Research Progress of Metal Anticancer Drugs

Bai, Yun; Aodeng, Gerile; Ga, Lu; Hai, Wenfeng; Ai, Jun

doi:10.3390/pharmaceutics15122750

Cited by 11 publications

(4 citation statements)

References 151 publications

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“…Lobaplatin (1,2-diaminomethylcyclobutane platinum(II) lactic acid), a third-generation CDDP derivative has found only regionally limited use as an anti-cancer agent in China. [86,87] Lobaplatin does not need to be hydrated like CDDP but its action is similar to CDDP in terms of DNA damage and cell apoptosis. Lobaplatin has played a reliable anti-tumour role in treating solid tumors such as lung cancer, nasopharyngeal cancer, breast cancer and gastric cancer.…”

Section: Lobaplatinmentioning

confidence: 99%

Cisplatin Resistance in Cancer Therapy: Causes and Overcoming Strategies

Shruthi,

Bhasker Shenoy

2024

ChemistrySelect

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Dr. S. Shruthi, Prof. Dr. K. Bhasker Shenoy. Cisplatin (CDDP) is the first metal‐based drug and has been a popular drug in the treatment of various types of cancer for decades. Cancer cell death is promoted by this platinum‐based drug by generating DNA adducts and activating apoptotic signaling pathways. The development of drug resistance is the foremost clinical concern that compromises its efficacy. The mechanism of CDDP resistance encompasses changes in drug influx and efflux, drug accumulation reduction, enhanced drug detoxification, and repair which may affect its therapeutic value. Researchers have paid significant attention to overcoming CDDP resistance, which provides an opportunity to enhance clinical outcomes. Combinational therapy, use of CDDP analogs, phytochemicals, nanoparticle‐mediated drug delivery, gene targeting and regulation of drug induced epigenetic changes are the specific regimens to overcome CDDP resistance and treatment burden. In this review, we summarize the mechanisms involved in CDDP resistance and strategies considered to overcome these hurdles concerning preclinical and clinical studies. This may provide insights into the further development of novel approaches to uproot CDDP resistance, to ascertain a safer and more effective cancer therapy.

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Section: Lobaplatinmentioning

confidence: 99%

Cisplatin Resistance in Cancer Therapy: Causes and Overcoming Strategies

Shruthi,

Bhasker Shenoy

2024

ChemistrySelect

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“…Cisplatin (cis-dichlorodiammine platinum (II), CDDP) is an important component of cancer chemotherapy, which is used as a single agent or in combination with other anti-neoplastic drugs, radiotherapy, and immunotherapy for the treatment of various types of cancer [ 1 , 2 ]. A significant challenge associated with CDDP-based chemotherapy is the occurrence of significant undesired toxic effects, notably nephro- and ototoxicity.…”

Section: Introductionmentioning

confidence: 99%

Modulating the Activity of the Human Organic Cation Transporter 2 Emerges as a Potential Strategy to Mitigate Unwanted Toxicities Associated with Cisplatin Chemotherapy

