Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis

Bishayee, Anupam; Mandal, Animesh; Bhattacharyya, Piyali; Bhatia, Deepak

doi:10.1080/01635581.2016.1115094

Cited by 56 publications

(52 citation statements)

References 57 publications

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“…In this review paper, we clearly summarized significantly higher cancer risk reduction activity in natural phyto-complexes when compared to isolated molecules [1]. Finally, significant (in many cases robust) chemopreventive effectiveness of various plant whole foods (dark fruits, herbs) in mammary carcinogenesis in female rats has also been described by other authors [46][47][48][49]. The translation of data from animal studies (such as daily doses of plant foods suitable for humans or effective plasma levels of plant metabolites) to clinical practice is not easily applicable.…”

Section: Discussionmentioning

confidence: 68%

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

et al. 2020

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Comprehensive oncology research suggests an important role of phytochemicals or whole plant foods in the modulation of signaling pathways associated with anticancer action. The goal of this study is to assess the anticancer activities of Cinnamomum zeylanicum L. using rat, mouse, and cell line breast carcinoma models. C. zeylanicum (as bark powder) was administered in the diet at two concentrations of 0.1% (w/w) and 1% (w/w) during the whole experiment in chemically induced rat mammary carcinomas and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular evaluations of mammary gland tumors in rodents were carried out. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were performed. The dominant metabolites present in the tested C. zeylanicum essential oil (with relative content over 1%) were cinnamaldehyde, cinnamaldehyde dimethyl acetal, cinnamyl acetate, eugenol, linalool, eucalyptol, limonene, o-cymol, and α-terpineol. The natural mixture of mentioned molecules demonstrated significant anticancer effects in our study. In the mouse model, C. zeylanicum at a higher dose (1%) significantly decreased tumor volume by 44% when compared to controls. In addition, treated tumors showed a significant dose-dependent decrease in mitotic activity index by 29% (0.1%) and 45.5% (1%) in comparison with the control group. In rats, C. zeylanicum in both doses significantly reduced the tumor incidence by 15.5% and non-significantly suppressed tumor frequency by more than 30% when compared to controls. An evaluation of the mechanism of anticancer action using valid oncological markers showed several positive changes after treatment with C. zeylanicum. Histopathological analysis of treated rat tumor specimens showed a significant decrease in the ratio of high-/low-grade carcinomas compared to controls. In treated rat carcinomas, we found caspase-3 and Bax expression increase. On the other hand, we observed a decrease in Bcl-2, Ki67, VEGF, and CD24 expressions and MDA levels. Assessment of epigenetic changes in rat tumor cells in vivo showed a significant decrease in lysine methylation status of H3K4m3 and H3K9m3 in the high-dose treated group, a dose-dependent increase in H4K16ac levels (H4K20m3 was not changed), down-regulations of miR21 and miR155 in low-dose cinnamon groups (miR22 and miR34a were not modulated), and significant reduction of the methylation status of two out of five gene promoters—ATM and TIMP3 (PITX2, RASSF1, PTEN promoters were not changed). In vitro study confirmed results of animal studies, in that the essential oil of C. zeylanicum displayed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using MTS, BrdU, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). As a conclusion, C. zeylanicum L. showed chemopreventive and therapeutic activities in animal breast carcinoma models that were also significantly confirmed by mechanistic evaluations in vitro and in vivo.

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Section: Discussionmentioning

confidence: 68%

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

et al. 2020

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“…This observation is in accordance with several studies, which showed that DMBA alters the normal process of mammary gland differentiation. 18,36,46,47 Daucosterol reduced spleen, liver, lungs, and kidneys wet weights to the normal values compared to the DMBA group. These organs are indicators of toxicity when testing natural substances.…”

Section: T a B L Ementioning

confidence: 82%

Daucosterol from Crateva adansoniiDC (Capparaceae) reduces 7,12‐dimethylbenz(a)anthracene‐induced mammary tumors in Wistar rats

