Retinyl acetate (10 μM) suppresses cell growth (such as melanoma cell lines B 16 and S91, the inhibition rates are 48% and 79% respectively) [2].

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The study evaluated the growth inhibitory effects of retinyl acetate (at a concentration of 10⁻⁵ M) on 31 untransformed, transformed, and tumor cell lines in vitro. Cells were categorized based on their sensitivity: (a) Cells not affected (<10% inhibition) or only slightly inhibited (<25%) by retinyl acetate, including untransformed BHK and CHO-K1-pro cells, virally transformed PyBHK, human fibrosarcoma HT1080, and others like untransformed Balb/3T3, SV3T3, MSV3T3, and chemically transformed BP3T3. (b) Cells exhibiting growth inhibition (25-50%), such as neuroblastoma C1300 (40% inhibition), mouse mammary adenocarcinomas M12 and DD3, human breast carcinosarcoma H,0578, and murine lymphomas S49 and EL4. (c) Cells that were moderately growth inhibited (50-75%), including mouse sarcoma S180, mastocytoma P815 (21% inhibition), rat mammary adenocarcinoma R3230AC, and others. (d) Cells extremely sensitive to retinyl acetate (growth inhibited >75%), such as murine melanoma S91 (79% inhibition), rat mammary adenocarcinoma 13762NF, murine lymphosarcoma RAW117, and others. In most cases, retinoic acid was more potent than retinyl acetate, but for some cell lines (e.g., C1300 neuroblastoma, S91 melanoma, Mm5mT, and 13762NF mammary adenocarcinomas), retinyl acetate was nearly as active. [2]

The progression of Sprague-Dawley tumors produced by DMBA is inhibited by retinyl acetate (250 mg/kg in diet) [1].

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Administration of retinyl acetate in the diet (250 mg per kg of diet) significantly inhibited mammary carcinogenesis induced by N-methyl-N-nitrosourea (NMU) in female Sprague-Dawley rats. It reduced both the incidence and the total number of mammary cancers (including benign tumors) across different NMU dose groups. Additionally, retinyl acetate markedly prolonged the latency period for the appearance of palpable mammary tumors. For instance, in rats treated with a high dose of NMU, the time to first palpable cancer was approximately doubled compared to the placebo control group. No mammary cancers developed in rats receiving the low dose of NMU along with retinyl acetate by the end of the experiment (175 days). [1]

Cell growth inhibition was assessed using a standardized assay. Briefly, cells (0.5-1.0 x 10⁵) were seeded in growth medium in culture dishes. The test groups received fresh growth medium containing retinyl acetate at a final concentration of 10⁻⁵ M, dissolved in 0.1% ethanol. Control groups received medium with 0.1% ethanol only. All procedures involving retinoids were performed under subdued light, and culture dishes were wrapped in aluminum foil. Cells were incubated at 37°C in a humidified atmosphere of 13% CO₂. Monolayer or multilayer cultures were refed with fresh medium every third day. Suspension cultures were refed by adding fresh medium to the existing culture. Cells were grown until control cultures were nearly confluent (typically 5-6 days) or, for suspension cells, until control cells underwent five to six replication cycles. At the endpoint, adherent cells were detached using EDTA in calcium- and magnesium-free PBS and counted using an electronic particle counter or hemacytometer. Cell viability was assessed by trypan blue exclusion. The percent inhibition of proliferation was calculated relative to control cultures. Experiments were performed at least twice in duplicate. [2]

Female Sprague-Dawley rats, 42 days old, were used. At 50 days of age (average weight 150g), rats received an intravenous injection of NMU dissolved in physiological saline (adjusted to pH 5.0) at doses of 5.0, 2.5, or 1.25 mg per 100g body weight. A second injection of NMU or saline (for controls) was administered 7 days later. Three days after the second injection, all rats were placed on experimental diets for the remainder of the study. Retinyl acetate was blended into the standard stock diet in the form of stable gelatinized beadlets at a concentration of 250 mg per kg diet. Control groups received placebo beadlets without the retinoid. Rats were palpated twice weekly for mammary tumor detection, weighed twice weekly, and observed daily for signs of toxicity. All animals were sacrificed 175 days after the initial NMU injection, and mammary tumors were excised for histological examination. [1]

