PMID- 30845773
OWN - NLM
STAT- MEDLINE
DCOM- 20190822
LR  - 20200225
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 9
IP  - 3
DP  - 2019 Mar 6
TI  - [Pt(O,O'-acac)(gamma-acac)(DMS)] Induces Autophagy in Caki-1 Renal Cancer Cells.
LID - 10.3390/biom9030092 [doi]
LID - 92
AB  - We have demonstrated the cytotoxic effects of [Pt(O,O'-acac)(gamma-acac)(dimethyl 
      sulfide (DMS))] on various immortalized cell lines, in primary cultures, and in 
      murine xenograft models in vivo. Recently, we also showed that 
      [Pt(O,O'-acac)(gamma-acac)(DMS)] is able to kill Caki-1 renal cells both in vivo and 
      in vitro. In the present paper, apoptotic and autophagic effects of 
      [Pt(O,O'-acac)(gamma-acac)(DMS)] and cisplatin were studied and compared using Caki-1 
      cancerous renal cells. The effects of cisplatin include activation of caspases, 
      proteolysis of enzyme poly ADP ribose polymerase (PARP), control of apoptosis 
      modulators B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and 
      BH3-interacting domain death agonist (Bid), and cell cycle arrest in G2/M phase. 
      Conversely, [Pt(O,O'-acac)(gamma-acac)(DMS)] did not induce caspase activation, nor 
      chromatin condensation or DNA fragmentation. The effects of 
      [Pt(O,O'-acac)(gamma-acac)(DMS)] include microtubule-associated proteins 1A/1B light 
      chain 3B (LC3)-I to LC3-II conversion, Beclin-1 and Atg-3, -4, and -5 increase, 
      Bcl-2 decrease, and monodansylcadaverine accumulation in autophagic vacuoles. 
      [Pt(O,O'-acac)(gamma-acac)(DMS)] also modulated various kinases involved in 
      intracellular transduction regulating cell fate. [Pt(O,O'-acac)(gamma-acac)(DMS)] 
      inhibited the phosphorylation of mammalian target of rapmycin (mTOR), p70S6K, and 
      AKT, and increased the phosphorylation of c-Jun N-terminal kinase (JNK1/2), a 
      kinase activity pattern consistent with autophagy induction. In conclusion, while 
      in past reports the high cytotoxicity of [Pt(O,O'-acac)(gamma-acac)(DMS)] was always 
      attributed to its ability to trigger an apoptotic process, in this paper we show 
      that Caki-1 cells die as a result of the induction of a strong autophagic 
      process.
FAU - Antonaci, Giovanna
AU  - Antonaci G
AD  - Laboratory of Cell Physiology, Department of Biological and Environmental 
      Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, 
      Italy. giovanna.antonaci@unisalento.it.
FAU - Cossa, Luca Giulio
AU  - Cossa LG
AD  - Laboratory of Cell Physiology, Department of Biological and Environmental 
      Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, 
      Italy. lucagiulio.cossa@gmail.com.
FAU - Muscella, Antonella
AU  - Muscella A
AD  - Laboratory of Cell Pathology, Department of Biological and Environmental Sciences 
      and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy. 
      antonella.muscella@unisalento.it.
FAU - Vetrugno, Carla
AU  - Vetrugno C
AD  - Laboratory of Cell Pathology, Department of Biological and Environmental Sciences 
      and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy. 
      santo.marsigliante@unisalento.it.
FAU - De Pascali, Sandra Angelica
AU  - De Pascali SA
AD  - Laboratory of General Inorganic Chemistry, Department of Biological and 
      Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 
      73100 Lecce, Italy. sandra.depascali@unisalento.it.
FAU - Fanizzi, Francesco Paolo
AU  - Fanizzi FP
AD  - Laboratory of General Inorganic Chemistry, Department of Biological and 
      Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 
      73100 Lecce, Italy. fp.fanizzi@unisalento.it.
FAU - Marsigliante, Santo
AU  - Marsigliante S
AD  - Laboratory of Cell Physiology, Department of Biological and Environmental 
      Sciences and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, 
      Italy. sandra.depascali@unisalento.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190306
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Organoplatinum Compounds)
RN  - 0 (Pt(O,O'-acac)(gamma-acac)(DMS))
RN  - Renal cell carcinoma 1
MH  - Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology
MH  - Autophagy/*drug effects
MH  - Carcinoma, Renal Cell/*drug therapy/pathology
MH  - Cell Cycle/drug effects
MH  - Cell Proliferation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Organoplatinum Compounds/chemical synthesis/chemistry/*pharmacology
MH  - Structure-Activity Relationship
MH  - Tumor Cells, Cultured
PMC - PMC6468382
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - cancerous renal cells
OT  - cisplatin
COIS- The authors declare no conflict of interest.
EDAT- 2019/03/09 06:00
MHDA- 2019/08/23 06:00
PMCR- 2019/03/01
CRDT- 2019/03/09 06:00
PHST- 2019/01/24 00:00 [received]
PHST- 2019/02/23 00:00 [revised]
PHST- 2019/02/26 00:00 [accepted]
PHST- 2019/03/09 06:00 [entrez]
PHST- 2019/03/09 06:00 [pubmed]
PHST- 2019/08/23 06:00 [medline]
PHST- 2019/03/01 00:00 [pmc-release]
AID - biom9030092 [pii]
AID - biomolecules-09-00092 [pii]
AID - 10.3390/biom9030092 [doi]
PST - epublish
SO  - Biomolecules. 2019 Mar 6;9(3):92. doi: 10.3390/biom9030092.