Table 2.
Target molecules | Inhibitor | Phenotype of targeted cells | Effect | Reference |
---|---|---|---|---|
ZEB2 | miR-200a | CD133/1+ | Reduction of cell migration and invasion | [23] |
MEK | U0126 | Ovcar CD133+/CD44+/CD117+ | Inhibition of ERK2 activation and partial suppression of cisplatin-induced EMT and CSC markers’ expression | [68] |
CXCR4 | AMD3100 | NOY1 CD133+ cells | Inhibition of cell capacity of colony formation, migration and invasion Inhibition of tumorigenicity in vivo |
[26] |
ETRA – endothelin receptor A | BQ123 | CD133+ | Prevention of chemotherapy induced increases in tumor stem cells ETRA inhibition + chemotherapy = reduced formation of tumor spheres |
[18] |
CD133 | Anti-CD133 toxin dCD133KDEL |
NIH:OVCAR5 | Inhibition of in vitro growth of NIH:OVCAR5 cells. Intraperitoneal drug therapy = decrease in tumor progression in peritoneum |
[19] |
CD44 | nanoscale drug delivery system PI, paclitaxel synthetic analog of luteinizing hormone-releasing hormone | Metastatic CD44+ from patient ascites | Suppression of CD44 mRNA and protein, efficient induction of cell death, effective tumor shrinkage, with prevention of adverse side effects on healthy organs | [29] |
Mullerian substance | Mullerian inhibiting substance-MIS or its mimetic SP600125 | CD44+/CD24+/Epcam+ | Shorter tumor-free intervals in vivo, enhanced migration in vitro. Inhibition of CD44+/CD24+/Epcam+ cell growth (previously enhanced by doxorubicin, cisplatin, and paclitaxel) |
[39] |
CD44/EpCAM | RNA-based bispecific CD44 -EpCAM aptamer |
CD44+ cells | Inhibition of cell growth and induction of apoptosis. OC xenograft model: bispecific aptamer suppression of intraperitoneal tumor outgrowth more efficient than single aptamers or their combination. |
[69] |
LIN28 | MIS or MIS mimetic SP600125 | CD44+/CD24+/Epcam+/Ecad- | Decreasing colony formation Inhibition of OC cell growth by induction of G1 through cyclin-dependent kinase inhibitors |
[40] |
Mitochondria | Isoflavone derivative, NV-128 | CD44+/MyD88+ cells | Depression of mitochondrial function and reduction of aggressive phenotype | [35] |
CD44+ | Conventional therapy and fusion cells (CD+ OCIC) | CD44+ cells | Activation of T cells to express elevated levels of IFN-γ with enhanced killing of CD44+ OVCA cells | [30] |
Claudie-4 | Clostridium perfringens enterotoxin (CPE) | CD44+ cells | Intraperitoneal administration of sublethal doses of CPE in mice harboring xenograft=significant inhibitory effect on tumor progression: cure and/or long-term survival of all treated animals |
[43] |
CD44 | miR-199a | CD44+/CD117+ OCICs | Increase of chemosensitivity of ovarian CICs to cisplatin, paclitaxel, Adriamycin; reduction of ABCG2 and stemness markers’ expression; suppression of xenograft tumor growth | [44] |
Survival-promoting mitochondria complex of hexokinase II and VDAC |
3bromopyruvate | SKOV3 CD44+/CD117+/ALDH1+ cells | Sensitivity to combination treatment with significantly lowered doses of cisplatin | [32] |
ETRA/ETRB | Macitentan or combination of ETRA & ETRB antagonists BQ123 & BQ788 | CD133+ CSLCs | No enhancement of antitumor immune cell recruitment. In vitro prevention of ICAM 1 induction. Prevention of chemotherapy-induced increases in tumor stem cells. Macitentan alone= non-significant anti-tumor activity in vivo ą-combined with chemotherapy= reduction of tumor growth (CD133+ CSCs) combined with chemotherapy = reduction of sphere formation |
[18] |
IL-17 and its downstream pathways NF-kB and p38 MAPK signaling pathways | IL-17R-neutralizing antibody PDTC and SB203580 |
CD133+ A2780 cells | Sphere reduction | [21] |