Anticaner; natural product

p-coumaric acid (p-CA) significantly inhibits cell proliferation of A375 and B16 cells in a dose-dependent manner and obviously induced cell morphological changes. p-CA arrested A375 cells in the S phase by downregulating the cell cycle-related proteins Cyclin A and CDK2, and arrested B16 cells in the G0-G1 phase through downregulating the cell cycle-related proteins Cyclin E and CDK2. In addition, p-CA significantly promoted apoptosis of A375 and B16 cells. Furthermore, p-CA significantly upregulated the levels of Apaf1 and Bax and downregulated the levels of Bcl-2, and subsequently increased the levels of cytoplasmic cytochrome c (Cyto-c), cleaved caspase-3, and cleaved caspase-9, leading to apoptosis in A375 and B16 cells. Conclusion: p-CA can significantly inhibit the proliferation of human and mouse melanoma cells in vitro. Our research is a step in the development of anti-melanoma drugs.[1]

Oxidative stress and gut microbial enzymes are intricately linked to the onset of colon carcinogenesis. Phytochemicals that modulate these two factors hold promise for the development of such agents as anticancer drugs. The present study evaluates the chemopreventive potential of p-coumaric acid (p-CA) - a phenolic acid in rats challenged with the colon specific procarcinogen DMH (1,2 di-methyl hydrazine). Rats were randomized into six groups (n=7/group). Group 1 (control); Group 2 (p-CA 200mg/kg b.w.); Group 3 (DMH 40mg/kg b.w.); Groups 4 (DMH+p-CA 50mg/kg b.w.) and Group 5 (DMH+p-CA 100mg/kg b.w.) and Group 6 (DMH+p-CA 200mg/kg b.w.). After the experimental duration of 15 weeks' rats were subjected to necropsy and tissues were collected for the histological and biochemical investigations. DMH induced colonic preneoplastic lesions viz., aberrant crypt foci (ACF), dysplastic ACF (DACF), mucin depleted foci (MDF) and beta catenin accumulated crypts (BCAC) were significantly suppressed by p-CA supplementation. Glucuronide conjugation of DMH in liver and its subsequent deconjugation mediated by microbes in the colon induced the formation of colonic preneoplastic lesions. p-CA inhibited these lesions and protected the rat colon against genotoxic insult by scavenging the free radicals via its strong antioxidant response and detoxification mechanism as measured by TBARS and enzymic antioxidants in control and experimental rats. Of the three tested doses, p-CA at a dose of 100mg/kg body weight is found to exhibit a significant optimum effect compared to the other two doses 50mg/kg body weight and 200mg/kg body weight.[3]

---

P-Coumaric acid (PCA) significantly reversed, nephrotoxicity induced by DOX via lowering BUN, serum Cr and improving histopathological scores as compared to the DOX group. PCA also decreased lipid peroxidation, increased activities of GPx, SOD and CAT, to levels relatively comparable to control. Significant reductions in expression of TNF-α, IL-1β and apoptosis were also observed following Co-administration of PCA relative to the DOX group. Conclusions: Results describe a protective effect of PCA against DOX-induced nephrotoxicity. This effect is likely facilitated through inhibition of oxidative stress, inflammation and apoptosis.[4]

CCK-8 assay was used to detect the effects of p-CA on cell vitality, colony formation assay was used to observe the effects on cell proliferation, Hoechst 33,258 staining was used to observe the morphology of apoptotic cells, flow cytometry was used to detect the effects on apoptosis and the cell cycle, and western blot was used to measure the levels of cell cycle- and apoptosis-related signaling pathway proteins.[1]

Thirty two Wistar rats were divided into control, P-Coumaric acid (PCA), DOX (15 mg/kg, i.p.) and DOX plus PCA (100 mg/kg, orally) groups. DOX-induced nephrotoxicity was indicated by marked increase in blood urea nitrogen (BUN) and serum creatinine (Cr) compared to controls. DOX group also showed elevations in lipid peroxidation and reductions in enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). Expression of renal inflammatory cytokines including tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and apoptosis were also elevated in the DOX group.

mouse LD50 oral 2850 mg/kg BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY); LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION Gendai no Rinsho., 3(675), 1969
mouse LD50 intraperitoneal 1160 mg/kg BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY); LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION Gendai no Rinsho., 3(675), 1969
mouse LD50 intraperitoneal 657 mg/kg Yakugaku Zasshi. Journal of Pharmacy., 104(793), 1984 [PMID:6502467]

[1]. The Anti-tumor Effects of p-Coumaric Acid on Melanoma A375 and B16 Cells. Front Oncol. 2020 Oct 16;10:558414.

[2]. p-Coumaric acid kills bacteria through dual damage mechanisms. Food control, 2012, 25(2): 550-554..

[3]. Protective effect of p-coumaric acid against 1,2 dimethylhydrazine induced colonic preneoplastic lesions in experimental rats. Biomed Pharmacother. 2017 Oct;94:577-588.

[4]. Rafiee Z, et al Doxorubicin-Induced Nephrotoxicity Through Suppression of Oxidative Stress, Inflammation and Apoptosis. Arch Med Res. 2020 Jan;51(1):32-40.

4-coumaric acid is a coumaric acid in which the hydroxy substituent is located at C-4 of the phenyl ring. It has a role as a plant metabolite. It is a conjugate acid of a 4-coumarate.
4-Hydroxycinnamic acid has been reported in Camellia sinensis, Camellia reticulata, and other organisms with data available.
trans-4-Coumaric acid is a metabolite found in or produced by Saccharomyces cerevisiae.
See also: Black Cohosh (part of); Lycium barbarum fruit (part of); Vaccinium myrtillus Leaf (part of) ... View More ...

C9H8O3

164.1580

164.047

C, 65.85; H, 4.91; O, 29.24

501-98-4

p-Coumaric acid-13C3;p-Coumaric acid-d6;2708298-33-1

637542

Off-white to light yellow solid powder

1.3±0.1 g/cm3

346.1±17.0 °C at 760 mmHg

214ºC

177.3±17.4 °C

0.0±0.8 mmHg at 25°C

1.660

1.88

2

3

2

12

178

0

C1=CC(=CC=C1/C=C/C(=O)O)O

NGSWKAQJJWESNS-ZZXKWVIFSA-N

InChI=1S/C9H8O3/c10-8-4-1-7(2-5-8)3-6-9(11)12/h1-6,10H,(H,11,12)/b6-3+

(E)-3-(4-hydroxyphenyl)prop-2-enoic acid

p-coumaric acid; 4-Hydroxycinnamic acid; 501-98-4; p-Hydroxycinnamic acid; trans-4-Hydroxycinnamic acid; 4-Coumaric acid; trans-p-Coumaric acid; 7400-08-0;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

DMSO : ~25 mg/mL (~152.29 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (12.67 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 20.8 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.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (12.67 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 20.8 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.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (12.67 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

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