The authors of the study further affirm these points:
Cancer stem cells pose serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. To add into the misery, very few chemotherapeutic compounds show promise to kill these cells. Several researchers have shown that cancer stem cells are resistant to paclitaxel, doxorubicin, 5-fluorouracil, and platinum drugs [8, 16]. CSCs are thus an almost unreachable population in tumours for chemotherapy. Therefore any compound, that shows promise towards cancer stem cells, is a highly desirable step towards cancer treatment and should be followed up for further development.
The researchers identified a variety of ways by which 6-shagoal targets breast cancer:
- It reduces the expression of CD44/CD24 cancer stem cell surface markers in breast cancer spheroids (3-dimensional cultures of cells modeling stem cell like cancer)
- It significantly affects the cell cycle, resulting in increased cancer cell death
- It induces programmed cell death primarily through the induction of autophagy, with apoptosis a secondary inducer
- It inhibits breast cancer spheroid formation by altering Notch signaling pathway through γ-secretase inhibition.
- It exhibits cytotoxicity (cell killing properties) against monolayer (1-dimensional cancer model) and spheroid cells (3-dimensional cancer model)
It was in evaluating the last mode of 6-shagoal’s chemotherapeutic activity and comparing it to the activity of the conventional chemotherapeutic agent taxol that the researchers discovered an astounding difference. Whereas taxol exhibited clear cytotoxicity in the one-dimensional (flat) monolayer experimental model, it had virtually no effect on the spheroid model, which is a more “real world” model reflecting the 3-dimensionality of tumors and their stem cell subpopulations. Amazingly, this held true even when the concentration of taxol was increased by four orders of magnitude: