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Preparation, In Vivo Administration, Dose-Limiting Toxicities, and Antineoplastic Activity of Cytochalasin B.

Trendowski M, Zoino JN, Christen TD, Acquafondata C, Fondy TP - Transl Oncol (2015)

Bottom Line: We also examine the effects of cytochalasin B against several other murine neoplastic cell lines (Lewis lung, LA4, B16F10, and M5076).Finally, we examine a potential mechanism of the antimetastatic activity of cytochalasin B by observing the effects of the agent on the secretion of N-acetylglucosaminidase (GlcNACase) by B16BL6 and B16F10 murine melanomas in vitro.These effects were comparable to intraperitoneally administered doxorubicin. 4) Low concentrations of cytochalasin B inhibit the secretion of GlcNACase, indicating that cytochalasin B may inhibit metastatic progression by mechanisms not directly associated with its influence on cell adhesion and motility.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY 13244, USA. Electronic address: mrtrendo@syr.edu.

No MeSH data available.


Related in: MedlinePlus

Effects of cytochalasin B administered five times as a 5-mg/kg i.v. bolus dose and doxorubicin administered once or twice as a 5-mg/kg i.p. dose on M109 murine lung carcinoma. (A) Effects on the long-term growth of established M109c i.d. tumor nodules. Cytochalasin B was administered on days 1 to 5 following tumor challenge. Doxorubicin was administered on day 1 and on days 1 and 3 following tumor challenge. There were 16 mice in the CB-treated cohort, 10 mice in both doxorubicin-treated groups, and 10 mice in the cohort that received only the vehicle. The CB-treated group was significantly different from the control and doxorubicin-treated groups; P < .01 for between-subject effects, P < .05 for time versus group interactions. Bars reflect SEM of the treatment groups. (B) Effects of cytochalasin B administered as a 5-mg/kg i.v. bolus dose and doxorubicin as a 5-mg/kg i.p. dose on the survival of Balb/c mice challenged with M109c lung carcinoma. Survival of mice treated with cytochalasin B (n = 16) was significantly different from that of mice receiving the doxorubicin regimens (n = 10 for both groups) or only the vehicle (n = 10); P < .05, as assessed by a Cox-Mantel test. (C) In vivo activity of cytochalasin B administered as a 5-mg/kg i.v. bolus dose or doxorubicin administered as a 5-mg/kg i.p. dose against the metastatic spread of M109c lung carcinoma. Size of all treatment groups is indicated in the figure. The lungs were the only tissue that contained substantial metastases. Bars reflect SEM of each treatment group.
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f0015: Effects of cytochalasin B administered five times as a 5-mg/kg i.v. bolus dose and doxorubicin administered once or twice as a 5-mg/kg i.p. dose on M109 murine lung carcinoma. (A) Effects on the long-term growth of established M109c i.d. tumor nodules. Cytochalasin B was administered on days 1 to 5 following tumor challenge. Doxorubicin was administered on day 1 and on days 1 and 3 following tumor challenge. There were 16 mice in the CB-treated cohort, 10 mice in both doxorubicin-treated groups, and 10 mice in the cohort that received only the vehicle. The CB-treated group was significantly different from the control and doxorubicin-treated groups; P < .01 for between-subject effects, P < .05 for time versus group interactions. Bars reflect SEM of the treatment groups. (B) Effects of cytochalasin B administered as a 5-mg/kg i.v. bolus dose and doxorubicin as a 5-mg/kg i.p. dose on the survival of Balb/c mice challenged with M109c lung carcinoma. Survival of mice treated with cytochalasin B (n = 16) was significantly different from that of mice receiving the doxorubicin regimens (n = 10 for both groups) or only the vehicle (n = 10); P < .05, as assessed by a Cox-Mantel test. (C) In vivo activity of cytochalasin B administered as a 5-mg/kg i.v. bolus dose or doxorubicin administered as a 5-mg/kg i.p. dose against the metastatic spread of M109c lung carcinoma. Size of all treatment groups is indicated in the figure. The lungs were the only tissue that contained substantial metastases. Bars reflect SEM of each treatment group.

Mentions: Administration of cytochalasin B as a 5-mg/kg/day i.v. bolus dose on days 1 to 5 to Balb/c mice challenged i.d. with 2 × 105 M109c cells appeared to markedly perturb tumor growth (Figure 3A). At 30 days postchallenge, cytochalasin B–treated mice had a mean tumor volume of 0.53 cm3 (standard error of the mean; SEM = 0.04), whereas mice treated with the vehicle had a mean tumor volume of 0.9 cm3 (SEM = 0.034). Doxorubicin administered as a 5-mg/kg i.p. dose once or twice had a notable antitumor effect, but it was not as pronounced as cytochalasin B (Figure 3A). These effects on tumor growth appear to be supported by the long-term survival potentiated by the 5-mg/kg/day i.v. bolus cytochalasin B treatment protocol (Figure 3B). There was a 50% survival rate at least up to day 53 for mice challenged with an i.d. tumor nodule in the cohort treated five times with 5-mg/kg i.v. bolus cytochalasin B (n = 16). This is a highly significant prolonging of life expectancy, as all mice treated with the vehicle were dead by day 42 (n = 10). By contrast, mice treated once with 5 mg/kg i.p. doxorubicin were all dead by day 50 (n = 10), and only 1 in 10 mice treated twice with 5 mg/kg i.p. doxorubicin was alive after 53 days. These data are further supported by a Cox-Mantel test that indicated a P < .05 for each treatment cohort.


