Chlorogenic acid induces cancer cell differentiation through upregulation of SUMO1, leading to c-Myc sumoylation, downregulation of the miR-17 family (miR-20a, -93, -106b), and upregulation of p21, resulting in cell cycle arrest and differentiation phenotype. No specific IC50/Ki/EC50 values for target binding are provided.

In CoCl2-induced hypoxic A549 cells, HIF-1α protein levels can be decreased by 10 μM of chlorogenic acid for 16 hours, but HIF-1α mRNA levels are unaffected [1]. Hypoxia is inhibited by chlorogenic acid (10 μM, 24 h). Huh7 cell proliferation is inhibited by chlorogenic acid (25, 50 μM, 24 h), which also decreases cell migration and number [4]. Induces HUVEC cell migration, thoracic and vascular endothelial cell tube formation [1].

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Chlorogenic acid (CA) at 25–50 μM significantly reduced proliferation, migration, and invasion in human hepatoma (Huh7), lung cancer (H446), glioma (U87MG, M059J), colon cancer (HCT-116), and other solid tumor cell lines. It induced morphological changes (karyopyknosis), increased G0/G1 cell cycle arrest, upregulated differentiation markers (p21, p53, KHSRP), and downregulated undifferentiated markers (c-Myc, CD44, EPCAM). CA also reduced mitochondrial ATP production and oxygen consumption rate (OCR), and inhibited neurosphere formation in glioma cells.
CA treatment increased SUMO1 expression, promoted c-Myc sumoylation, decreased phosphorylated c-Myc, and downregulated miR-17 family members, leading to p21 upregulation.
In human pluripotent stem cells (iPS), CA similarly upregulated p21/p53 and downregulated c-Myc, CD44, and EPCAM.
No cytotoxicity was observed in normal primary human hepatocytes (HH) or non-cancer cell lines (CCC-HEL-1, MIHA, WI-38, MRC-5) at these concentrations.

kg, lateral wall) has a protective effect against experimental reflux esophagitis [3]. Chlorogenic acid (10 mg/kg, intravenous injection) prevents endotoxin death and induced TNF-α release in LPS-intoxicated C57BL/6 nozzles and improves acute liver injury in LPS/GalN-challenged mice [2]. Intraperitoneal injection of chlorogenic acid (25–200 mg/kg) can inhibit tumor growth in NOD/SCID mice with Huh7 or H446 cells [4].

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In a rat model of surgically-induced reflux esophagitis (RE), oral administration of Chlorogenic Acid (CGA) at doses of 10, 30, and 100 mg/kg for 12 days significantly reduced the severity of esophageal lesions. The lesion score (mm²) was attenuated from 44.2 ± 3.6 in the RE control group to 20.9 ± 7.7, 19.6 ± 2.8, and 17.0 ± 3.9 in the CGA 10, 30, and 100 mg/kg groups, respectively. The positive control omeprazole (10 mg/kg) reduced the score to 14.4 ± 5.5. [3]
Chlorogenic Acid (30 mg/kg) significantly attenuated the increase in lipid peroxidation (measured as malondialdehyde, MDA) in esophageal tissue induced by RE (from 1.6 ± 0.1 to 0.8 ± 0.1 nmol/mg protein) and restored the decreased reduced glutathione/oxidized glutathione (GSH/GSSG) ratio (from 5.1 ± 0.7 towards normal levels). [3]
Chlorogenic Acid (30 mg/kg) significantly attenuated the RE-induced increase in serum tumor necrosis factor-α (TNF-α) levels (from 44.9 ± 2.8 to 35.9 ± 2.8 pg/ml). [3]
Chlorogenic Acid (30 mg/kg) significantly attenuated the RE-induced upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in esophageal tissue. [3]
Histopathological examination revealed that Chlorogenic Acid (30 mg/kg) attenuated inflammatory cell infiltration, edema, epithelial thickening, and other pathological changes in the esophagus caused by RE. [3]

A sumoylation assay was performed using a commercial sumoylation assay kit. Nuclear proteins were extracted from cells or tissues, and sumoylation levels were measured according to the kit protocol. CA treatment selectively increased c-Myc sumoylation but not that of IkBα, Rb1, or STAT3.

