A new study has reported that the proportion of breast cancer stem cells increases in cell cultures as they develop resistance to doxorubicin (Adriamycin) chemotherapy. Cancer stem cells are thought to have nearly unlimited proliferative and self-renewal capabilities and to be highly resistant to chemotherapy.
In the study, the authors tested whether prolonged continuous selection of cells for drug resistance enriches breast cancer cell cultures for cancer stem-like cells, defined as cells that could self-renew, differentiate, invade, and form tumors in mice.
The breast cancer cell lines used in the study included doxorubicin-resistant MCF-7/ADR cells, weakly tumorigenic parental MCF-7 cells, and an MCF-7 subline. Tumors were initiated in mice using grafts of cancer cells in order to examine the ability of the cells to form tumors. In addition, the expression of multidrug resistance genes was evaluated in cancer stem cells and analysis of differentially expressed genes was undertaken.
Doxorubicin-resistant MCF-7/ADR cells were found to express mRNAs from genes that are also found in breast cancer stem cells. MCF-7/ADR cells also were found to be highly invasive and readily formed tumors in mice. Unlike the weakly tumorigenic parental MCF-7 cells, more than 30% of MCF-7/ADR cells could self-renew and differentiate. In other words, they were cancer stem cell-like. These cells also overexpressed a variety of multidrug resistance-linked genes and were significantly more invasive than parental MCF-7 cells. No such enrichment in the stem-cell population was observed in MCF-7/MDR cells. The authors conclude that the cell population with cancer stem cell characteristics increased after prolonged continuous selection for doxorubicin resistance.
Please see our article on foods to eat and avoid while on Adriamycin for more information.
Selected breast cancer studies
Progesterone induces adult mammary stem cell expansion
Joshi PA, Jackson HW, Beristain AG, Di Grappa MA, Mote PA, Clarke CL, et al. Progesterone induces adult mammary stem cell expansion. Nature. Springer Science and Business Media LLC; 2010; 465:803-807 10.1038/nature09091
Sulforaphane, a Dietary Component of Broccoli/Broccoli Sprouts, Inhibits Breast Cancer Stem Cells
Li Y, Zhang T, Korkaya H, Liu S, Lee H, Newman B, et al. Sulforaphane, a Dietary Component of Broccoli/Broccoli Sprouts, Inhibits Breast Cancer Stem Cells. Clinical Cancer Research. American Association for Cancer Research (AACR); 2010; 16:2580-2590 10.1158/1078-0432.ccr-09-2937
Targeting breast stem cells with the cancer preventive compounds curcumin and piperine
Kakarala M, Brenner DE, Korkaya H, Cheng C, Tazi K, Ginestier C, et al. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Research and Treatment. Springer Science and Business Media LLC; 2009; 122:777-785 10.1007/s10549-009-0612-x
Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission
Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K. Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission. Cancer Research. American Association for Cancer Research (AACR); 2009; 69:7507-7511 10.1158/0008-5472.can-09-2994