Nguedia

Tueche

Yaya

et al. 2020

Environmental Toxicology

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This study aimed to evaluate the in vivo anticancer effects of daucosterol which was earlier reported to possess in vitro anticancer effects. Breast tumor was induced in 30 rats using the environmental carcinogen 7,12‐dimethylbenz(a)anthracene (DMBA) while 6 control rats received olive oil (NOR). Animals with palpable tumors were randomized into five groups (n = 6) each as follows: negative control group treated with the vehicle (DMBA); positive control group treated with 5 mg/kg BW doxorubicin (DOXO + DMBA); three groups treated with daucosterol at doses of 2.5, 5, and 10 mg/kg BW (DAU + DMBA). Treatment lasted 28 days afterward, tumor (mass, volume, cancer antigen [CA] 15‐3 level and histoarchitecture), hematological and toxicological parameters were examined. The tumor volume gradually increased in the DMBA group during the 28 days, with a tumor volume gain of ∼390 cm3. Daucosterol at all doses reduced tumor volume (∼133.7 cm3 at 10 mg/kg) as well as protein, malondialdehyde (MDA), and CA 15‐3 levels compared to DMBA rats. Tumor sections in daucosterol‐treated rats showed a lower proliferation of mammary ducts with mild (5 and 10 mg/kg) to moderate (2.5 mg/kg) inflammatory responses. Moreover, it exhibited an antioxidant effect, evidenced by a significant and dose‐dependent decreased in MDA levels, as well as an increase in catalase activity compared to the DMBA group. Daucosterol showed for the first time in vivo antitumor effects that corroborate its previous in vitro effects.

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“…. There is abundant research in animal models that highlights a significant role of polyphenols and polyphenol‐rich plant extracts in the prevention of breast cancer, including resveratrol, ellagic acid, berries, pomegranate, and citrus flavanones . However, this evidence remains elusive in humans.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Profiling of Dietary Polyphenols and Methylxanthines in Normal and Malignant Mammary Tissues from Breast Cancer Patients

Ávila‐Gálvez

Garcı́a-Villalba

Martínez‐Díaz

et al. 2019

Molecular Nutrition Food Res

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Scope: Dietary polyphenols may protect against breast cancer. However, it is unknown whether polyphenols reach human malignant breast tumors in molecular forms and(or) at concentrations likely to act against cancer. Methods and Results: Ninteen breast cancer patients consumed three capsules daily from biopsy-confirmed diagnosis to surgery (6 ± 2 days). The capsules contained pomegranate, orange, lemon, olive, cocoa, and grapeseed extracts plus resveratrol, providing 37 different phenolics (473.7 mg), theobromine and caffeine (19.7 mg). A total of 101 metabolites are identified in urine, 69 in plasma, 39 in normal (NT), and 33 in malignant (MT) tissues by UPLC-ESI-QTOF-MS. Eight control patients did not consume extracts. Phenolic-derived metabolites in MT and NT are mainly glucuronidated and(or) sulfated. Some representative metabolites detected in MT (median and range, pmol g −1 ) are urolithin-A-3-O-glucuronide (26.2; 3.2−66.5), 2,5-dihydroxybenzoic acid (40. 2; 27.7−52.2), resveratrol-3-O-sulfate (86.4; 7.8−224.4), dihydroresveratrol-3-O-glucuronide (109.9; 10.3−229.4), and theobromine (715.0; 153.9−3,216). Metabolites, as detected in breast tissues, do not exert antiproliferative or estrogenic/antiestrogenic activities in MCF-7 breast cancer cells. Conclusion: This is the first study that describes the metabolic profiling of dietary phenolics and methylxanthines in MT and NT comprehensively. Although phase-II conjugation might hamper a direct anticancer activity, long-term tumor-senescent chemoprevention cannot be discarded.

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Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis

Cited by 56 publications

References 57 publications

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

Daucosterol from Crateva adansoniiDC (Capparaceae) reduces 7,12‐dimethylbenz(a)anthracene‐induced mammary tumors in Wistar rats

Metabolic Profiling of Dietary Polyphenols and Methylxanthines in Normal and Malignant Mammary Tissues from Breast Cancer Patients

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