Therapeutic Effect of Clarithromycin on a Transplanted Tumor in Rats

Abstract

The therapeutic antitumor effect of clarithromycin (CAM) was examined with the 13762NF mammary adenocarcinoma and F-344 rat system. When CAM treatment at a dosage of 2 mg/kg of body weight orally for 21 days was commenced after inoculation of the tumor, no significant decrease in death rate was observed, although the loss in body weight was less than that in the untreated group. When tumor-bearing (TB) rats were treated with CAM in combination with carboplatin or cyclophosphamide, a significant decrease in the death rate was obtained, although neither treatment alone proved to be effective. A beneficial effect was also observed when CAM treatment was combined with surgical treatment. CAM showed no direct cytotoxicity to this tumor in vitro according to the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Spleen cells obtained from TB rats receiving CAM treatment showed a stronger tumor-neutralizing activity than those from rats which had not received CAM treatment (Winn assay). Enhanced induction of cytotoxic cells to allogeneic tumor was also observed in rats immunized with allogeneic tumor cells together with CAM treatment (51Cr release assay). The 13762NF tumor produces transforming growth factor-β (TGF-β), tumor necrosis factor alpha, and matrix metalloproteinase-9, and treatment of tumor cells with CAM in vitro for 24 h significantly inhibited the expression of the genes coding for these proteins (reverse transcription-PCR). Levels of expression of the TGF-β and interleukin-6 genes of spleen cells obtained from CAM-treated TB rats were both significantly lower than those of spleen cells from CAM-untreated TB rats. This study suggests that CAM has biological response modifier activities resulting in a beneficial therapeutic antitumor effect and might be useful for the treatment of human cancers.

Anti‐inflammatory and immunomodulating effects of clarithromycin in patients with cystic fibrosis lung disease

“…Thus, it has been demonstrated that only spleen cells obtained from rats that have been immunized by allogeneic tumor cells followed by clarithromycin treatment showed a detectable cytotoxicity to the tumor cells. 30 These data and the fact that macrolide prescription in DPB patients is not accompanied by an increase in P. aeruginosa colonization 14 do not support an inference that long-term administration of these drugs results in imunosuppression.…”

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or “Immuno-Fairy Tales”?

“…Limited trials have been conducted in cystic fibrosis, but preliminary results with azithromycin argue for more clinical investigations (160). Other clinical developments of macrolides outside their antibacterial effects concern their potential benefit in cancer, an effect demonstrated in animal models (336) and patients with lung cancer (254). The mechanisms underlying the antitumoral and anti-inflammatory activity of macrolides are no doubt multiple: studies done ex vivo and in animal models have demonstrated a modulation of neutrophil functions and proinflammatory cytokine production (200).…”

Macrolide antibiotics and the airway: antibiotic or non-antibiotic effects?

“…In ex vivo models, they also block invasiveness of cancer cells, including lung cancer cells [129,130]. Macrolides attenuate the release of TGF-b, the prototypical profibrotic cytokine and inducer of epithelial mesenchymal transition [131]. Macrolides also appear capable of suppressing both the release of and actions of matrix metalloproteinase [111,132].…”