Table 1.

Main in vitro and in vivo effects of chemotherapeutic agents in combination with plant-derived bioactive components against CRC.

Drug	Plant-Derived Bioactive Component	Experimental Model	Main Effect	Molecular Target	Ref.
5-FU	Curcumin	HCT-8 HCT-8/5-FU (5-FU-resistant)	Reversal effects on the multidrug resistance	↓ P-gp HSP-27	[52]
		SW-480	Enhance the therapeutic effects of 5-FU Induction of ROS	↓ Sp1, Sp3, Sp4, miR-27a	[53]
		HCT116/ HCT116-5FUR SW480/SW480-5FUR	Suppressed EMT	↑ miR-200b, miR-200c, miR-141, miR-429, miR-101 ↓ BMI1, SUZ12, EZH2 mRNA	[54]
	EGCG	DLD-1	Synergistic growth suppression, apoptosis	-	[24]
		HCT-116	Promotes cancer cell apoptosis and suppressed EMT	↓ GRP78, MDR1, Bcl-2 ↑ miR-155-5p, caspase-3 PARP, Bad	[23]
	Resveratrol	DLD-1	Synergistic growth suppression, apoptosis	miR-34a/E2F3/Sirt1 cascade	[24]
		DLD1 HCT116	Enhanced the antiproliferative potential of 5-FU Augmented 5-FU pro-apoptotic effect Repressed EMT transition	↓ Akt and STAT3 pathways ↓ slug and vimentin	[57]
		HT-29 SW-620 CRC	Enhanced ROS and lipid peroxides	↓ AKT, STAT3	[58]
		HCT116/HCT116R in 3D-alginate tumor microenvironment	Suppressed EMT	↓ TNF- β, vimentin, slug ↑ E-cadherin	[59]
Cisplatin	EGCG	DLD-1 HT-29	Synergistic effect on inhibition of cell proliferation and induction of cell death	↑ LC3-II	[60]
Oxaliplatin	Curcumin	HT29/HTOXAR3 DLD1/DLDOXAR3 LoVo/LoVOXAR3	Re-sensitized oxaliplatin-resistant cells	↓ NF-κB, CXCL8, CXCL1, CXCL2 ↓ Akt pathway	[61]
		HCT116/OXA xenograft mice	Reverse oxaliplatin resistance-reduced tumor weight and volume	↓ Smad2/3	[62]
	Difluorinated-Curcumin	HCT116 xenograft mice	Re-sensitize drug-resistant mice	miR-21-PTEN-Akt axis	[63]
	Resveratrol	Caco-2	Reduce cell growth immunomodulator	↑ caspase-3, PARP	[64]
		HT-29 HCT-116	Sensitized cells to oxaliplatin	↑ miR-34c ↓ KITLG	[65]
		HCT116 xenograft mice	Augmented efficacy on suppressing tumor growth	-	[65]
		HCT116	Antichemosensitizing effect	↑ survivin	[66]
	Betulinic acid	SNU-C5/OXT-R	Sensitized cells to oxaliplatin	↓ Bcl-2 ↑ Bad	[67]
	Alanolactone	HCT-116	Induction of ROS Enhanced the effect of oxaliplatin	JNK, p38 MAPK apoptotic pathways	[68]
	Piperlongumine	HCT-116 LoVo	Sensitizes cells to oxaliplatin Enhances oxaliplatin-associated ROS production	↓ Bcl-2 ↑ Bax, ER-stress- associated proteins (eIF2α, ATF4, CHOP)	[69]
Irinotecan	Curcumin	LoVo HT-29	Enhanced the effects of irinotecan in inhibiting colorectal cancer cell viability Enhanced the anti-tumor activity of irinotecan through reactive oxygen species generation	-	[70]
		LoVo/CPT-11 (irinotecan-resistant cells)	Significantly attenuated chemoresistance to irinotecan through induction of apoptosis of CSCs	↓ CD44, EpCAM, CD24, Bcl-2 ↑ Bax	[71]
		LoVo/CPT-11R	Suppressed EMT	↑ E-cadherin ↓ vimentin, N-cadherin	[72]
		Irinotecan-treated BALB/c nude mice	Protective effect against irinotecan-induced intestinal mucosal injury	↓ NF-κB	[73]
	EGCG	RKO HCT116	Stronger inhibitory effect on tumor cells Prevention of migration and invasion S or G2 phase arrest induction of apoptosis	↓ topoisomerase I	[74]
Doxorubicin	Resveratrol	HCT116	Sensitize colorectal cancer cells to doxorubicin via facilitating apoptosis and enhancing intracellular entrapment	↑ Bax ↓ P-gp	[75]
		Multidrug-resistant Caco-2	Inhibition of ABC-transporters’ efflux functions	↓ P-gp, MRP1, BCRP, CYP3A4, GST, hPXR mRNA	[76]

↓—increased, ↑—decreased.