ArticleProceedings of the National Academy of Sciences of the United States of America2012
Electron transfer-based combination therapy of cisplatin with tetramethyl-p-phenylenediamine for ovarian, cervical, and lung cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 30 citations in OpenAlex.
- New combination chemotherapy of cisplatin with an electron-donating compound for treatment of multiple cancers.Scientific reports · 2021Article
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- Neuroprotective activities of curcumin and quercetin with potential relevance to mitochondrial dysfunction induced by oxaliplatin.Protoplasma · 2016Article
- In Vitro and In Vivo Studies of Non-Platinum-Based Halogenated Compounds as Potent Antitumor Agents for Natural Targeted Chemotherapy of Cancers.EBioMedicine · 2015Article
- Dual targeting of heat shock proteins 90 and 70 promotes cell death and enhances the anticancer effect of chemotherapeutic agents in bladder cancer.Oncology reports · 2014Article
- Antioxidant induces DNA damage, cell death and mutagenicity in human lung and skin normal cells.Scientific reports · 2013Article
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
The platinum-based chemotherapy is the standard treatment for several types of cancer. However, cancer cells often become refractory with time and most patients with serious cancers die of drug resistance. Recently, we have discovered a unique dissociative electron-transfer mechanism of action of cisplatin, the first and most widely used platinum-based anticancer drug. Here, we show that the combination of cisplatin with an exemplary biological electron donor, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), may overcome the resistance of cancer cells to cisplatin. Our steady-state absorption and fluorescence spectroscopic measurements confirm the effective dissociative electron-transfer reaction between TMPD and cisplatin. More significantly, we found that the combination of 100 μM TMPD with cisplatin enhances double-strand breaks of plasmid DNA by a factor of approximately 3.5 and dramatically reduces the viability of cisplatin-sensitive human cervical (HeLa) cancer cells and highly cisplatin-resistant human ovarian (NIH:OVCAR-3) and lung (A549) cancer cells. Furthermore, this combination enhances apoptosis and DNA fragmentation by factors of 2-5 compared with cisplatin alone. These results demonstrate that this combination treatment not only results in a strong synergetic effect, but also makes resistant cancer cells sensitive to cisplatin. Because cisplatin is the cornerstone agent for the treatment of a variety of human cancers (including testicular, ovarian, cervical, bladder, head/neck, and lung cancers), our results show both the potential to improve platinum-based chemotherapy of various human cancers and the promise of femtomedicine as an emerging frontier in advancing cancer therapy.
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