Table 2.
Agents indicated as potentially useful in therapy of HNSCC based on CICs depletion and chemotherapy/radiotherapy.
| Agent | Description | Ref. |
|---|---|---|
| Salinomycin (livestock antibiotic) | Inhibition of cell viability and induction of apoptosis (elevation of Bax/Bcl-2 ratio); Synergistically action with cisplatin and paclitaxel causing higher cell mortality; Reduction of CICs – reduction of sphere formation capacity and suppression of CD44 and BMI-1 expression; Induction of EMT, phosforylation of Akt and up-regulation of miR-328, miR-199a-3p and down-regulation of miR-203. |
123 |
| ABT-737 (BH3 mimetic small molecule inhibitor) | Enhancement of apoptosis and delay of tumor growth in vivo in combination with irradiation; Reduction of CICs(–SP+/CD44high/ALDHhigh cells remain in the sub-G1 phase); cells are more sensitive to irradiation; increase the expression of Bcl-2 family members (except of Bak and PUMA). |
124 |
| Valproic acid (histone deacetylase inhibitor) | Reduction of CICs (reduction of sphere formation capacity, CD44+ population cells and expression of OCT3/4 and SOX2); Inhibition of tumor growth in vitro; Enhancement of cisplatin action – increase of cell mortality by suppressing ABCC2 and ABCC6 transporters, activation of Bax and Caspase3 in CICs population. |
125 |
| Suberoylanilide hydroxamic acid (histone deacetylase inhibitor) | Inhibition of cell proliferation; Reduction of CICs – reduction of sphere formation capacity and Nanog expression; inhibition of tumor growth and metastasis ability in vitro; Enhancement of cisplatin action in cisplatin resistance HPV+ and HPV− cell lines; Lack of additional toxicity in vivo. |
126 |
| Rapamycin (Sirolimus, mTOR inhibitor) | Inhibition of mTOR signaling and reduction of CICs – down-regulation of CD44 and SOX2 (no influence on OCT3/4); Reduction of tumor volume and weight; Reduction of tumor invasion by down-regulation of MMP-2 (no influence on MMP-9). |
127 |
| Curcumin (Diferuloylmethane) with cisplatin | Enhancement of CD133+ cells sensitivity to cisplatin; Reduction of cell colony formation; Decreasing expression of ABCG2 in CD133+ population. |
128 |
| Mesoporous silica nanoparticles (MSNs) with chemotherapeutic drug and siRNA against ABCG2 | Combination of classical drug (5-FU, cisplatin or paxlitaxel) with siRNA against ABCG2 loaded into nanocarrier; Enhancement of drug activity by blocking ABCG2 and breaking multidrug resistance; Enhancement CD133+ cells apoptosis; Reduction of tumor volume and weight. |
129 |
| Gene therapy (RNA restoration or RNA interference) | Restoration of IL-24 in CD133+ cells causing reduction of cell proliferation; Reduction of Snail expression improving sensitivity of ALDH+ cells to chemoradiotherapy. |
113, 130 |