Antitumor Alkaloids in Tibetan Corydalis: Chemical Diversity and Pharmacological Insights

Linguo Cao; Lijun Liu; Yanyan Wang; Jiaqing Liu; Zuowu Xi

doi:10.12659/MSM.947268

25 June 2025 : Review article

Antitumor Alkaloids in Tibetan Corydalis: Chemical Diversity and Pharmacological Insights

Linguo Cao^{ABE 1}, Lijun Liu^{C 2}, Yanyan Wang^{D 1}, Jiaqing Liu^{E 1}, Zuowu Xi^{EFG 3*}

DOI: 10.12659/MSM.947268

Med Sci Monit 2025; 31:e947268

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Introduction Phytochemical Research Pharmacologically Guided Q-Marker Discovery: From Compound Identification to Mechanistic Elucidation Chemotaxonomic Profiling: From Species Differentiation to Geo-Authenticity Assessment Analytical Technology Revolution: From Single-Component Quantification to Multi-Omics Integration Tradition Meets Innovation: Processing and Compatibility-Driven Q-Marker Modulation Clinical Applications Cell Cycle Arrest Induction of Tumor Cell Apoptosis Regulation of the MAPK Signaling Pathway Suppression of Tumor Angiogenesis Conclusions Future Directions References

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Table 4 Summary of antitumor effects of Corydalis alkaloids: Test models, dosage, duration, and major findings.

