Abstract
To determine if there is any synergistic antitumor effect of ultrasound (US) in the presence of new quinolone (NQ) antibiotics, 0.2 mM solutions of lomefloxacin hydrochloride (LFLX), sparfloxacin (SPFX), ciprofloxacin hydrochloride (CPFX), and gatifloxacin hydrate (GFLX) were tested as sonodynamic agents against sarcoma 180 cells in vitro. After US irradiation at 2 W/cm2 for 30 and 60 s, the survival rates of tumor cells in the presence of NQ antibiotics were significantly lower than those in their absence (P<0.001). In May‐Giemsa smears, most of the tumor cells remained intact in the control group. However, in the 0.2 mM SPFX group, the tumor cells were mostly fragmented. The synergistic antitumor effect of SPFX was dose‐dependent. Furthermore, when D‐mannitol was used with SPFX, the survival rate of tumor cells after irradiation was comparable with that when SPFX alone was applied, but when L‐histidine was used concurrently, the survival rate of tumor cells was significantly higher than that when SPFX alone was applied. These findings suggest that NQ antibiotics would exhibit useful antitumor activity under US irradiation, and that generation of singlet oxygen is involved in the process of cell damage.
References
- 1. Abe H, Kuroki M, Tachibana K, Li T, Awathi A, Ueno A, Matsumoto H, Imakiire T, Yamauchi Y, Yamada H, Ariyoshi A, Kuroki M. Targeted sonodynamic therapy of cancer using a photosensitizer conjugated with antibody against carcinoembryonic antigen. Anticancer Res 2002; 22; 1575–80. [PubMed] [Google Scholar]
- 2. Okada K, Itoi E, Miyakoshi N, Nakajima M, Suzuki T, Nishida J. Enhanced antitumor effect of ultrasound in the presence of piroxicam in a mouse air pouch model. Jpn J Cancer Res 2002; 93: 216–22. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Suzuki T, Kamada S, Yoshida Y, Unno K. A study of sonodynamic‐antitumor effect on novel sonodynamic compounds under ultrasound. Heterocycles 1994; 38: 1209–11. [Google Scholar]
- 4. Yumita N, Nishigaki R, Umemura K, Umemura S. Hematoporphyrin as a sensitizer of cell‐damaging effect of ultrasound. Jpn J Cancer Res 1989; 80: 219–22. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Yumita N, Nishigaki R, Umemura R, Umemura S. Synergistic effect of ultrasound and hematoporphyrin on sarcoma 180. Jpn J Cancer Res 1990; 81: 304–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Dougherty TJ, Kaufman JE, Goldfarb A, Weishaupt KR, Boyle D, Mittleman A. Photoradiation therapy for treatment of malignant tumors. Cancer Res 1978; 38: 2628–35. [PubMed] [Google Scholar]
- 7. Jin ZH, Miyoshi N, Ishiguro K, Umemura S, Kawabata K, Yumita N, Sakata I, Takaoka K, Udagawa T, Nakajima S, Tajiri H, Ueda K, Fukuda M, Kumakiri M. Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice. J Dermatol 2000; 27: 294–306. [DOI] [PubMed] [Google Scholar]
- 8. Sakusabe N, Okada K, Sato K, Kamada S, Yoshida Y, Suzuki T. Enhanced sonodynamic antitumor effect of ultrasound in the presence of nonsteroidal anti‐inflammatory drugs. Jpn J Cancer Res 1999; 90: 1146–51. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Gelber RH, Iranmansh A, Murray L, Siu P, Tsang M. Activities of various quinolone antibiotics against Mycobacterium leprae in infected mice. Antimicrob Agents Chemother 1992; 36: 2544–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Gomer CJ, Jester JV, Razum NJ, Szirth BC, Murphree AL. Photodynamic therapy of intraocular tumors examination of hematoporphyrin derivative distribution and long‐term damage in rabbit ocular tissue. Cancer Res 1985; 45: 3718–25. [PubMed] [Google Scholar]
- 11. Hohnson JH, Cooper MA, Andres JM, Wise R. Pharmacokinetics and inflammatory fluid penetration of sparfloxacin. Antimicrob Agents Chemother 1992; 36: 2444–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J 1996; 10: 709–20. [DOI] [PubMed] [Google Scholar]
- 13. Miyoshi N, Misik V, Riesz P. Sonodynamic toxicity of gallium‐porphyrin analogue ATX‐70 in human leukemia cells. Radial Res 1997; 148: 43–7. [PubMed] [Google Scholar]
- 14. Umemura S, Yumita N, Nishigaki R. Enhancement of ultrasonically induced cell damage by a gallium‐porphyrin complex, ATX‐70. Jpn J Cancer Res 1993; 84: 1582–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Sasaki K, Yumita N, Nishigaki R, Umemura R. Antitumor effect sonodynamically induced by focused ultrasound in combination with Ga‐porphyrin complex. Jpn J Cancer Res 1998; 89: 452–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Chu DT, Hallas R, Clement JJ, Alder J, McDonald E, Plattner JJ. Synthesis and antitumour activities of quinolone antineoplastic agents. Drugs Exp Clin Res 1992; 18: 275–82. [PubMed] [Google Scholar]
- 17. Chu DT, Hallas R, Tanaka SK, Alder J, Balli D, Plattner JJ. Synthesis and antitumor activities of tetracyclic quinolone antineoplastic agents. Drugs Exp Clin Res 1994; 20: 177–83. [PubMed] [Google Scholar]
- 18. Yumita N, Nishigaki R, Umemura K, Morse PD, Swartz HM, Cain CA, Umemura S. Sonochemical activation of hematoporphyrin: an ESR study. Radial Res 1994; 138: 171–6. [PubMed] [Google Scholar]
- 19. Sasaki K, Yumita N, Nishigaki R, Sakata I, Nakajima S. Pharmacokinetic study of a gallium‐porphyrin photo‐ and sono‐sensitizer, ATX‐70, in tumor‐bear mice. Jpn J Cancer Res 2001; 92: 989–95. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Rosen JE, Prahalas AK, Schluter G, Chen D, Williams GM. Quinolone antibiotic photodynamic production of 8–0X0–7, 8‐dihydro‐2‐deoxyguanosine in cultured liver epithelial cells. Photochem Photobiol 1997; 65: 990–6. [DOI] [PubMed] [Google Scholar]
- 21. Hourigan J, Hourigan AF, Kells AF, Schwartz HS. In vitro photodynamic therapy of musculoskeletal neoplasms. J Orthop Res 1993; 11: 633–7. [DOI] [PubMed] [Google Scholar]