The ligation of aspirin to cisplatin demonstrates significant synergistic effects on tumor cells

Cheng, Qinqin; Shi, Hongdong; Wang, Hongxia; Min, Yuanzeng; Wang, Jun; Liu, Yangzhong

doi:10.1039/c4cc00419a

Cited by 166 publications

(105 citation statements)

References 22 publications

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“…Upon entry of tumor cells, either the released NSAIDs or even the intact conjugates could lead to COX inhibition and thus decrease tumor-associated inflammation, as shown for a similar conjugate between cisplatin and aspirin. [10a] …”

Section: Resultsmentioning

confidence: 99%

“…The conjugates are among the most active compounds of the class of platinum(IV) carboxylato complexes, most of which exhibited potencies similar to that of cisplatin. [10, 15c, d, 26a, 31] Only few of the previously reported derivatives have shown highly increased cytotoxicities, with activities in the sub-micromolar range. [15d, 32] Especially potent, however, are the benzoate derivatives, which resemble the structure of the ibuprofen conjugates and showed activities similar to 4 and 6 .…”

Section: Resultsmentioning

confidence: 99%

“…Consistently, combined treatment of the cancer cells with cisplatin and the respective NSAID (ratio 1:2) did not reveal any increase in cytotoxicity over that of cisplatin alone, [9] which was similarly observed for the combination of cisplatin with aspirin. [10a] Furthermore, the NSAIDs themselves did not reveal antitumor activity at pharmacological concentrations. [5c, 9] These findings are consistent with previous studies suggesting that the positive effects of COX inhibitors on the potency of antitumor agents are COX-2-independent.…”

Section: Resultsmentioning

confidence: 99%

“…Although less potent, the conjugate between cisplatin and aspirin also revealed an improved efficacy of the platinum drug. [10] …”

Section: Introductionmentioning

confidence: 99%

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Conjugation of Cisplatin Analogues and Cyclooxygenase Inhibitors to Overcome Cisplatin Resistance

et al. 2014

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Cyclooxygenase (COX) is an enzyme involved in tumorigenesis and is associated with tumor cell resistance against platinum-based antitumor drugs. Cisplatin analogues were conjugated with COX inhibitors (indomethacin, ibuprofen) to study the synergistic effects that were previously observed in combination treatments. The conjugates ensure concerted transport of both drugs into cells, and subsequent intracellular cleavage enables a dual-action mode. Whereas the platinum(II) complexes showed cytotoxicities similar to those of cisplatin, the platinum(IV) conjugates revealed highly increased cytotoxic activities and were able to completely overcome cisplatin-related resistance. Although some of the complexes are potent COX inhibitors, the conjugates appear to execute their cytotoxic action via COX-independent mechanisms. Instead, the increased lipophilicity and kinetic inertness of the conjugates seem to facilitate cellular accumulation of the platinum drugs and thus improve the efficacy of the antitumor agents. These conjugates are important tools for the elucidation of the direct influence of COX inhibitors on platinum-based anticancer drugs in tumor cells.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Although less potent, the conjugate between cisplatin and aspirin also revealed an improved efficacy of the platinum drug. [10] …”

Section: Introductionmentioning

confidence: 99%

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Conjugation of Cisplatin Analogues and Cyclooxygenase Inhibitors to Overcome Cisplatin Resistance

et al. 2014

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“…One approach is design and development of new Pt complexes that modulate the molecular process and pathways associated with tumor suppression. 8,9 Mitochondria represent interesting targets for drug development. A wide range of pathologies including cardiovascular disorders, 10 diabetes, 11 neurodegenerative diseases, 12,13 and cancers are related with mitochondrial dysfunction.…”

mentioning

confidence: 99%

Mitochondria-Localized Fluorescent BODIPY-Platinum Conjugate

Sun

Guan

Zheng

et al. 2015

ACS Med. Chem. Lett.

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A convenient synthesis of a BODIPY (1,3,5,7-tetramethyl-8-(4-pyridyl)-4,4′-difluoroboradiazaindacene) labeled platinum compound (BODIPY-Pt) was developed by direct conjugation of cisplatin with the pyridine group of BODIPY. The membrane permeability and selective uptake of BODIPY-Pt in the mitochondria was studied using confocal laser scanning microscopy (CLSM). The fluorescent BODIPYPt conjugate showed high cellular proliferation inhibition against human cervical carcinoma (HeLa) and human breast cancer (MCF-7) cells, with half maximal inhibitory concentrations (IC 50 ) of 27.37 and 12.14 μM, respectively. This work highlights the potential of using BODIPY labeled Pt compounds to realize the visualization of Pt distribution in living cells.

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Berplatin: A Conjugate of Berberine and Cisplatin Serving as a Potent Antitumor Agent with Distinctive Tumor Cell Uptake and Minimal Side Effects

Luo

Xiong³

et al. 2022

Advanced Therapeutics

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Design of Pt(IV) prodrugs with biologically active axial ligands is an excellent approach to overcome the disadvantages (nonspecific killing, side effects, and drug resistance) of conventional first‐line Pt(II)‐based chemotherapeutic drugs, such as cisplatin, carboplatin and oxaliplatin. The selection of ideal axial ligands is essential for the success of Pt(IV) drugs. Previously, that berberine exhibits great superiority in tumor selectivity is found with uncovered mechanisms. In this study, that berberine is specifically internalized and accumulated in tumors but not normal cells through endocytosis pathways is first disclosed. Therefore a new Pt(IV) prodrug of cisplatin bearing berberine as an axial ligand, named berplatin, is designed and synthesized. Different from cisplatin, berplatin can be effectively and selectively internalized into cancer cells, through macropinocytosis and caveolin‐1 (CAV‐1)‐dependent active endocytosis, and cleaved in intracellular reductive environments to generate cisplatin and berberine, which synergistically induces substantial DNA breaking, apoptosis and cell cycle arrest in both cisplatin‐sensitive and ‐resistant cancer cells. In vivo, berplatin manifests much higher antitumor activity and undetectable side effects compared to cisplatin. This study demonstrates that berplatin can serve as a potent Pt(IV) prodrug for the treatment of cisplatin‐sensitive and ‐resistant cancers with active uptake, excellent specificity, and minimal side effects.

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The ligation of aspirin to cisplatin demonstrates significant synergistic effects on tumor cells

Abstract: Asplatin, a fusion of aspirin and cisplatin, exhibits significant cytotoxicity in tumor cells and almost fully overcomes the drug resistance of cisplatin resistant cells. Asplatin is highly accumulated in cancer cells and is activated upon the reduction by ascorbic acid.

Cited by 166 publications

References 22 publications

Conjugation of Cisplatin Analogues and Cyclooxygenase Inhibitors to Overcome Cisplatin Resistance

Conjugation of Cisplatin Analogues and Cyclooxygenase Inhibitors to Overcome Cisplatin Resistance

Mitochondria-Localized Fluorescent BODIPY-Platinum Conjugate

Berplatin: A Conjugate of Berberine and Cisplatin Serving as a Potent Antitumor Agent with Distinctive Tumor Cell Uptake and Minimal Side Effects

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