Improved photochemotherapy of malignant cells with daunomycin and the KTP laser

Paiva, Marcos B.; Saxton, Romaine E.; Graeber, Ines P.; Jongewaard, N.; Eshraghi, Adrien A.; Suh, Michael; Paek, Woo H.; Castro, Dan J.

doi:10.1002/(sici)1096-9101(1998)23:1<33::aid-lsm5>3.0.co;2-x

Cited by 13 publications

(12 citation statements)

References 24 publications

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“…Hence, laser chemotherapy explores two distinct mechanism of antitumor action: ( 1-) direct toxic effect, and ( 2-) additional photochemical and/or photo thermal toxicity (Bednarski, 2007;Crescenzi et al, 2004;Eshraghi et al, 1997;Mackay et al, 2007). These drugs may be injected intravenously at concentrations lower than normal chemotherapeutic levels, or at higher intratumor doses reducing systemic toxicity while enhancing local tumoricidal effects by laser photoactivation in situ (Nahabedian et al, 1988;Paiva et al, 1998c). Other anthracyclines have also been identified that have greater photosensitization potential than daunomyucin (Diwu and Lown, 1994).…”

Section: Photo-chemical and Photo-thermal Activation Of Anti-cancer Dcontrasting

confidence: 41%

Laser Photo Chemotherapy: An Alternative Treatment for Cancer

Paiva¹,

Palumbo²,

Greggio³

et al. 2011

Current Cancer Treatment - Novel Beyond Conventional Approaches

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Section: Photo-chemical and Photo-thermal Activation Of Anti-cancer Dcontrasting

confidence: 41%

Laser Photo Chemotherapy: An Alternative Treatment for Cancer

Paiva¹,

Palumbo²,

Greggio³

et al. 2011

Current Cancer Treatment - Novel Beyond Conventional Approaches

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“…In living cells, previous studies have shown that DM cytotoxicity is significantly enhanced by laser photoactivation (7,8). However, the cause of the enhancement was not clear.…”

Section: Resultsmentioning

confidence: 99%

“…1). It is also known that the cytotoxicity of DM is enhanced by photoactivation (7,8). The understanding of the recognition process and drug action requires not only the important information about static molecular structures, but also knowledge of the elementary steps of dynamics.…”

mentioning

confidence: 99%

The anticancer drug–DNA complex: Femtosecond primary dynamics for anthracycline antibiotics function

Wan

Becker

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The anthracycline-DNA complex, which is a potent agent for cancer chemotherapy, has a unique intercalating molecular structure with preference to the GC bases of DNA, as shown by Rich's group in studies of single-crystal x-ray diffraction. Understanding cytotoxicity and its photoenhancement requires the unraveling of the dynamics under the solution-phase, physiological condition. Here we report our first study of the primary processes of drug function. In a series of experiments involving the drug (daunomycin and adriamycin) in water, the drug-DNA complexes, the complexes with the four nucleotides (dGTP, dATP, dCTP, and dTTP), and the drug-apo riboflavin-binding protein, we show the direct involvement of molecular oxygen and DNA base-drug chargeseparation-the rates for the reduction of the drug and dioxygen indicate the crucial role of drug/base/O2 in the efficient and catalytic redox cycling. These dynamical steps, and the subsequent reactions of the superoxide product(s), can account for the photoenhanced function of the drug in cells, and potentially for the cell death. D rug molecules that target a particular DNA sequence have shown selectivity to inhibit or modulate gene expression and are valuable for a variety of chemotherapeutic strategies (1, 2). Daunomycin (DM), one of the anthracycline antibiotics, is among the most effective drugs for cancer chemotherapy. Previous studies of single-crystal molecular structures (3, 4) and solution-phase binding thermodynamics and kinetics (5, 6) have demonstrated that DM molecules have preference for the GC bases of DNA and intercalate into GC base pairs (Fig. 1). It is also known that the cytotoxicity of DM is enhanced by photoactivation (7,8). The understanding of the recognition process and drug action requires not only the important information about static molecular structures, but also knowledge of the elementary steps of dynamics. For a rational design of reactivity (9), unraveling the dynamics under physiological conditions of hydration and oxygenation is essential to the function.In this contribution, we report direct observation of the primary processes involved in DM and adriamycin (AM) drug action. It is found that the selective recognition of GC enhances charge separation with the net transfer of electron to the drug. Furthermore, we observe a striking effect of dioxygen on the drug-dGTP nucleotide in water-the presence of O 2 depletes the drug radical population, leading to the formation of superoxide anion radicals (see below), whereas its absence leads to charge recombination to reform the initial state. Because these reactions were found to be ultrafast in nature, all subsequent reactions involving dioxygen occur as a result of charge separation. These processes can account for the photoenhancement of the drug action in cells, cytotoxicity, and potentially as precursors for the cell death. We discuss the relationship of this effect of enhanced cell damage to the less efficient thermal reaction involving a similar transition state. We also report resul...

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“…Many laboratories [9][10][11] demonstrated that low-power laser irradiation (LPLI) promotes the growth of MSCs. There are some studies suggesting that combination of laser and chemotherapy can be useful in the treatment of malignant diseases, because laser therapy enhances the cytotoxicity of the chemotherapeutic drug [12,13]. On the other hand, Wong and Wilder-Smith [14] used laser irradiation for prophylaxis before the chemotherapy and they detected significant reduction of the severity and the incidence of oral mucositis.…”

Section: Introductionmentioning

confidence: 99%