Abstract

More patients are
surviving cancer than ever before and this makes co-morbidity factors such as
cardiotoxicity important issues in the quantity and quality of life of cancer
survivors. It is important to be able to assess the cardiotoxic risk of new and
existing cancer therapies. Changes in electrical impedance of cell-covered
electrodes, for example, is one possible method. Alterations in the electrical
impedance occur due to changes in morphology, cell contact, confluency and
contractility which result from toxic effects on cells.  Measurements using electrical impedance are
non-invasive and can be monitored over long periods of time.

 

In this study,
electrical impedance was used to monitor cell regrowth in breast cancer in vitro following chemotherapy treatment. In order to assess the
cardiotoxic potential of this treatment, the
same combination therapy was tested on human stem cell-derived cardiomyocytes
(hSC-CMs). The combination of cyclophosphamide, adriamycin (doxorubicin) and 5-fluorouracil (CAF)
administered for 4 months is a standard treatment for breast cancer patients
and although often initially successful, tumor recurrence after this therapy
remains a major cause of mortality in breast cancer patients. Using a murine
carcinoma cell line (H8N8), we were able to investigate the effect of CAF
treatment in vitro on untreated
cancer cells and on tumor regrowth on H8N8 T3.2 cells previously treated with
the regime. In addition, we tested the CAF treatment and paclitaxel on hSC-CMs.
Paclitaxel caused a concentration and time-dependent reduction in viability of
hSC-CMs as measured by a decrease in base impedance and caused a decrease in
mean beat amplitude indicating an effect on contractility. Doxorubicin caused
cardiotoxicity when present in any combination (alone or with cyclophosphamide
or 5-fluorouracil) whereas cyclophosphamide or 5-Fluorouracil did not affect
cell viability when applied alone or in combination with each other. Doxorubicin also caused a decrease in mean beat amplitude indicating a
change in contractility.

 

In summary, using electrical impedance, acute and
long-term effects of cancer therapy on cell proliferation of tumor cells, and
cardiotoxic effects of chemotherapeutics can be identified. Such in vitro experiments are important to
identify potential novel cancer therapeutics and also to promote cardiovascular
health during cancer therapy.