Preparation, In Vivo Administration, Dose-Limiting Toxicities, and Antineoplastic Activity of Cytochalasin B.

Trendowski M, Zoino JN, Christen TD, Acquafondata C, Fondy TP - Transl Oncol (2015)

Effects of cytochalasin B administered five times as a 5-mg/kg i.v. bolus dose and doxorubicin administered once or twice as a 5-mg/kg i.p. dose on M109 murine lung carcinoma. (A) Effects on the long-term growth of established M109c i.d. tumor nodules. Cytochalasin B was administered on days 1 to 5 following tumor challenge. Doxorubicin was administered on day 1 and on days 1 and 3 following tumor challenge. There were 16 mice in the CB-treated cohort, 10 mice in both doxorubicin-treated groups, and 10 mice in the cohort that received only the vehicle. The CB-treated group was significantly different from the control and doxorubicin-treated groups; P < .01 for between-subject effects, P < .05 for time versus group interactions. Bars reflect SEM of the treatment groups. (B) Effects of cytochalasin B administered as a 5-mg/kg i.v. bolus dose and doxorubicin as a 5-mg/kg i.p. dose on the survival of Balb/c mice challenged with M109c lung carcinoma. Survival of mice treated with cytochalasin B (n = 16) was significantly different from that of mice receiving the doxorubicin regimens (n = 10 for both groups) or only the vehicle (n = 10); P < .05, as assessed by a Cox-Mantel test. (C) In vivo activity of cytochalasin B administered as a 5-mg/kg i.v. bolus dose or doxorubicin administered as a 5-mg/kg i.p. dose against the metastatic spread of M109c lung carcinoma. Size of all treatment groups is indicated in the figure. The lungs were the only tissue that contained substantial metastases. Bars reflect SEM of each treatment group.
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Related In: Results  -  Collection

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f0015: Effects of cytochalasin B administered five times as a 5-mg/kg i.v. bolus dose and doxorubicin administered once or twice as a 5-mg/kg i.p. dose on M109 murine lung carcinoma. (A) Effects on the long-term growth of established M109c i.d. tumor nodules. Cytochalasin B was administered on days 1 to 5 following tumor challenge. Doxorubicin was administered on day 1 and on days 1 and 3 following tumor challenge. There were 16 mice in the CB-treated cohort, 10 mice in both doxorubicin-treated groups, and 10 mice in the cohort that received only the vehicle. The CB-treated group was significantly different from the control and doxorubicin-treated groups; P < .01 for between-subject effects, P < .05 for time versus group interactions. Bars reflect SEM of the treatment groups. (B) Effects of cytochalasin B administered as a 5-mg/kg i.v. bolus dose and doxorubicin as a 5-mg/kg i.p. dose on the survival of Balb/c mice challenged with M109c lung carcinoma. Survival of mice treated with cytochalasin B (n = 16) was significantly different from that of mice receiving the doxorubicin regimens (n = 10 for both groups) or only the vehicle (n = 10); P < .05, as assessed by a Cox-Mantel test. (C) In vivo activity of cytochalasin B administered as a 5-mg/kg i.v. bolus dose or doxorubicin administered as a 5-mg/kg i.p. dose against the metastatic spread of M109c lung carcinoma. Size of all treatment groups is indicated in the figure. The lungs were the only tissue that contained substantial metastases. Bars reflect SEM of each treatment group.
Mentions: Administration of cytochalasin B as a 5-mg/kg/day i.v. bolus dose on days 1 to 5 to Balb/c mice challenged i.d. with 2 × 105 M109c cells appeared to markedly perturb tumor growth (Figure 3A). At 30 days postchallenge, cytochalasin B–treated mice had a mean tumor volume of 0.53 cm3 (standard error of the mean; SEM = 0.04), whereas mice treated with the vehicle had a mean tumor volume of 0.9 cm3 (SEM = 0.034). Doxorubicin administered as a 5-mg/kg i.p. dose once or twice had a notable antitumor effect, but it was not as pronounced as cytochalasin B (Figure 3A). These effects on tumor growth appear to be supported by the long-term survival potentiated by the 5-mg/kg/day i.v. bolus cytochalasin B treatment protocol (Figure 3B). There was a 50% survival rate at least up to day 53 for mice challenged with an i.d. tumor nodule in the cohort treated five times with 5-mg/kg i.v. bolus cytochalasin B (n = 16). This is a highly significant prolonging of life expectancy, as all mice treated with the vehicle were dead by day 42 (n = 10). By contrast, mice treated once with 5 mg/kg i.p. doxorubicin were all dead by day 50 (n = 10), and only 1 in 10 mice treated twice with 5 mg/kg i.p. doxorubicin was alive after 53 days. These data are further supported by a Cox-Mantel test that indicated a P < .05 for each treatment cohort.

Bottom Line: We also examine the effects of cytochalasin B against several other murine neoplastic cell lines (Lewis lung, LA4, B16F10, and M5076).Finally, we examine a potential mechanism of the antimetastatic activity of cytochalasin B by observing the effects of the agent on the secretion of N-acetylglucosaminidase (GlcNACase) by B16BL6 and B16F10 murine melanomas in vitro.These effects were comparable to intraperitoneally administered doxorubicin. 4) Low concentrations of cytochalasin B inhibit the secretion of GlcNACase, indicating that cytochalasin B may inhibit metastatic progression by mechanisms not directly associated with its influence on cell adhesion and motility.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY 13244, USA. Electronic address: mrtrendo@syr.edu.

No MeSH data available.


Related in: MedlinePlus