Active ingredient	Test model	Dose	Duration	Major findings	Ref
13-oxoprotopine []¹	SW480	200 μg/mL	24 h, 48 h	––	[]⁶⁰
Protopine []⁴	PANC-1 cells	5, 10, 20 μM, 20 mg/kg	48 h, 20 days	The expression of mitochondria-mediated apoptosis proteins↑	[]³⁸
	Xenograft tumor model in BALB/c nude mice (HepG2, Huh-7)	5, 10, 20 mg/kg	30 days	Activating PI3K/Akt, cleavaged caspase-3↓	[]⁶¹
	HCT116	10, 20, 40 μM	15 h	The expression of p21WAF1/CIP1 and Bax↓	[]⁶²
	SW480	1000 μg/mL	––	––	[]⁵⁰
	MDA-MB-231	30, 100 μM	1.5 h	EGFR, ICAM-1, αv-integrin, β1-integrin and β5-integrin↓	[]⁶³
	PC-3, DU-145	30, 50 μM	24 h	Cdk1 activity and Bcl-2↓	[]⁶⁴
	A549	100 μg/mL	––	––	[]⁵⁰
	T47D, MCF-7	25 μM	48 h	Blocked in G2/M and G0/G1 phases	[]⁶⁵
	Bel7402	50 μM	24 h	Arrested in the G1phase	[]⁶⁶
	Xenograft tumor model in BALB/c nude mice(HepG2, Huh-7)	120 mg/kg	20 day	Caspase 3, caspase 8 and caspase 9 activated↑	[]⁶⁷
	HepG2	50, 100 μM	2 h, 4 h, 6 h	Cyclin D1↓ in dose - and time-dependent manner	[]⁶⁸
	MDA-MB-231	20, 40 μM	24 h	Arrested the cell cycle in the S phase	[]⁶⁸
	NVP-AUY922-insensitive CRC cells	5, 10 μM	24 h	microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1↓	[]⁶⁹
	HBT-94	10, 30, 50, 100 μM	6 h, 12 h, 24 h	Regulated the PI3K/Akt and p38, the expression of p53 and p21↑, arrested in G2/M phase	[]⁷⁰
Berberine []¹⁵	ERMS1 cells	1, 3, 10 μM	72 h	Inhibited the cell cycle at G1 phase	[]⁷¹
Coptisine []¹⁶	A549	50, 25, and 12.5 μM	48 h	Activated caspase9/8/3↑, poly adenosine diphosphate ribose polymerase↓, ROS, Bax/Bcl-2 ratio↑	[]⁷²
	HCT-116 cells	14.05 μM	12 h, 24 h, 36 h, 48 h	PI3K/Akt↓, mitochondrial-mediated apoptotic pathway↑	[]⁷³
	SMMC7721 cells	12.5, 25, 50, 100 μM	24 h	67LR activation↑, cGMP↑, caspase8/3 activation↑	[]⁷⁴
	PANC-1 cells	25, 50, 100 μM	48 h	G1 phase arrest↑, S phase↓, phosphorylated of ERK and total ERK levels↓	[]⁷⁵
	HepG2 with low level of miR-122, Kunming mice	25 μg/mL, 37.5, 150 mg/kg	24 h, 7 days	miR-122↑, Bax, cleaved-casp3↑, Bcl-2↓	[]⁷⁶
	HCT116, Xenograft tumor models	20, 40, 80 μg/ml, 30, 60, 90 mg/kg	24 h, 21 days	Via PI3K/AKT signaling pathway, MMP-2, MMP9, MFG-E8↓	[]⁷⁷
	HCT-116, male BALB/c nude mice	5 μg/mL, 50, 100, 150 mg/kg	48 h, 25 days	the transcription of KRAS and TNF-β↓ via MAPK pathway, the expression of p53↑	[]⁷⁸
	TE1, KYSE450 cells	5, 10, 20 μM	24 h	ERK1/2 and P38 signaling↓, claudin-2, CDK1 cyclin B1↓	[]⁷⁹
	HepG2 and Huh-7, NOD-SCID immunodeficient mice	1, 2.5,5, 10μg/mL, 50, 100, 150 mg/kg	24 h, 25 days	MAPK, RAS-ERK pathway↓, G1-phase cell cycle arrest, activation of caspase3/8/9↑	[]⁸⁰
	HepG2, Huh7 cells, male BALB/c nude mice	25 μg/mL, 120.13, 150 mg/kg	24 h, 30 days	The protein expression of ADAM10, MMP-9, the ratio of Bcl-2/Bax↓	[]⁸¹
	CMT-U27 cells, BALB/c nude mice	5, 10, 20 μM, 50 mg/kg	18 h, 21 days	PI3K/AKT/mTOR pathway↓	[]⁸²
	A549	50, 25, and 12.5 μM	48 h	Activated caspase9/8/3↑, poly adenosine diphosphate ribose polymerase↓, ROS, Bax/Bcl-2 ratio↑	[]⁷²
Palmatine []²⁴	ERMS1 cells	1, 3, 10 μM	72 h	Inhibited the cell cycle of all RMS cells at G1 phase	[]⁷¹
Scoulerine []²⁶	OVCAR3 cells, BALB/c nude mice	5, 10 μM, 1, 2.5, 5, 10 mg/kg	24 h, 16 days	PI3K/Akt/mTOR pathway↓	[]⁸³
	Jurkat, MOLT-4	5 μM	24 h	ATR and ATM kinase-dependent cell cycle checkpoint signaling↑	[]⁸⁴
	SW480, HT29 cells	4, 8 μM	48 h	ROS-mediated ER stress↑	[]⁸⁵
