Clarithromycin is a potent inhibitor of tumor-induced angiogenesis

Ye, Jun; Turuta, Nobuko; Wakamatsu, Kentaro; Hara, Nobuyuki; Hayashi, Shinichiro

doi:10.1007/s004330050068

Cited by 39 publications

(34 citation statements)

References 18 publications

(23 reference statements)

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“…While it appears that the inhibitory effects of clarithromycin and roxithromycin on angiogenesis were not due to the inhibition of ECs and/or tumor cell proliferation, the precise mechanism of how clarithromycin and roxithromycin act on ECs and inhibit tumor angiogenesis in vivo has not been elucidated (Yatsunami et al, 1999a). The concentrations at which clarithromycin and roxithromycin showed antiangiogenic activity in vitro were greater than 10 and 20 mM, respectively (Yatsunami et al, 1997(Yatsunami et al, , 1998, whereas GDA inhibited bFGF-induced EC migration and tube formation at 3 and 10 nM, respectively. Therefore GDA appears to be a more potent antiangiogenic agent than clarithromycin and roxithromycin, although the cells used in the studies were different (BAECs for GDA, HUVECs for clarithromycin and roxithromycin).…”

Section: Discussionmentioning

confidence: 98%

Goniodomin A, an antifungal polyether macrolide, exhibits antiangiogenic activities via inhibition of actin reorganization in endothelial cells

Abé

Inoue

Matsunaga

et al. 2001

Journal Cellular Physiology

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Goniodomin A (GDA) is an antifungal polyether macrolide isolated from the dinoflagellate Goniodoma pseudogoniaulax. Previous studies revealed that GDA profoundly affected cytoskeletal reorganization. We examined the effect of GDA on the angiogenic properties of vascular endothelial cells. GDA itself did not affect proliferation of, migration of, and tube formation in type I collagen gels by, bovine aortic endothelial cells (BAECs). Proliferation of BAECs stimulated by bFGF was not affected by GDA at concentrations of up to 10 nM. However, at similar concentrations, GDA significantly inhibited bFGF-induced migration and tube formation in type I collagen gels by BAECs. Actin reorganization is required for cell migration. GDA caused the perinuclear aggregation of filamentous actin and inhibited stress fiber formation in bFGF- or VEGF-stimulated BAECs and lysophosphatidic acid-stimulated HeLa cells. However, GDA did not affect stress fiber structures already formed through Gbetagamma expression or in constitutively active RhoA mutant HeLa cells. Finally, GDA inhibited forming of vasucular system in a chorioallantoic membrane. Our results indicated that GDA suppressed angiogenic properties of ECs at least in part through the inhibition of actin reorganization and inhibited angiogenesis in vivo.

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Section: Discussionmentioning

confidence: 98%

Goniodomin A, an antifungal polyether macrolide, exhibits antiangiogenic activities via inhibition of actin reorganization in endothelial cells

Abé

Inoue

Matsunaga

et al. 2001

Journal Cellular Physiology

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“…These parameters reflect that this macrolide has a considerable "cleansing" effect at the operative site, leading to a much weaker local inflammatory response and a much better clinical outcome. In addition to the immunomodulatory effects of clarithromycin on surgical trauma, this drug has also been reported to be a potent inhibitor of tumor-induced angiogenesis in a mouse cancer model (35). A clinical study also demonstrated that the drug prolonged survival of patients with unresectable non-small-cell lung cancer by increasing the bioactivity of IL-12 and natural killer cell activity (26).…”

Section: Discussionmentioning

confidence: 99%

Clarithromycin Attenuates Mastectomy-Induced Acute Inflammatory Response

Chow¹,

Yuen

Woo

et al. 2000

Clin Diagn Lab Immunol

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Based on the observation that administration of clarithromycin led to an attenuation of the inflammatory response induced by surgical trauma in a guinea pig model, we investigated the potential beneficial effects of clarithromycin on the local and systemic inflammatory response in patients undergoing mastectomy in an open-label prospective study. During a 16-month period, 54 patients who underwent mastectomy were randomly divided into two groups. In one group, the patients received oral clarithromycin at a dose of 500 mg twice a day, from the day before to 3 days after mastectomy. There was no significant difference in the incidence of antibiotic prophylaxis-related toxicities or postoperative infections between the patients who received clarithromycin and those who did not. Clarithromycin treatment was significantly associated with an attenuation of febrile response, tachycardia, tachypnea, and an increase in monocyte counts (P, <0.0001, <0.01, <0.05, and <0.01, respectively). Clarithromycin also reduced the intensity and duration of postoperative pain (P, <0.05 and <0.005, respectively) and increased the range of motion of the involved shoulder (P < 0.05 for abduction and flexion). We conclude that clarithromycin effectively modulates the acute inflammatory response associated with mastectomy and produces a better clinical outcome.Surgical operations induce major physiological and immunological changes. These changes are activated by various stimuli, such as nociceptive stimulation, tissue injury, tissue ischemia, reperfusion, and hemodynamic disturbances. The clinical response is the result of complex changes, which include dysregulation of T-cell function, changes in the balance of cytokines and counterregulatory hormones, and increased hepatic synthesis of acute-phase reactants. In most patients, the systemic changes are minimal and self-limiting. However, in patients with complicated surgery or major trauma, the response becomes extensive and prolonged, resulting in systemic inflammatory response syndrome (SIRS), which is characterized by increased or suppressed body temperature, increased heart rate, hyperventilation, and an abnormal peripheral leukocyte count (2). Although an inflammatory response is an inevitable and essential part of the repair process and a natural defensive reaction to prevent infections associated with trauma, such undesirable fallout from surgical treatment is associated with significant morbidity and even mortality.The macrolide group of antibiotics is associated with in vitro and in vivo immunomodulating activities (18,(31)(32)(33). Erythromycin, one of the macrolides, has been used extensively for antimicrobial prophylaxis in colorectal surgery (22). Recently, it has also been shown that clarithromycin attenuates the inflammatory response induced by surgical trauma in a guinea pig model (32).Mastectomy is a suitable surgical procedure for the study of the acute inflammatory response to surgery because the extensive dissection causes significant tissue damage and bacterial contam...

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“…For the patients who are diagnosed as SCLC and have mycoplasma infection in tumor cells, a new chemotherapeutic protocol can be formed with the purpose of supporting the treatment and the survival [7,8]. Claritromycin which is potent inhibitor of tumor angiogenesis and proposed in multiple myeloma chemotherapy protocols, can be used in SCLC patients who are positive for mycoplasma infections [9].…”

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confidence: 99%