. 2021 Jul 1;12:685002. doi: 10.3389/fphar.2021.685002

TABLE 4.

Anti-CRC effect and mechanism of TCM compounds.

Compound name	Main source	Cell lines/model	Dose	Detail	Mechanism	Ref
Berberine	Coptis chinensis	HCA 7 cells	10–100 µM	In vitro	Result in a downregulation of 33 genes differently involved in cell cycle, differentiation and EMT	Palmieri et al. (2019)
Evodiamine	Evodia rutaecarpa	HCT 116 cells	5–15 µM	In vitro	Inhibit the proliferation of cells, cause accumulation of cells in S and G2/M phases, and reduce the levels of the secreted form of AMF	Zhao et al. (2015)
Matrine	Sophora flavescens	SW 480 cells	0.25–1.25 mM	In vitro	Trigger cell apoptosis and G0/G1 cell cycle arrest via mediation of microRNA-22	Liu et al. (2020a)
Matrine	Sophora flavescens	SW 620 cells	0.25–1.25 mM	In vitro		Liu et al. (2020a)
Oxymatrine	Sophora flavescens	RKO cells	0.125–8 mg/ml	In vitro	Inhibit the migration of human colorectal carcinoma via the inhibition of PAI-1 and the TGF-β1/Smad signaling pathway	Wang et al. (2017)
Coptisine	Coptis chinensis	HCT 116 cells	2.81–140.54 µM	In vitro	Induce apoptosis of cells by the PI3K/Akt and mitochondrial-related apoptosis pathway	Han et al. (2018)
Coptisine	Coptis chinensis	BALB/c mice	50–150 mg/kg	In vivo		Han et al. (2018)
Lycorine	Lycoris plants	RKO cells	10–50 µM	In vitro	Induce the activation of the caspase-dependent mitochondrial apoptotic pathway	Wu et al. (2018)
Lycorine	Lycoris plants	SW 480 cells	10–50 µM	In vitro		Wu et al. (2018)
Piperine	Piper longum L.	HT 29 cells	1.25 and 2.5 μg/ml	In vitro	Enhance radiosensitization by inducing the cells to apoptosis	Shaheer et al. (2020)
Sophoridine	Sophora alopecuroide	HCT 116 cells	40–160 µM	In vitro	Inhibits human colorectal cancer progression via targeting the MAPKAPK2	Wang et al. (2019)
		SW 480 cells	40–160 µM	In vitro
		RKO cells	40–160 µM	In vitro
Tetrandrine	Stephaniae tetrandrae radix	SW620 cells	0.2–50 µM	In vitro	Suppress adhesion, migration, and invasion via the inhibition of nuclear factor-kappa B, MMP-2, and MMP-9	Juan et al. (2018)
Vinblastine	Catharanthus roseus	HCT 116 cells	0.3–2.5 nM	In vitro	Inhibit tumor growth and promote angiogenesis factors	Auyeung et al. (2014)
Vinblastine	Catharanthus roseus	BALB/c mice	0.25 mg/kg	In vivo	Inhibit tumor growth and promote angiogenesis factors	Auyeung et al. (2014)
Homoharringtonine	Cephalotaxus fortunei	LoVo cells SW480 cells Caco-2 cells	0.1–0.4 µM	In vitro	Suppress cell growth by inhibiting EphB4 and the PI3K/AKT and MAPK/EKR1/2 signaling pathways	Shi et al. (2020)
			0.1–0.4 µM	In vitro
			0.1–0.4 µM	In vitro
		BALB/C mice	0.25–1 mg/kg	In vivo
Curcumin	Curcuma longa L.	HCT 8 cells	10 µM	In vitro	Downregulate KCNQ1OT1 expression, thus reversing cisplatin resistance in CRC cells	Zheng et al. (2021)
Curcumin	Curcuma longa L.	Nude mice	1 g/kg/week	In vivo		Zheng et al. (2021)
Resveratrol	Veratrum Linn.	DLD-1 cells Caco-2 cells	40–120 µM	In vitro	Regulate several genes involved in the modulation of apoptosis such as PMAIP1, BID, and ZMAT3	Gavrilas et al. (2019)
Resveratrol	Veratrum Linn.	DLD-1 cells Caco-2 cells	40–120 µM	In vitro		Gavrilas et al. (2019)
Quercetin	Sophora japonica L.	Wistar rats	50 mg/kg	In vivo	Suppress DNA damage and induce DNA repair and increase the levels and activities of enzymic, as well as the nonenzymic antioxidants	Darband et al. (2020)
Tanshinone II A	Salvia miltiorrhiza Bge.	SW 620 cells	0.5–10 μg/ml	In vitro	Suppress SW620 proliferation and induce apoptosis	Xue et al. (2019)
