Tri-phenyl-phosphonium (TPP) is a non-toxic chemical moiety that functionally behaves as a mitochondrial targeting signaling in living cells. TPP-related compounds may be utilized to target mitochondria in cancer stem cells (CSCs), and may be used for treating and/or preventing tumor recurrence, metastasis, drug resistance, and/or radiotherapy resistance, as well as for anti- cancer therapies. Various TPP-related compounds validated for oxygen consumption inhibition (OCR), were non-toxic, and had little or no effect on ATP production in normal human fibroblasts. Yet these compounds selectively target adherent "bulk" cancer cells. These compounds also inhibit the propagation of CSCs in suspension. TPP-related compounds provide a novel chemical strategy for effectively targeting both i) "bulk" cancer cells and ii) CSCs, while specifically minimizing or avoiding off-target side-effects in normal cells, among other useful therapies.