The article mentions that the carcinogen NMU has a half-life of only a few hours at human pH. However, the article does not describe the ADME or pharmacokinetic parameters of retinoic acid itself (e.g., absorption, distribution, metabolism, excretion, half-life, oral bioavailability). [1]

In this study, no signs of vitamin A overdose (retinoid toxicity) were observed in rats fed retinyl acetate. The body weight and liver histology of rats treated with retinyl acetate were essentially the same as those of rats in the placebo control group. Vaginal smears of rats fed retinyl acetate showed normal estrous cycles, indicating that there were no significant changes in ovarian steroid metabolism. The inhibitory effect on carcinogenicity was not due to the general toxicity of the compound. [1] In cell culture experiments, the growth inhibition induced by retinyl acetate was not due to direct cytotoxicity. Daily observation of cultures exposed to 10⁻⁵ M retinyl acetate showed no increase in cell debris or detached cells. During the experimental period (5–8 days), the survival rate of cells treated with retinoic acid was consistently above 90%, similar to the survival rate of untreated control cells. [2]

[1]. Retinyl acetate inhibits mammary carcinogenesis induced by N-methyl-N-nitrosourea. Nature. 1977 Jun 16;267(5612):620-1.

[2]. Lotan R, Nicolson GL. Inhibitory effects of retinoic acid or retinyl acetate on the growth of untransformed, transformed, and tumor cells in vitro. J Natl Cancer Inst. 1977 Dec;59(6):1717-22.

Retinyl acetate is an acetate ester. It is functionally related to all-trans retinol. Retinyl acetate is a natural fatty acid ester form of retinol (vitamin A) with potential antitumor and chemopreventive activities. Retinyl acetate can bind to and activate retinoid receptors, thereby inducing cell differentiation and inhibiting cell proliferation. This substance can also inhibit carcinogen-induced tumor transformation in certain cancer cell types and has immunomodulatory properties. (NCI04)

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Retinyl acetate is a retinoid (vitamin A analog). This study shows that retinyl acetate effectively prevents experimental breast cancer in an NMU-induced rat breast cancer model. Compared with other models (such as DMBA-induced cancer models), the NMU-induced breast cancer model is closer to human breast cancer in terms of invasiveness, hormone dependence, and metastasis. The mechanism by which vitamin A-like substances inhibit breast cancer development is not fully elucidated, but some studies suggest it may be related to maintaining normal epithelial cell differentiation. The authors noted that although no toxicity was observed in this study, the potential toxicity of retinyl acetate makes the development of novel synthetic vitamin A derivatives with higher activity and lower toxicity particularly important. [1] Retinyl acetate is a vitamin A derivative (vitamin A derivative). This study showed that it can directly inhibit the in vitro proliferation of a variety of transformed cell lines and tumor cell lines, suggesting that the antitumor activity of vitamin A derivatives observed in vivo may at least partly stem from its direct effect on tumor cell growth, rather than just indirect mechanisms such as immune regulation. Its mechanism of action is not fully elucidated, but may involve interaction with specific intracellular binding proteins, thereby affecting DNA synthesis. Different cell lines have different sensitivities to vitamin A derivatives, suggesting that screening tumor cells for vitamin A derivatives in vitro may help predict their potential response to vitamin A derivative therapy. [2]

C22H32O2

328.4883

328.24

127-47-9

Retinyl acetate-d4;118139-40-5

638034

Light yellow to yellow solid powder

1.0±0.1 g/cm3

440.5±14.0 °C at 760 mmHg

57-58 °C

124.8±18.5 °C

0.0±1.1 mmHg at 25°C

1.532

7.39

0

2

7

24

596

0

CC1=C(C(CCC1)(C)C)/C=C/C(=C/C=C/C(=C/COC(=O)C)/C)/C

QGNJRVVDBSJHIZ-QHLGVNSISA-N

InChI=1S/C22H32O2/c1-17(9-7-10-18(2)14-16-24-20(4)23)12-13-21-19(3)11-8-15-22(21,5)6/h7,9-10,12-14H,8,11,15-16H2,1-6H3/b10-7+,13-12+,17-9+,18-14+

[(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenyl] acetate

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 : ~50 mg/mL (~152.21 mM)
H2O : ~0.67 mg/mL (~2.04 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.61 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: ≥ 2.08 mg/mL (6.33 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.

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Solubility in Formulation 3: 2 mg/mL (6.09 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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