Description

Product Description

Cisplatin, chemically known as cis-diamminedichloroplatinum(II), is a coordination complex that revolutionized the study of DNA-damaging agents and platinum-based chemotherapeutics. Structurally, it consists of a central platinum atom coordinated to two chloride ions and two ammonia ligands in a cis configuration. This unique geometry is critical to its ability to form covalent bonds with nucleophilic sites on DNA, particularly the N7 positions of guanine and adenine residues.

As one of the earliest discovered platinum compounds with potent cytotoxic activity, cisplatin has been extensively used as a model compound for understanding DNA repair mechanisms, apoptosis pathways, and cellular stress responses. In biochemical research, cisplatin serves as a benchmark for exploring the role of DNA damage in cancer cell death, oxidative stress, and cell-cycle arrest.

When introduced into an aqueous environment, the chloride ligands of cisplatin undergo a slow hydrolysis process to form reactive aqua complexes. These aquated species are electrophilic and capable of binding to nucleophilic DNA sites, resulting in the formation of DNA-platinum adducts. The most predominant lesion formed is the 1,2-intrastrand crosslink between adjacent guanine bases, which bends and unwinds the DNA double helix. This distortion disrupts replication and transcription, leading to replication fork stalling and activation of DNA damage response (DDR) pathways.

Cisplatin-induced DNA lesions are recognized by high-mobility group (HMG) proteins and other DNA-binding factors, triggering a cascade of molecular events that culminate in cell-cycle arrest and programmed cell death. The extent of DNA adduct formation, as well as the efficiency of DNA repair by nucleotide excision repair (NER) enzymes, determines cellular sensitivity to platinum compounds. Therefore, cisplatin remains an essential research reagent in the study of DNA repair, apoptosis, and chemoresistance mechanisms.

In addition to its direct DNA-binding effects, cisplatin has been found to generate reactive oxygen species (ROS), which amplify cellular damage through lipid peroxidation, mitochondrial dysfunction, and oxidative modification of proteins. These secondary pathways provide valuable models for oxidative stress studies and for understanding redox biology in the context of cytotoxicity.

Researchers also use cisplatin in comparative studies of platinum analogs, such as carboplatin, oxaliplatin, and nedaplatin, to analyze structure-activity relationships. Such comparative models provide crucial insights into the pharmacodynamics and cellular transport mechanisms of platinum drugs.

In vitro, cisplatin’s biological effects are highly concentration- and time-dependent. Low doses primarily cause reversible DNA lesions and mild activation of repair pathways, whereas high doses lead to irreversible DNA crosslinks, cell-cycle arrest, and apoptosis. For this reason, cisplatin is frequently used in cell culture assays, comet assays, and DNA-binding kinetics studies.

Due to its wide-ranging applications in cancer biology, DNA chemistry, and pharmacology, cisplatin continues to serve as a cornerstone compound for molecular oncology and cytotoxic mechanism research.

Product Specifications

Mechanism of Action

Cisplatin exerts its primary biochemical activity through covalent binding to DNA, leading to the formation of intra- and inter-strand crosslinks. The core mechanism involves the substitution of chloride ligands with water molecules under physiological conditions, generating aquated species that are highly reactive toward nucleophilic DNA sites.

1. DNA Binding and Crosslink Formation

Cisplatin’s electrophilic platinum center preferentially binds to the N7 atom of guanine residues. The most abundant adducts are 1,2-intrastrand d(GpG) and d(ApG) crosslinks, which induce a significant bend in the DNA double helix (up to 30°). This distortion hinders transcription and replication processes, activating DNA damage checkpoints and repair mechanisms.

2. Induction of Apoptosis

DNA damage caused by cisplatin triggers a cascade of intracellular responses, including p53 activation, upregulation of pro-apoptotic proteins (Bax, PUMA), and mitochondrial cytochrome c release. These events lead to caspase activation and programmed cell death. The mitochondrial pathway of apoptosis is particularly important in cisplatin-induced cytotoxicity, as ROS accumulation further amplifies mitochondrial damage.

3. Oxidative Stress and Mitochondrial Dysfunction

Cisplatin indirectly promotes ROS production through interactions with mitochondrial complexes I and III. The resulting oxidative stress damages lipids, proteins, and nucleic acids, contributing to secondary cytotoxic effects. Manganese superoxide dismutase (MnSOD) and glutathione peroxidase play crucial protective roles in modulating these effects, making cisplatin a useful reagent for oxidative stress and antioxidant research.

4. Signal Transduction Modulation

Cisplatin activates several key signal transduction pathways, including MAPK, JNK, and ERK cascades, leading to transcriptional regulation of apoptosis-related genes. It also influences the PI3K/Akt pathway, which contributes to cell survival and chemoresistance. These signaling networks make cisplatin a valuable model compound for studying stress response and drug resistance in cancer cells.

5. Transport and Detoxification

Cisplatin enters cells primarily via passive diffusion and copper transporters (CTR1), while efflux is mediated by ATP7A and ATP7B. Intracellular detoxification occurs through conjugation with glutathione, which forms platinum–glutathione adducts that can be exported by multidrug resistance proteins. Understanding these mechanisms is essential for studying platinum resistance and metallothionein-mediated detoxification pathways.

Side Effects

In research applications, cisplatin exhibits concentration-dependent cytotoxicity. At high levels, it induces apoptosis, necrosis, and DNA fragmentation. Typical cellular effects include mitochondrial swelling, ROS overproduction, and activation of stress kinases.

While cisplatin remains an invaluable research tool, it should be handled with caution. Laboratory studies have shown that prolonged exposure can affect cellular metabolism, disrupt protein folding, and induce oxidative injury in hepatocytes and renal epithelial models.

To ensure reproducible results and laboratory safety, researchers should:

• Use personal protective equipment (PPE) including gloves, masks, and eye protection.

• Prepare fresh solutions immediately before use to minimize hydrolysis.

• Dispose of platinum-containing waste following hazardous material regulations.

Cisplatin is not intended for therapeutic or in vivo use, but only for controlled laboratory and biochemical experiments.

Keywords

Cisplatin, platinum coordination complex, DNA crosslinking agent, apoptosis inducer, oxidative stress research, chemoresistance model, DNA damage pathway, factory chemical supplier, bulk reagent China, high-purity platinum compound

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Disclaimer

All products listed are intended for laboratory research use only and not for human or veterinary use. They are not drugs, medical devices, or diagnostics and should not be administered to humans or animals. Researchers must handle all materials in accordance with institutional biosafety and chemical safety guidelines. The information provided is for scientific reference only and does not imply therapeutic efficacy, safety, or regulatory approval.