Application of G-quadruplex targets in gastrointestinal cancers: Advancements, challenges and prospects

Table 5 Overviews of investigations on the effects of small molecule ligands or biomolecules based on G-quadruplex targets in colorectal cancer

Ligands/biomolecules	Cell lines	Targeting gene/G-quadruplex	Effects on G-quadruplex	Effects on genes	Anticancer phenotypes	Ref.
BRACO-19	HCT116, Flavopiridol-resistant HCT116	Telomere	Stabilized G-quadruplex	Not detected	Rapid inhibition of cell growth	[173]
RHPS4 (3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate) and RHPS4-derivatives	HT29, HCT116	Telomere	Bound with G-quadruplex	Induced DNA damage	Stabilized TOPO1, cytotoxicity, inhibited cell proliferation, had synergistic anticancer effects with TOPO1 inhibitors	[174-177]
A series of anthracene derivatives substituted with one or two 4,5-dihydro-1H-imidazol-2-yl-hydrazonic groups	LoVo	Telomere	Induced G-quadruplex structures, bound and stabilized G-quadruplex	Induced DNA damage	Cytotoxicity, telomerase inhibition	[178]
EMICORON	HT29, HCT116, A90 colon epithelial tumor cell line	Telomere	Bound with G-quadruplex	Increased telomere damage	Cytotoxicity, inhibited cell proliferation and tumor growth of patient-derived tumor xenograft	[179,180]
Chromene derivatives	HT29	Telomere RNA	Bound with G-quadruplex	Not detected	Cytotoxicity	[181]
TMPyP4	SW480, SW620	c-MYC	Stabilized the mutated G-quadruplex structure	Inhibited c-MYC expression	Silenced c-MYC expression	[182]
CX-3543 (quarfloxin)	HT29	c-MYC	Not detected	Inhibited c-MYC expression	Reduced CCAT1 expression, promoted cell apoptosis, inhibited cell proliferation and tumor growth of HT29 xenografts	[183]
CX-5461 (pidnarulex)	HT-29, DLD-1, CT26	Telomere, c-MYC, c-kit	Bound with G-quadruplex	Caused DNA damage	Inhibited tumor growth of CT26 xenografts	[184]
Dihydrochelerythrine and its derivatives	HCT116	c-MYC, c-kit	Stabilized G-quadruplex	Not detected	Inhibited cell proliferation	[185]
Unsymmetrical bisacridines derivatives	HCT116	c-MYC, KRAS	Bound and stabilized G-quadruplex	Not detected	Induced cytotoxicity, apoptosis and senescence	[144,186]
7-carboxylate indolo[3,2-b] quinoline tri-alkylamine derivatives	HCT116, SW620	KRAS, HSP90A	Stabilized G-quadruplex	Decreased KRAS and HSP90 mRNA expression, and KRAS transcription	Inhibited cell proliferation and protein expression of KRAS and HSP90A, promoted apoptosis	[187]
3-[2-(Diethylamino)ethyl]-12-methyl-6-oxo-2,3,6,12-tetrahydro-1H-benzo[4,5]imidazo[1,2- a]imidazo[1’,2’:1,6]pyrido[2,3-d]pyrimidin-14-ium bromide	HCT116	KRAS	Bound and stabilized G-quadruplex	Decreased KRAS mRNA expression	Inhibited cell proliferation	[188]
Naphthalene diimides compound T5	Colorectal cancer cell	rDNA	Had high affinity with G-quadruplex	Impaired RNA Pol I elongation, inhibited Pol I transcription	Inhibited cell growth by inducing a rapid inhibition of Pol I transcription, nucleolus disruption, proteasome-dependent Pol I catalytic subunit A degradation and autophagy	[189]
Thiosugar naphthalene diimide conjugates	HT29	Telomere, c-MYC, KRAS	Bound and stabilized G-quadruplex	Not detected	Cytotoxicity	[190]
Gallic acid	SW480 SW620	rDNA, c-MYC	Bound and stabilized G-quadruplex	Inhibited expression of rDNA and c-MYC	Cytotoxicity, inhibited tumor growth of SW480 xenografts	[191]
HnRNPA1	HCT116	TRA2B promoter	Destabilized G-quadruplex	Stimulated TRA2B transcription	Promoted cell proliferation and expression of TRA2B	[192]
SNRPA	HCT116	BAG-1 mRNA	Bound with G-quadruplex	Inhibited translation of BAG-1	Inhibited cell proliferation	[193,194]
PPRHs	SW480	c-MYC	Bound and stabilized G-quadruplex	Inhibited transcription of c-MYC	Inhibited cell proliferation	[159]

PPRHs: Polypurine reverse Hoogsteen hairpins; TOPO: Topoisomerase; KRAS: Kirsten rat sarcoma viral oncogene homologue; HSP90: Heat shock protein 90.