Hucke,

Kantauskaite,

Köpp

et al. 2024

IJMS

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Cisplatin (CDDP) stands out as an effective chemotherapeutic agent; however, its application is linked to the development of significant adverse effects, notably nephro- and ototoxicity. The human organic cation transporter 2 (hOCT2), found in abundance in the basolateral membrane domain of renal proximal tubules and the Corti organ, plays a crucial role in the initiation of nephro- and ototoxicity associated with CDDP by facilitating its uptake in kidney and ear cells. Given its limited presence in cancer cells, hOCT2 emerges as a potential druggable target for mitigating unwanted toxicities associated with CDDP. Potential strategies for mitigating CDDP toxicities include competing with the uptake of CDDP by hOCT2 or inhibiting hOCT2 activity through rapid regulation mediated by specific signaling pathways. This study investigated the interaction between the already approved cationic drugs disopyramide, imipramine, and orphenadrine with hOCT2 that is stably expressed in human embryonic kidney cells. Regarding disopyramide, its influence on CDDP cellular transport by hOCT2 was further characterized through inductively coupled plasma isotope dilution mass spectrometry. Additionally, its potential protective effects against cellular toxicity induced by CDDP were assessed using a cytotoxicity test. Given that hOCT2 is typically expressed in the basolateral membrane of polarized cells, with specific regulatory mechanisms, this work studied the regulation of hOCT2 that is stably expressed in Madin–Darby Canine Kidney (MDCK) cells. These cells were cultured in a matrix to induce the formation of cysts, exposing hOCT2 in the basolateral plasma membrane domain, which was freely accessible to experimental solutions. The study specifically tested the regulation of ASP+ uptake by hOCT2 in MDCK cysts through the inhibition of casein kinase II (CKII), calmodulin, or p56lck tyrosine kinase. Furthermore, the impact of this manipulation on the cellular toxicity induced by CDDP was examined using a cytotoxicity test. All three drugs—disopyramide, imipramine, and orphenadrine—demonstrated inhibition of ASP+ uptake, with IC50 values in the micromolar (µM) range. Notably, disopyramide produced a significant reduction in the CDDP cellular toxicity and platinum cellular accumulation when co-incubated with CDDP. The activity of hOCT2 in MDCK cysts experienced a significant down-regulation under inhibition of CKII, calmodulin, or p56lck tyrosine kinase. Interestingly, only the inhibition of p56lck tyrosine kinase demonstrated the capability to protect the cells against CDDP toxicity. In conclusion, certain interventions targeting hOCT2 have demonstrated the ability to reduce CDDP cytotoxicity, at least in vitro. Further investigations in in vivo systems are warranted to ascertain their potential applicability as co-treatments for mitigating undesired toxicities associated with CDDP in patients.

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“…Utilizing different metals in cancer therapy can potentially affect tumor cells differently and induce distinct molecular pathways compared to platinum-based drugs. Non-platinum-based compounds, including titanium, ruthenium, tin, palladium, and gold complexes, are in focus as potential anticancer agents [9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

(Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand

Ludwig,

Ranđelović,

Dimić

et al. 2024

Biomolecules

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The (pentamethylcyclopentadienyl)chloridoiridium(III) complex bearing a κP,κS-bonded Ph2PCH2CH2SPh ligand ([Ir(η5-C5Me5)Cl(Ph2P(CH2)2SPh-κP,κS)]PF6, (1)] was synthesized and characterized. Multinuclear (1H, 13C and 31P) NMR spectroscopy was employed for the determination of the structure. Moreover, SC-XRD confirmed the proposed structure belongs to the “piano stool” type. The Hirshfeld surface analysis outlined the most important intermolecular interactions in the structure. The crystallographic structure was optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,P,S,Cl)/LanL2DZ(Ir) level of theory. The applicability of this level was verified through a comparison of experimental and theoretical bond lengths and angles, and 1H and 13C NMR chemical shifts. The Natural Bond Orbital theory was used to identify and quantify the intramolecular stabilization interactions, especially those between donor atoms and Ir(III) ions. Complex 1 was tested on antitumor activity against five human tumor cell lines: MCF-7 breast adenocarcinoma, SW480 colon adenocarcinoma, 518A2 melanoma, 8505C human thyroid carcinoma and A253 submandibular carcinoma. Complex 1 showed superior antitumor activity against cisplatin-resistant MCF-7, SW480 and 8505C cell lines. The mechanism of tumoricidal action on 8505C cells indicates the involvement of caspase-induced apoptosis, accompanied by a considerable reduction in ROS/RNS and proliferation potential of treated cells.

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Research Progress of Metal Anticancer Drugs

Cited by 11 publications

References 151 publications

Cisplatin Resistance in Cancer Therapy: Causes and Overcoming Strategies

Cisplatin Resistance in Cancer Therapy: Causes and Overcoming Strategies

Modulating the Activity of the Human Organic Cation Transporter 2 Emerges as a Potential Strategy to Mitigate Unwanted Toxicities Associated with Cisplatin Chemotherapy

(Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand

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