Carnosic acid suppresses colon tumor formation in association with antiadipogenic activity

Kim, Yun-Ji; Kim, Jong-Sang; Seo, Young Rok; Park, Jung Han Yoon; Choi, Myung‐Sook; Sung, Mi‐Kyung

doi:10.1002/mnfr.201400293

Cited by 34 publications

(19 citation statements)

References 46 publications

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“…Correspondingly, the number of colon tumors in mice nurtured with HFD supplemented with carnosic acid reduced to 6.7-8.4 in comparison to 12.7 tumors in HFD mice [33]. This study thus highlights the anti-adipogenic activity of carnosic acid in addition to its anti-carcinogenic activity.…”

Section: In Vivo Studiesmentioning

confidence: 68%

“…Metabolomics study showed increase in reduced intracellular GSH levels in treated HT-29 cells further demonstrating the chemopreventive response of these cells to carnosic acid treatment[31]. In a different study 1µM and 10µM of carnosic acid inhibited growth of HT-29 cells by exhibiting significant accumulation of cells in the S phase with decreased expression of cyclinD1 and CDK4 along with apoptosis induction[33]. Interestingly, this study highlights the use of carnosic acid in alleviating adiposity related acceleration of colon cancer formation.…”

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confidence: 87%

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Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity

2015

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Section: In Vivo Studiesmentioning

confidence: 68%

mentioning

confidence: 87%

Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity

2015

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“…Of note, levels of GSH, an important antioxidant, were enhanced and levels of N -acetylputrescine, which are toxic in high doses, were decreased [51]. In HT-29 cells co-cultured with 3T3-L1 adipocytes, CA attenuated the negative effects of the adipocytes on the colon cancer cells by inhibiting triglyceride accumulation and downregulating expression of the Ob-R receptor [52]. In these cells CA also inhibited cell viability by decreasing phosphorylation of the cell survival regulators Akt and Bcl-xL and enhancing Bax expression.…”

Section: Anticancer Effects Of Carnosic Acid (Ca): In Vitro Studiesmentioning

confidence: 99%

“…In these cells CA also inhibited cell viability by decreasing phosphorylation of the cell survival regulators Akt and Bcl-xL and enhancing Bax expression. Furthermore, cell cycle arrest was induced by inhibition of cyclin D1 and CDK4 [52]. Similarly, a fraction of rosemary extract which was found to consist mainly of CA (98.7% pure) was tested on HT-29, SW480 and HGUE-C-1 colon cancer cells and significantly inhibited cell viability.…”

Section: Anticancer Effects Of Carnosic Acid (Ca): In Vitro Studiesmentioning

confidence: 99%

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

2016

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Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival. Compounds of plant origin, including food components, have attracted scientific attention for use as agents for cancer prevention and treatment. The exploration into natural products offers great opportunity to evaluate new anticancer agents as well as understand novel and potentially relevant mechanisms of action. Rosemary extract has been reported to have antioxidant, anti-inflammatory, antidiabetic and anticancer properties. Rosemary extract contains many polyphenols with carnosic acid and rosmarinic acid found in highest concentrations. The present review summarizes the existing in vitro and in vivo studies focusing on the anticancer effects of rosemary extract and the rosemary extract polyphenols carnosic acid and rosmarinic acid, and their effects on key signaling molecules.

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“…Cellular mechanisms involved in the effects of carnosic acid include up-regulation of Nuclear factor (erythroid-derived 2)-like 2 (Nfr2) activity [8, 13,55,56], preservation of mitochondrial respiratory function [11,56], mitochondrial depolarization [47], cytochrome-c release [36], increase in Bax:Bcl-2 ratio [36], caspase activation [36,37], up-regulation of NAD + -dependent deacetylase SIRT1 [2], glutathione S-transferase [8,57], death receptor (DR)5 [19], Bcl-2 interacting mediator of cell death (Bim) [19] and p53 up-regulated modulator of apoptosis (PUMA) [19] expression, down-regulation of c-FLIP and Bcl-2 expression [19] as well as stimulation of PGE 2 synthesis [15]. Signaling involved in the effect of carnosic acid further includes phosphatidylinositol 3-kinase (PI3K)/Akt [26,[46][47][48][49], nuclear factor-kappa B (NF-κB) [21,49], and p38 kinase [8, 16,45,57].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Eryptosis Following Exposure to Carnosic Acid

Stockinger¹,

Bissinger²,

Bouguerra³

et al. 2015

Cell Physiol Biochem

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Background/Aims: The phenolic abietane diterpene component of rosemary and sage, carnosic acid, may either induce or inhibit apoptosis of nucleated cells. The mechanisms involved in the effects of carnosic acid include altered mitochondrial function and gene expression. Human erythrocytes lack mitochondria and nuclei but are nevertheless able to enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms involved in the stimulation of eryptosis include oxidative stress, increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), and ceramide formation. The present study explored, whether and how carnosic acid induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to carnosic acid significantly increased the percentage of annexin-V-binding cells (2.5 µg/ml), significantly decreased forward scatter (10 µg/ml), significantly increased Fluo3 fluorescence (10 µg/ml), significantly increased ceramide abundance (10 µg/ml), significantly increased hemolysis (10 µg/ml), but significantly decreased DCFDA fluorescence (10 µg/ml). The effect of carnosic acid on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca²⁺. Conclusion: Carnosic acid triggers cell shrinkage and phospholipid scrambling of the human erythrocyte cell membrane, an effect paralleled by and/or in part due to Ca²⁺ entry and increased ceramide abundance.

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Carnosic acid suppresses colon tumor formation in association with antiadipogenic activity

Abstract: CA appears to alleviate adipocity-related acceleration of colon tumor formation.

Cited by 34 publications

References 46 publications

Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity

Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

Enhanced Eryptosis Following Exposure to Carnosic Acid

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