Luteolin	Reseda odorata	HT-29 cells SW480 cells SW620 cells LoVo cells	10–100 µM	In vitro	Upregulate miR-384 and downregulate the PTN expression level both in CRC cells and tissues	Yao et al. (2019)
			10–100 µM	In vitro
			10–100 µM	In vitro
			10–100 µM	In vitro
		BALB/c mice	100 mg/kg	In vivo
Genistein	Puerariae lobatae Radix	SW480 cells	25–100 µM	In vitro	Increase the expression of TGF-β1 and lncRNA TTTY18, followed by upregulated Ki-67, serum, and SGK1	Chen et al. (2020a)
Baicalin	Scutellariae Radix	RKO cells	50, 100 μg/ml	In vitro	Inhibit cell growth, migration, and invasion and induce cell apoptosis, induce cell cycle arrest in the G1 phase, and suppress both endogenous and exogenous TGFβ1-induced EMT	Yang et al. (2020)
		HCT 116 cells	50, 100 μg/ml	In vitro
		BALB/c mice	100, 200 mg/kg	In vivo
Shikonin	Arnebiae Radix	SW 480 cells	2.5–15 µM	In vitro	Induce mitochondria-mediated apoptosis by Bcl-2 family protein and increase the intracellular ROS	Liang et al. (2017)
		HCT 116 cells	2.5–15 µM	In vitro
		BALB/c mice	3, 6 mg/kg	In vivo
Emodin	Rhei Radix et Rhizoma	HCT 116 cells	15–60 μg/ml	In vitro	Block the growth and invasion of CRC cells by restraining VEGFR2	Dai et al. (2019a)
Emodin	Rhei Radix et Rhizoma	BALB/c mice	20–80 mg/kg	In vivo		Dai et al. (2019a)
Cordycepin	Cordyceps sinensis	HCT 116 cells	62.5–540 µM	In vitro	Inhibit cell growth by the endogenous Bax-dependent mitochondrial apoptosis pathway	Li et al. (2019b)
Paeoniflorin	Paeonia lactiflora Pall.	HCT 116 cells	2.5–40 mM	In vitro	Inhibit migration and invasion and suppress cell metastatic potential and decrease the expression of HDAC2 and vimentin, increasing E-cadherin	Zhang et al. (2018)
		SW 480 cells	2.5–40 mM	In vitro
		BALB/c mice	1 g/kg	In vivo
Ginsenoside Rh3	Ginseng Radix et Rhizoma	SW 1116 cells	60–240 μg/ml	In vitro	Inhibit proliferation and increase the ratio of apoptotic cells, mRNA, and protein of caspase3	Cong et al. (2020)
Ginsenoside Rh3	Ginseng Radix et Rhizoma	BALB/c mice	100, 200 mg/kg	In vivo		Cong et al. (2020)
Andrographolide	Andrographis Herba	HCT 116 cells	5–100 µM	In vitro	Anti-TNF-α-induced IL-8 by inhibition of NADPH oxidase/ROS/NF-κB and Src/MAPKs/AP-1 signaling pathways	Yuan et al. (2018)
Ursolic acid	Ligustri lucidi Fructus	HCT 116 cells HCT 8 cells	10–40 µM	In vitro	Suppress the invasive by regulating the TGF-β1/ZEB1/miR-200c signaling pathway	Zhang et al. (2019a)
Ursolic acid	Ligustri lucidi Fructus	HCT 116 cells HCT 8 cells	10–40 µM	In vitro		Zhang et al. (2019a)
Celastrol	Tripterygium wilfordii	HCT 116 cells	2.5–10 µM	In vitro	Inhibit proliferation, migration, and NOS activity in the cytoplasm and inhibit growth and migration	Gao et al. (2019)
Celastrol	Tripterygium wilfordii	HT 29 cells	2.5–10 µM	In vitro		Gao et al. (2019)
Bufalin	Bufonis venenum	HCT 116 cells	0.1–50 µM	In vitro	Reverse acquired drug resistance by inhibiting stemness in colorectal cancer cells	Sun et al. (2017)
		LoVo cells	0.1–50 µM	In vitro
		BALB/c mice	1 mg/kg	In vivo
Norcantharidin	Mylabris phalerata Pallas.	HT 29 cells	5, 10 μg/ml	In vitro	Cause proapoptotic and antiglycolytic effects through modulation of Fam46c expression and inhibition of ERK1/2 signaling	Zhang et al. (2020b)
		HT 29 cells	5, 10 μg/ml	In vitro
		LoVo cells SW 620 cells	5, 10 μg/ml	In vitro
Scutellarin	Erigerontis Herba	HCT 116 cells	20–100 µM	In vitro	Reduce viability and induce apoptosis, reduce Bcl-2, and increase Bax and phosphorylation of p53	Yang et al. (2017)
Paeonol	Salvia miltiorrhiza Bge.	HCT 116 cells	7.8125–500 μg/ml	In vitro	Induce G₀/G₁ phase arrest and cell apoptosis by inhibiting the Wnt/β-catenin signaling pathway	Liu et al. (2020b)