	RPE-MYCBcl2 cells	2, 4 μM	46, 72 h	Centrosome amplification and declustering↑	[]⁸⁶
	B16F10, A375	5,10,20 μM	24 h	By γ-H2AX accumulation, ROS and subsequent DNA damage↑	[]⁸⁷
Corynoline []⁵²	EU-4 cells lack p53 expression and express very low levels of MDM2	1, 10, 50, 100 μM	24, 48, 72 h	XIAP↓	[]⁸⁸
	MDA-MB-468	55 μM	24 h	Induce apoptosis by regulating the p38 MAPK pathway	[]⁸⁹
	HepG2, MHCC97-L	50, 100, or 200 μM in HepG2 cells and 100, 200, or 400 μM in MHCC97-L cells	6 h	Bax↑, PT channels, cytochrome C↑, activated caspase 3/9↑	[]⁹⁰
	HepG2	125 μm	24, 48, 72,96 h	CD147↓, MDR1↑, drug sensitivity↑	[]⁹⁰
Sanguinarine []⁵⁷	HL-60	0.5, 1, 3, 5, 10 mM	24 h	Caspase 3/7 activated↑	[]⁹¹
	MG-63, SaOS-3	1, 5 μmol/L	4, 24 h	Mitochondrial membrane potential↑, chromatin concentration and apoptotic bodies↑	[]⁹²
	HT-29	0.5, 1, 2 μmol/L	24 h	Caspase 3/9↑ and Bcl-2/Bax ratio↑	[]⁹³
	SAS cells	0.25, 0.5, 0.75, 1 μM	24 h	Phosphorylated of total ERK1/2, total p38, and JNK1/JNK2↓, caspase and the Bax/Bcl-2 ratio↑	[]⁹⁴
	BALB/c nude mice, HCC cell	10 mg/kg, 8 μM	48 h, 30 days	Inducing cell cycle arrest and reactive oxygen species (ROS)-associated apoptosis↑	[]⁹⁵
	BALB/c nude mice, DU145 Cells	1, 2, 5μM, 0.5 mg/kg	6 h,7 days	The expression of survivin protein↓	[]⁹⁶
Sanguinarine []⁵⁷	Patu-8988 and Panc-1, xenograft model of PDAC	25, 50, 100, 200, 400 μM, 25, 50 mg/kg	24 h, 18 days	CHOP depenndt ER stress↑, ROS production and activating p38↑	[]⁹⁷
Tetrahydrocorysamine []⁶⁸	DU145, LN-S17 cells	2, 4 μM	4 h	Phosphorylation of Stat3 in Tyr705 and Ser727↓	[]⁹⁸
Corynoxine []⁹³	HCT-116, HT-29, nude mice xenograft modeling	5, 10 μM, 2.5, 5 mg/kg	24 h, 4 weeks	S phase arrest↑, Wnt signaling pathway↓ by β-catenin and GSK-3β expression. E-cadherin↑, N-cadherin↓	[]⁹⁹
Jatrorrhizine []¹⁰⁰	MDA-MB-231, MCF-7 cells, orthotopic 4T1 tumor-bearing mouse	10, 20μM, 2.5, 5 mg/kg	24 h, 4 weeks	Wnt/β-catenin signaling and EMT↓	[]¹⁰⁰
	C8161 cells, BALB/C nude mice	10, 40, 80, 160, 320 μM, 50 μg	48 h, 14 days	G0/G1 cell cycle arrest, p21 and p27↑. VE-cadherin expression↓	[]¹⁰¹
pRb – Retinoblastoma Protein; CDKs – cyclin-dependent kinases; Chks – checkpoint kinases; PI3K/Akt – phosphatidylinositol 3-kinase/protein kinase B; MAPK – mitogen-activated protein kinase; p53 – tumor suppressor protein p53; p21 – cyclin-dependent kinase inhibitor 1; Apaf-1 – apoptotic protease-activating factor 1; c-IAP1 – cellular inhibitor of apoptosis protein 1; XIAP – X-linked inhibitor of apoptosis protein; Bcl-X – B-cell lymphoma-extra large; BNIP3 – Bcl-2/adenovirus E1B 19 kDa protein-interacting protein 3; VEGF – vascular endothelial growth factor; COX-2 – cyclooxygenase-2; IL-1β – interleukin-1 beta; HIF – hypoxia-inducible factor; TNF-α – tumor necrosis factor-alpha; CREB – cAMP response element-binding protein; GM-CSF – granulocyte-macrophage colony-stimulating factor; ATF-2 – activating transcription factor 2; STAT3 – signal transducer and activator of transcription 3; EMT – epithelial–mesenchymal transition; TOPOI – DNA topoisomerase I); ↓, ↑ – represents down-regulation, and upregulation.

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Antitumor Alkaloids in Tibetan Corydalis: Chemical Diversity and Pharmacological Insights

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