Cell viability and growth were assessed using MTT assay. Cells were seeded in 96-well plates, treated with CA (25 or 50 μM) every 24 h for up to 6 days, and absorbance was measured at 550 nm.
Migration and invasion assays were performed using Transwell chambers with or without Matrigel coating. Cells were treated with CA for 24 h, seeded in serum-free medium in the upper chamber, and allowed to migrate/invade toward serum-containing medium for 24 h. Cells on the lower surface were stained and counted.
Western blotting was performed using total protein extracts separated by SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against p21, c-Myc, SUMO1, etc.
qRT-PCR was used to measure mRNA and miRNA expression levels using SYBR Green reagent and specific primers.
Flow cytometry was used for cell cycle analysis and CD44 expression using propidium iodide and PE-conjugated CD44 antibody.
Immunofluorescence staining was performed for glioma differentiation markers (GFAP, Tuj1) using specific antibodies and fluorescent secondary antibodies.
ATP levels were measured using a luminescence-based ATP assay kit.
Oxygen consumption rate (OCR) was measured using a Seahorse XF24 analyzer with mitochondrial inhibitors.
Neurosphere formation assay was performed in low-attachment plates with growth factors, and spheres were counted after 14 days.

Animal/Disease Models: Rat experimental reflux esophagitis (RE) [1]
Doses: 10, 30, 100 mg/kg
Route of Administration: Oral
Experimental Results:Reduce esophageal lipid peroxidation (marker: MDA) and increase reflux esophagitis Prototype glutathione/oxidized glutathione ratio. Inhibits the increase in serum TNF-α levels and the expression of iNOS and COX-2 proteins.

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Animal/Disease Models: LPS/GalN-challenged mice [2]
Doses: 10 mg/kg
Route of Administration: intravenous (iv) (iv)injection
Experimental Results: The survival rate of LPS/GalN-intoxicated mice increased. Inhibits LPS/GalN-induced NF-κB p65 or c-Jun phosphorylation without affecting p-IRF3 levels in liver lobules.

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Reflux Esophagitis (RE) Model Induction and Drug Treatment: Male Sprague-Dawley rats (180-200 g) were fasted for 24 hours before surgery. Under anesthesia induced by intraperitoneal injection of ketamine (55 mg/kg) and xylazine (7 mg/kg), a midline laparotomy was performed. To induce RE, the transitional region between the forestomach and the glandular portion was ligated, and the duodenum near the pylorus was wrapped with a piece of catheter (3.0 mm width) which was tied in place to create partial obstruction. Sham-operated rats underwent laparotomy only. After surgery, animals were deprived of food for 48 hours but had free access to water. [3]
Drug Administration: Forty-eight hours after the RE operation, drug treatments began. Chlorogenic Acid was dissolved in saline. Omeprazole (positive control) was dissolved in 0.5% methylcellulose-distilled water. Rats were divided into six groups (n=8-10): Sham (vehicle-treated), RE Control (vehicle-treated), CGA 10 mg/kg, CGA 30 mg/kg, CGA 100 mg/kg, and Omeprazole 10 mg/kg. Drugs or vehicle were administered orally once daily for 12 consecutive days. After the final treatment, rats were fasted for 24 hours and then sacrificed. The entire esophagus was removed for analysis. [3]

The pH of the gastric contents was measured in this study. Treatment with chlorogenic acid (10, 30, 100 mg/kg) had no effect on the pH of the gastric contents (pH was approximately 2.2), which is different from the effect of omeprazole, which significantly increased the pH to 3.6 ± 0.6, indicating that chlorogenic acid does not have acid-suppressing (anti-secretion) activity. [3]

In this study, no specific toxicity or adverse reactions were observed in rats treated with chlorogenic acid (at doses up to 100 mg/kg for 12 days). It was observed to have a protective effect and no toxicity was found. [3] Literature indicates that long-term use of proton pump inhibitors (such as omeprazole) may cause side effects such as gastric acid deficiency or rebound hyperacidity. The property of chlorogenic acid not affecting gastric pH may avoid such acid-suppressing side effects. [3]

[1]. Chlorogenic acid inhibits hypoxia-induced angiogenesis via down-regulation of the HIF-1α/AKT pathway. Cell Oncol (Dordr). 2015 Jan 6.

[2]. IRAK4 as a Molecular Target in the Amelioration of Innate Immunity-Related Endotoxic Shock and Acute Liver Injury by Chlorogenic Acid. J Immunol. 2015 Feb 1;194(3):1122-30.

