Hepatic Vitamin A Preloading Reduces Colorectal Cancer Metastatic Multiplicity in a Mouse Xenograft Model

Park, Eun Young; Pinali, Daniel; Lindley, Krista; Lane, Michelle A.

doi:10.1080/01635581.2012.687425

Cited by 11 publications

(18 citation statements)

References 44 publications

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“…Park et al have shown that retinol inhibits the growth and the invasion of colon cancer cells in vitro, [18][19][20] and that retinol does not induce apoptosis. However, retinol does affect cell cycle progression in synchronized colon cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Park et al have shown that retinol inhibits the growth and the invasion of RA-resistant colon cancer cells in vitro. [18][19][20] In addition, we have shown that retinol is a more potent suppressor of cancer cell growth and adhesion of several cancer cell lines including refractory cancers (pancreatic, gallbladder, breast, or prostate cancer, and cholangiocarcinoma) than RA or RP in vitro. 21) Most vitamin A actions other than vision are considered to be mediated by RA, which can regulate gene expression by binding to nuclear RA receptors (RAR) or retinoid X receptors (RXR).…”

Section: -7)mentioning

confidence: 99%

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Growth Inhibition of Refractory Human Gallbladder Cancer Cells by Retinol, and Its Mechanism of Action

Imai

Hasegawa

et al. 2017

Biological & Pharmaceutical Bulletin

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Among the constituents of the essential nutrient vitamin A, retinol is a potent suppressor of refractory cancer cell growth linked to tumor progression, showing greater efficacy than retinoic acid (RA). However, the mechanisms of retinol action on human refractory cancer are not known well. In the current study, we examined the actions of retinol on proliferation of human gallbladder cancer NOZ C-1 cells. Retinol and RA inhibited the proliferation of human NOZ C-1 cells in dose-dependent manner, while RA was less potent than retinol. Cell incorporation of RA was approximately two-fold higher than retinol and was not correlated with anti-proliferative activity. Retinol did not affect caspase-3 activity or mRNA expression of Bax and Bcl-2, which are associated with apoptosis. In addition, protein expression of phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK and p-Akt/Akt were not significantly changed by retinol treatment. In contrast, retinol treatment significantly increased the mRNA expression of endoplasmic reticulum (ER) stress factors (heme oxygenase 1 (HMOX1), CCAAT/enhancer-binding protein homologous protein (CHOP), 78 kDa glucose-regulated protein (GRP78), and DnaJ (Hsp40) homolog, subfamily B, member 9 (DNAJB9)). Furthermore, the number of cells in the G 0 /G 1 phase was increased, while the number of cells in the S phase were decreased by retinol treatment. Retinol increased expression of the autophagy-associated protein, LC3-II. These results indicate that retinol is a potent suppressor of gallbladder cancer cell growth by mechanisms that involve ER stress, which results in autophagy and cell cycle delay. This suggests that retinol might be useful for anticancer prevention and therapy in the clinic.

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Section: Discussionmentioning

confidence: 99%

Section: -7)mentioning

confidence: 99%

Growth Inhibition of Refractory Human Gallbladder Cancer Cells by Retinol, and Its Mechanism of Action

Imai

Hasegawa

et al. 2017

Biological & Pharmaceutical Bulletin

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“…37) Previous studies have shown that retinol inhibits the growth and the invasion of RA-resistant colon cancer cells in vitro and in vivo. [19][20][21][22] Retinol reduces invasiveness by decreasing the activity and mRNA expression of matrix metalloprotease and phosphatidylinositol 3-kinase (PI3K) activity, and not through RAR/RXR pathways. In addition, we have shown that retinol may act in refractory cancer cells through mechanisms that are distinct from RAR/RXR.…”

