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. 2022 Mar 17;11(6):1023. doi: 10.3390/cells11061023

Table 2.

The effects of KDMs pharmacological targeting in HNSCC models.

KDM Inhibitor Target Experimental Model Effects Reference
Tranylcypromine LSD1 In vitro: HN6 and CAL27 cell lines
In vivo:
DMBA- and 4NQO-induced OSCC and xenograft animal models		 Impaired cell proliferation, migration, invasion, as well as induced apoptosis and chemosensitivity.
Reduced xenograft tumor growth.		 [22]
Pargyline LSD1 In vitro: HN6 and CAL27 cell lines
In vivo:
DMBA- and 4NQO-induced OSCC and xenograft animal model		 Impaired cell proliferation, migration, invasion, as well as induced apoptosis and chemosensitivity.
Reduced xenograft tumor growth.		 [22]
In vitro:
SAS, SCC25, SCC4,
and OEC-M1 cell lines		 Reduced cell proliferation and viability. [52]
GSK-LSD1 LSD1 In vitro:
HSC-3 and CAL-27 cell lines
In vivo:
patient-derived tumor xenografts		 Impaired cell proliferation by attenuating EGFR, c-Myc, Wnt/β-catenin, and YAP/TAZ signaling pathways.
Reduced expression of EMT-related genes.
Promoted p53 expression and induced apoptosis.
Reduced tumor size in patient-derived tumor xenografts.		 [23]
Melatonin LSD1 In vitro:
SAS, SCC25, SCC4,
and OEC-M1 cell lines
In vivo: xenograft animal models		 Impaired cell proliferation and induced cell cycle arrest in the G0/G1 phase.
Reduced xenograft tumor growth.		 [52]
IOX-1 KDM3 (dominant target), KDM4, KDM6 In vitro:
Kyse-30, Kyse-410, and OE21 cell lines
In vitro/in vivo:
CAM assay		 Increased radiosensitivity.
Decreased tumor size in vivo.		 [29]
ML324 KDM4 In vitro:
CAL27 and FaDu cell lines		 Reduced cell viability and increased activity of EGFR and PI3K signaling inhibitors (erlotinib, HS-173). [17,75]
CPI-455 KDM5B In vitro:
SCC9, OCTT2, CAL33, and VU147T cell lines
In vivo: xenograft animal models		 Reduced expression of stemness-related genes and attenuated tumorsphere formation without effects on cell viability or apoptosis.
Impaired formation of xenograft tumors.		 [68]
Combination of
GSK-J1 and
Tranylcypromine		 KDM6B
LSD1		 In vitro:
CAL27, FaDu, and HN6 cell lines
In vivo:
4NQO-induced HNSCC and xenograft animal models		 Impaired cell proliferation and induced senescence and apoptosis.
The effects were linked to increased expression of Bax, p16, and p21, as well as a decrease in cyclin D levels.
Suppressed tumor growth and the appearance of less invasive tumors.		 [59]
GSK-J4 KDM6 In vitro:
CAL27 and FaDu cell lines		 Reduced cell viability and increased activity of EGFR and PI3K signaling inhibitors (erlotinib, HS-173). [17,75]
In vitro:
CAL27 and SAS cell lines		 Diminished cell proliferation by downregulating cyclin D1.
Reduced cell migration and invasion capacity, which can be linked to elevated E-cadherin and decreased N-cadherin levels.		 [57]
In vitro: K510 and K30 cell lines
In vivo: xenograft animal models		 Suppressed cell growth and migration. Reduced xenograft tumor growth. [46]
In vitro:
Kyse-150 cell line		 Reduced cell viability, proliferation, migration, and invasion as well as induced cell cycle arrest and apoptosis. [58]
Silibinin KDM8 In vitro:
SAS, SCC25, and HSC3 cell lines
In vivo: xenograft animal models		 Suppressed cell proliferation and reduced xenograft tumor growth at least partly through downregulation of KDM8. [60]