-1453</orcidid><orcidid>https://orcid.org/0000-0002-8635-4701</orcidid><orcidid>https://orcid.org/0000-0002-5472-3058</orcidid><orcidid>https://orcid.org/0000-0002-5886-4106</orcidid><orcidid>https://orcid.org/0000-0001-5270-709X</orcidid><orcidid>https://orcid.org/0000-0001-5037-9985</orcidid><orcidid>https://orcid.org/0000-0002-9192-8087</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0949-8257 |
| ispartof | Journal of biological inorganic chemistry, 2021-12, Vol.26 (8), p.957-971 |
| issn | 0949-8257 1432-1327 |
| language | eng |
| recordid | cdi_proquest_journals_2589193205 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Antitumor activity Apoptosis Autophagy Biochemistry Biomedical and Life Sciences Blood cells Caspase Cell activation Cell cycle Cell death Cell Line, Tumor Cell Survival Cisplatin Cisplatin - pharmacology Deoxyribonucleic acid DNA DNA fragmentation Drug development Humans Inorganic chemistry Life Sciences Metals Microbiology Mitochondria Neuroblastoma - drug therapy Neuroblasts Original Paper Peripheral blood Phagocytosis Toxicity Tumors |
| title | Selected polyoxopalladates as promising and selective antitumor drug candidates |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T03%3A22%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Selected%20polyoxopalladates%20as%20promising%20and%20selective%20antitumor%20drug%20candidates&rft.jtitle=Journal%20of%20biological%20inorganic%20chemistry&rft.au=Isakovic,%20Andjelka%20M.&rft.date=2021-12-01&rft.volume=26&rft.issue=8&rft.spage=957&rft.epage=971&rft.pages=957-971&rft.issn=0949-8257&rft.eissn=1432-1327&rft_id=info:doi/10.1007/s00775-021-01905-4&rft_dat=%3Cproquest_cross%3E2589193205%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2589193205&rft_id=info:pmid/34549367&rfr_iscdi=true |