Section: Discussionmentioning

confidence: 99%

“…[19][20][21][22] In addition, we have shown that retinol is a potent suppressor of cancer cell growth and adhesion of several cancer cell lines including refractory cancers in vitro. 23) Retinol suppresses the growth of human gallbladder cancer NOZ C-1 cells to a greater extent than RA, while RP shows no effects.…”

mentioning

confidence: 99%

Effects of Pre- and Post-Administration of Vitamin A on the Growth of Refractory Cancers in Xenograft Mice

Imai

Yamasaki

et al. 2017

Biological & Pharmaceutical Bulletin

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Vitamin A is an essential nutrient that is obtained from the daily diet. The major forms of vitamin A in the body consist of retinol, retinal, retinoic acid (RA), and retinyl esters. Retinal is fundamental for vision and RA is used in clinical therapy of human acute promyelocytic leukemia. The actions of retinol and retinyl palmitate (RP) are not known well. Recently, we found that retinol is a potent anti-proliferative agent against human refractory cancers, including gallbladder cancer, being more effective than RA, while RP was inactive. In the current study, we determined serum retinol concentrations in xenograft mice bearing tumors derived from four refractory cancer cell lines. We also examined the effects of vitamin A on proliferation of human gallbladder cancer cells in vivo. Serum retinol concentrations were significantly lower in xenograft mice with tumors derived from various refractory cancer cell lines as compared with control mice. The growth of tumors was inhibited with increasing serum retinol concentrations obtained post-administration of RP. In addition, pre-administration of RP increased serum retinol concentrations and suppressed tumor growth. These results indicate that administration of RP can maintain retinol concentrations in the body and that this might suppress cancer cell growth and attachment. The regulation of vitamin A concentration in the body, which is critical biomarker of health, could be beneficial for cancer prevention and therapy.

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“…In addition, vitamin A is stored in the liver as retinyl esters. Elevated intestinal lumen and hepatic concentrations of retinol have been attained by dietary vitamin A supplementation (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylinositol 3-Kinase Mediates the Ability of Retinol to Decrease Colorectal Cancer Cell Invasion

Lengyel

Park

Brunson

et al. 2014

Nutrition and Cancer

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Previously, we showed that retinol (vitamin A) decreased both colorectal cancer cell invasion and phosphatidylinositol 3-kinase (PI3K) activity through a retinoic acid receptor-independent mechanism. Here, we determined if these phenomena were related by using parental HCT-116 cells that harbor 1 allele of wild-type PI3K and 1 allele of constitutively active (ca) PI3K and 2 mutant HCT-116 cell lines homozygous for caPI3K. In vitro, treatment of parental HCT-116 cells with 10 μM retinol reduced cell invasion whereas treatment of mutant HCT-116 cell lines with retinol did not. Treatment with 10 μM retinol also decreased the activity of matrixmetalloproteinase-9 and increased tissue inhibitor of matrixmetalloproteinase-I levels in parental, but not mutant, HCT-116 cells. Finally, parental or mutant cells were intrasplenically injected into athymic mice consuming diets with or without supplemental vitamin A. As expected, vitamin A supplementation tended (P = 0.18) to reduce the incidence of metastases in mice injected with the parental cell line and consuming the supplemented diet. In contrast, metastatic incidence was not affected (P = 1.00) by vitamin A supplementation in mice injected with mutant cells. These data indicate that the capacity of retinol to inhibit PI3K activity confers its ability to decrease colorectal cancer metastasis.

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Hepatic Vitamin A Preloading Reduces Colorectal Cancer Metastatic Multiplicity in a Mouse Xenograft Model

Cited by 11 publications

References 44 publications

Growth Inhibition of Refractory Human Gallbladder Cancer Cells by Retinol, and Its Mechanism of Action

Growth Inhibition of Refractory Human Gallbladder Cancer Cells by Retinol, and Its Mechanism of Action

Effects of Pre- and Post-Administration of Vitamin A on the Growth of Refractory Cancers in Xenograft Mice

Phosphatidylinositol 3-Kinase Mediates the Ability of Retinol to Decrease Colorectal Cancer Cell Invasion

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