In vitro toxicity to breast cancer cells of microsphere-delivered mitomycin C and its combination with doxorubicin

Richard Y. Cheung; Andrew M. Rauth; Patrick T. Ronaldson; Reina Bendayan; Xiao Yu Wu

doi:10.1016/j.ejpb.2005.09.011

In vitro toxicity to breast cancer cells of microsphere-delivered mitomycin C and its combination with doxorubicin

Richard Y. Cheung, Andrew M. Rauth, Patrick T. Ronaldson, Reina Bendayan, Xiao Yu Wu

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

To better understand and design microsphere systems for the locoregional delivery of anticancer drug combinations to solid tumors, (1) the cytotoxicity of microsphere-delivered mitomycin C (MMC) was evaluated and (2) various schedules of MMC and doxorubicin (Dox) were tested for their toxicity in vitro towards a murine breast cancer cell-line, EMT6. To accomplish the former MMC was loaded onto oxidized sulfopropyl dextran microspheres, released in a pH 7.4 buffer solution and tested for its potency against EMT6 cells versus a standard MMC solution. For the latter EMT6 cells were exposed to MMC or Dox as single agents or together using various drug concentrations and schedules. The efficacy of the treatments was measured using a clonogenic assay. MMC released from the microspheres showed similar activity against EMT6 cells to freshly prepared MMC solutions. Greater-than-additive toxicity was observed when MMC was given either simultaneously or after Dox exposure. In contrast, administration of MMC before Dox exposure resulted in toxicity that ranged from additive to sub-additive; this reduced toxicity was mainly due to increasing cell density arising from the design of the assay. These results help explain our previous in vivo investigations using microsphere-delivered combinations of the same agents in EMT6 solid tumors.

Original language	English (US)
Pages (from-to)	321-331
Number of pages	11
Journal	European Journal of Pharmaceutics and Biopharmaceutics
Volume	62
Issue number	3
DOIs	https://doi.org/10.1016/j.ejpb.2005.09.011
State	Published - Apr 2006

Keywords

Anticancer drug combinations
Breast cancer cells
Doxorubicin
Microspheres
Mitomycin C

ASJC Scopus subject areas

Biotechnology
Pharmaceutical Science

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10.1016/j.ejpb.2005.09.011

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title = "In vitro toxicity to breast cancer cells of microsphere-delivered mitomycin C and its combination with doxorubicin",

abstract = "To better understand and design microsphere systems for the locoregional delivery of anticancer drug combinations to solid tumors, (1) the cytotoxicity of microsphere-delivered mitomycin C (MMC) was evaluated and (2) various schedules of MMC and doxorubicin (Dox) were tested for their toxicity in vitro towards a murine breast cancer cell-line, EMT6. To accomplish the former MMC was loaded onto oxidized sulfopropyl dextran microspheres, released in a pH 7.4 buffer solution and tested for its potency against EMT6 cells versus a standard MMC solution. For the latter EMT6 cells were exposed to MMC or Dox as single agents or together using various drug concentrations and schedules. The efficacy of the treatments was measured using a clonogenic assay. MMC released from the microspheres showed similar activity against EMT6 cells to freshly prepared MMC solutions. Greater-than-additive toxicity was observed when MMC was given either simultaneously or after Dox exposure. In contrast, administration of MMC before Dox exposure resulted in toxicity that ranged from additive to sub-additive; this reduced toxicity was mainly due to increasing cell density arising from the design of the assay. These results help explain our previous in vivo investigations using microsphere-delivered combinations of the same agents in EMT6 solid tumors.",

keywords = "Anticancer drug combinations, Breast cancer cells, Doxorubicin, Microspheres, Mitomycin C",

author = "Cheung, {Richard Y.} and Rauth, {Andrew M.} and Ronaldson, {Patrick T.} and Reina Bendayan and Wu, {Xiao Yu}",

note = "Funding Information: This work is supported by the Canadian Institutes of Health Research (MOP53165, MOP63005). The authors would like to thank Dr I.F. Tannock for providing the cells and Ms G. Lim for statistical consultation. The Ontario Graduate Scholarship, University of Toronto Open Fellowship, Ben Cohen Bursary, and Pharmacy Alumni Graduate Student Award to RC are also gratefully acknowledged.",

year = "2006",

month = apr,

doi = "10.1016/j.ejpb.2005.09.011",

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AU - Cheung, Richard Y.

AU - Rauth, Andrew M.

AU - Ronaldson, Patrick T.

AU - Bendayan, Reina

AU - Wu, Xiao Yu

N1 - Funding Information: This work is supported by the Canadian Institutes of Health Research (MOP53165, MOP63005). The authors would like to thank Dr I.F. Tannock for providing the cells and Ms G. Lim for statistical consultation. The Ontario Graduate Scholarship, University of Toronto Open Fellowship, Ben Cohen Bursary, and Pharmacy Alumni Graduate Student Award to RC are also gratefully acknowledged.

PY - 2006/4

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N2 - To better understand and design microsphere systems for the locoregional delivery of anticancer drug combinations to solid tumors, (1) the cytotoxicity of microsphere-delivered mitomycin C (MMC) was evaluated and (2) various schedules of MMC and doxorubicin (Dox) were tested for their toxicity in vitro towards a murine breast cancer cell-line, EMT6. To accomplish the former MMC was loaded onto oxidized sulfopropyl dextran microspheres, released in a pH 7.4 buffer solution and tested for its potency against EMT6 cells versus a standard MMC solution. For the latter EMT6 cells were exposed to MMC or Dox as single agents or together using various drug concentrations and schedules. The efficacy of the treatments was measured using a clonogenic assay. MMC released from the microspheres showed similar activity against EMT6 cells to freshly prepared MMC solutions. Greater-than-additive toxicity was observed when MMC was given either simultaneously or after Dox exposure. In contrast, administration of MMC before Dox exposure resulted in toxicity that ranged from additive to sub-additive; this reduced toxicity was mainly due to increasing cell density arising from the design of the assay. These results help explain our previous in vivo investigations using microsphere-delivered combinations of the same agents in EMT6 solid tumors.

AB - To better understand and design microsphere systems for the locoregional delivery of anticancer drug combinations to solid tumors, (1) the cytotoxicity of microsphere-delivered mitomycin C (MMC) was evaluated and (2) various schedules of MMC and doxorubicin (Dox) were tested for their toxicity in vitro towards a murine breast cancer cell-line, EMT6. To accomplish the former MMC was loaded onto oxidized sulfopropyl dextran microspheres, released in a pH 7.4 buffer solution and tested for its potency against EMT6 cells versus a standard MMC solution. For the latter EMT6 cells were exposed to MMC or Dox as single agents or together using various drug concentrations and schedules. The efficacy of the treatments was measured using a clonogenic assay. MMC released from the microspheres showed similar activity against EMT6 cells to freshly prepared MMC solutions. Greater-than-additive toxicity was observed when MMC was given either simultaneously or after Dox exposure. In contrast, administration of MMC before Dox exposure resulted in toxicity that ranged from additive to sub-additive; this reduced toxicity was mainly due to increasing cell density arising from the design of the assay. These results help explain our previous in vivo investigations using microsphere-delivered combinations of the same agents in EMT6 solid tumors.

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In vitro toxicity to breast cancer cells of microsphere-delivered mitomycin C and its combination with doxorubicin

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