Naproxen platinum(<scp>iv</scp>) hybrids inhibiting cycloxygenases and matrix metalloproteinases and causing DNA damage: synthesis and biological evaluation as antitumor agents <i>in vitro</i> and <i>in vivo</i>

Chen, Yan; Wang, Qingpeng; Li, Zuojie; Liu, Zhifang; Zhao, Yanna; Zhang, Junfeng; Liu, Min; Wang, Zhengping; Li, Dacheng; Han, Jun

doi:10.1039/d0dt00424c

“…Both DNP and NP exhibited strong activity against ERα‐positive MCF‐7 cells and TNBC MDA‐MB‐231 cells, far more potent than CDDP. DNP displayed a superior cytotoxicity over NP, showing activity comparable to other analogues or NSAIDs‐Pt complexes [29–35, 37, 38] . The mixtures of CDDP and NPX exhibited less cytotoxicity than that of CDDP, suggesting that free NPX hardly contributed to the cytotoxicity and even antagonized CDDP.…”

Section: Resultsmentioning

confidence: 94%

“…For the sake of comparison, Pt IV complex with one axial NPX ligand, namely NP, was also prepared and investigated. In fact, the anticancer and antiinflammatory activities of NP have been studied recently; [37, 38] however, DNP has not been reported so far.…”

Section: Introductionmentioning

confidence: 99%

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

Jin

¹

,

Nafees

²

,

Sun

³

et al. 2020

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Breast cancer (BC) is one of the most common malignancies in women and often accompanied by inflammatory processes.Cyclooxygenase-2 (COX-2) playsavital role in the progression of BC,c orrelating with the expression of programmed death-ligand 1(PD-L1). Overexpression of PD-L1 contributes to the immune escape of cancer cells,a nd its blockade would stimulate anticancer immunity.T wo multispecific platinum(IV) complexes DNP and NP were prepared using non-steroidal antiinflammatory drug naproxen (NPX) as axial ligand(s) to inhibit the BC cells.D NP exhibited high cytotoxicity and antiinflammatory properties superior over NP, cisplatin and NPX;m oreover,i td isplayed potent antitumor activity and almost no general toxicity in mice bearing triplenegative breast cancer (TNBC). Mechanistic studies revealed that DNP could downregulate the expression of COX-2 and PD-L1 in vitro and vivo,inhibit the secretion of prostaglandin, reduce the expression of BC-associated protein BRD4 and phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), and block the oncogene c-Myc in BC cells.T hese findings demonstrate that DNP is capable of intervening in inflammatory,i mmune,a nd metastatic processes of BC,t hus presenting anew mechanism of action for anticancer platinum-(IV) complexes.T he multispecificity offers as pecial superiority for DNP to treat TNBC by combining chemotherapyand immunotherapyi none molecule.

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“…Fort he sake of comparison, Pt IV complex with one axial NPX ligand, namely NP,w as also prepared and investigated. In fact, the anticancer and antiinflammatory activities of NP have been studied recently; [37,38] however, DNP has not been reported so far.…”

Section: Introductionmentioning

confidence: 99%

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

Jin

¹

,

Nafees

²

,

Sun

³

et al. 2020

View full text Add to dashboard Cite

Breast cancer (BC) is one of the most common malignancies in women and often accompanied by inflammatory processes.Cyclooxygenase-2 (COX-2) playsavital role in the progression of BC,c orrelating with the expression of programmed death-ligand 1(PD-L1). Overexpression of PD-L1 contributes to the immune escape of cancer cells,a nd its blockade would stimulate anticancer immunity.T wo multispecific platinum(IV) complexes DNP and NP were prepared using non-steroidal antiinflammatory drug naproxen (NPX) as axial ligand(s) to inhibit the BC cells.D NP exhibited high cytotoxicity and antiinflammatory properties superior over NP, cisplatin and NPX;m oreover,i td isplayed potent antitumor activity and almost no general toxicity in mice bearing triplenegative breast cancer (TNBC). Mechanistic studies revealed that DNP could downregulate the expression of COX-2 and PD-L1 in vitro and vivo,inhibit the secretion of prostaglandin, reduce the expression of BC-associated protein BRD4 and phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), and block the oncogene c-Myc in BC cells.T hese findings demonstrate that DNP is capable of intervening in inflammatory,i mmune,a nd metastatic processes of BC,t hus presenting anew mechanism of action for anticancer platinum-(IV) complexes.T he multispecificity offers as pecial superiority for DNP to treat TNBC by combining chemotherapyand immunotherapyi none molecule.

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“…Our previous work reported a series of mono-naproxen platinum(IV) complexes with prominent antitumor activities, which showed great potential in inhibiting tumor migration by synergistic inhibition of COX-2 and matrix metalloproteinases (MMPs). 39 More recently, Guo and Wang’s group reported the efficient antitumor performance of dual naproxen platinum(IV) complex 2 . 40 It targeted COX-2 and PD-L1 via multiple pathways to significantly inhibit the immune escape of tumor cells and finally improve antitumor efficacy.…”

Section: Introductionmentioning

confidence: 99%

Albumin-encapsulated Nanoparticles of Naproxen Platinum(IV) Complexes with Inflammation Inhibitory Competence Displaying Effective Antitumor Activities in vitro and in vivo

Li¹,

Chen²,

Wang³

et al. 2021

IJN

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Background Platinum(IV) complexes with inflammation inhibitory properties are much favored in improving antitumor activities. Nanodrug-delivery system as a preferable measure for antitumor therapy are widely explored in platinum(IV) drug delivery. Purpose The aim for this study was to develop novel bovine serum albumin (BSA) nanoparticles (NPs) based on naproxen platinum(IV) complexes to display a synergistic antitumor mechanism targeting cyclooxygenase-2 (COX-2), metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS). Methods Herein, we reported the preparation of two BSA NPs of naproxen platinum(IV) complexes, and their antitumor activities were investigated in vitro and in vivo. Results Both NPs possessed relatively uniform size and good stability for 30 days in aqueous solution. They exhibited prominent antitumor activities in vitro, and showed great potential in reversing drug resistance. Furthermore, these two NPs played superior tumor growth suppression in vivo in contrast to the free compounds, which were comparable to that of cisplatin and oxaliplatin, but induced lower toxic influences than platinum(II) drugs especially to spleen and liver. Moreover, the naproxen platinum(IV) NPs could decrease tumor inflammation targeting COX-2, MMP-9 and iNOs, and decreasing NO production, which would be in favor of enhancing the antitumor competence, and reducing toxicity. Conclusion Taken together, BSA NPs of naproxen platinum(IV) complexes demonstrated a powerful antitumor efficacy in vitro and in vivo. The platinum(IV) NPs with inflammation inhibitory competence targeting multiple enzymes reported in this work afford a new strategy for the development of antitumor therapy to overcome drawbacks of clinical platinum(II) drugs.

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Naproxen platinum(iv) hybrids inhibiting cycloxygenases and matrix metalloproteinases and causing DNA damage: synthesis and biological evaluation as antitumor agents in vitro and in vivo

Abstract: Naproxen platinum(iv) hybrids display effective antitumor activities by inhibiting cycloxygenases and matrix metalloproteinases and by causing DNA damage.

Cited by 51 publications

References 50 publications

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

Multispecific Platinum(IV) Complex Deters Breast Cancer via Interposing Inflammation and Immunosuppression as an Inhibitor of COX‐2 and PD‐L1

Albumin-encapsulated Nanoparticles of Naproxen Platinum(IV) Complexes with Inflammation Inhibitory Competence Displaying Effective Antitumor Activities in vitro and in vivo

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