[3]. Protective Effects of Chlorogenic Acid against Experimental Reflux Esophagitis in Rats. Biomol Ther (Seoul). 2014 Sep;22(5):420-5.

[4]. Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation. Theranostics. 2019 Sep 19;9(23):6745-6763.

Chlorogenic acid is a cinnamic ester formed by the condensation of the carboxyl group of trans-caffeic acid and the 3-hydroxyl group of quinic acid. It is an intermediate metabolite in lignin biosynthesis and plays a role in plant metabolism and food composition. It is both a cinnamic ester and a tannin. Its function is related to (-)-quinic acid and trans-caffeic acid. It is the conjugate acid of chlorogenic acid. Chlorogenic acid has been used in research trials for the treatment of advanced cancer and impaired glucose tolerance. It has been reported to be present in tea (Camellia sinensis), African camellia (Meum athamanticum), and other organisms with relevant data. Chlorogenic acid is a polyphenol, an ester of caffeic acid and quinic acid, found in coffee and black tea, and possesses potential antioxidant and chemopreventive activities. Chlorogenic acid can scavenge free radicals, thereby inhibiting DNA damage and potentially preventing carcinogenesis. Furthermore, this substance may upregulate gene expression involved in immune system activation and enhance the activation and proliferation of cytotoxic T lymphocytes, macrophages, and natural killer cells. Chlorogenic acid can also inhibit the activity of matrix metalloproteinases. It is a naturally occurring phenolic acid with anticancer effects. Studies have shown that it can also prevent paraquat-induced oxidative stress in rats. (Cited from J Chromatogr A 1996;741(2):223-31; Biosci Biotechnol Biochem 1996;60(5):765-68). See also: burdock root (part); artichoke leaf (part). Honeysuckle (part)... See more...

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Chlorogenic acid is an ester of caffeic acid and quinic acid and is one of the most abundant polyphenols in the human diet, found in foods such as coffee. [3] According to previous studies cited in the introduction, it has antioxidant, anti-inflammatory, antibacterial and anticancer activities. [3]
This study shows that chlorogenic acid can protect rats from experimental reflux esophagitis, and its mechanism is related to reducing oxidative stress (lipid peroxidation, increasing the GSH/GSSG ratio) and attenuating inflammatory responses (reducing TNF-α, iNOS, and COX-2 levels), but not by inhibiting gastric acid secretion. [3]
This study shows that chlorogenic acid can be used as an alternative or adjunctive therapy for acid-suppressing drugs in the treatment of reflux esophagitis, and may avoid the side effects of long-term acid-suppressing treatment. [3]

C16H18O9

354.309

354.095

327-97-9

Neochlorogenic acid;906-33-2;Chlorogenic acid-13C3

1794427

White to off-white solid powder

1.7±0.1 g/cm3

665.0±55.0 °C at 760 mmHg

210 °C (dec.)(lit.)

245.5±25.0 °C

0.0±2.1 mmHg at 25°C

1.690

-0.36

6

9

5

25

534

4

C1[C@H]([C@H]([C@@H](C[C@@]1(C(=O)O)O)OC(=O)/C=C/C2=CC(=C(C=C2)O)O)O)O

CWVRJTMFETXNAD-XYXZIBEBSA-N

InChI=1S/C16H18O9/c17-9-3-1-8(5-10(9)18)2-4-13(20)25-12-7-16(24,15(22)23)6-11(19)14(12)21/h1-5,11-12,14,17-19,21,24H,6-7H2,(H,22,23)/b4-2-/t11-,12-,14-,16+/m1/s1

(1S,3R,4R,5R)-3-{[(2Z)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy}-1,4,5-trihydroxycyclohexanecarboxylic acid

3-O-Caffeoylquinic acid; Heriguard; NSC-407296; NSC407296; NSC 407296; 3(34Dihydroxycinnamoyl)quinate; 3(34Dihydroxycinnamoyl)quinic acid; 3Caffeoylquinate; 3Caffeoylquinic acid; 3CQA; 3OCaffeoylquinic acid; Chlorogenate; Heriguard; 3transCaffeoylquinic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~282.24 mM)
H2O : ≥ 20 mg/mL (~56.45 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.06 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.06 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.06 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)