The combined effect of pomegranate extract and tangeretin on the DMBA-induced breast cancer model

Gül, Hüseyin Fatih; İlhan, Necip; Ozercan, İbrahim Hanifi; Kuloğlu, Tuncay

doi:10.1016/j.jnutbio.2020.108566

Cited by 21 publications

(9 citation statements)

References 47 publications

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“…e so-called phytoestrogens were reported to be able to compete with endogenous estrogens for binding estrogen receptors and to inhibit aromatase activity [51]. As recently suggested by Gul et al [44], phytoestrogenic molecules are capable of inhibiting estrogen activity (antagonistic effect against ER) or estrogen synthesis (inhibition of aromatase synthesis). e nonsignificant increase in serum levels of estradiol observed at the dose of 100 mg/kg indicates the ability of D. edulis to act in a tissue-specific way and to antagonize estrogen receptors in the mammary glands and breast tumors, thus reducing estradiol levels in these tissues, since estradiol is known to stimulate its biosynthesis in estrogen-sensitive tissues [50].…”

Section: Discussionmentioning

confidence: 98%

“…e exposition to environmental pollutants such as DMBA induced mutation, DNA damage, oncogene activation, and cancer genesis [40,41]. e administration of a single dose of DMBA (50-80 mg/kgBW) to female rats was reported to induce breast cancer development [21,[41][42][43][44]. In agreement with this report, our results showed that, after the subcutaneous administration of a single dose of DMBA (50 mg/kgBW) under the mammary gland of female Wistar rats, breast tumors developed 22-26 weeks later, with an induction percentage of 40%.…”

Section: Discussionmentioning

confidence: 99%

“…erefore, in addition to the ability of this environmental pollutant to stimulate steroidogenesis [46], DMBA may also promote the synthesis of the precursor of steroid hormones: cholesterol. e increase of estradiol levels would justify the increased invasion and density of cancer cells in breast tumors and the hypertrophy of breast lobules, taking into account the significant role of estrogens in the stimulation of cell proliferation [4,44].…”

Section: Discussionmentioning

confidence: 99%

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Aqueous Extract of Dacryodes edulis (Burseraceae) Leaves Inhibited Tumor Growth in Female Wistar Rats with 7,12-Dimethylbenz[a]anthracene-Induced Breast Cancer

Mvondo

Kamgaing

Ngnokam

2021

Evidence-Based Complementary and Alternative Medicine

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Breast cancer is the most common estrogen-dependent cancer in the world. Hormone therapy for this cancer can be neoadjuvant and/or adjuvant. Herbal remedies with antiproliferative properties are believed to be potential anticancer agents. The aqueous extract of Dacryodes edulis (Burseraceae) leaves (AE), a medicinal plant used against cancer in Cameroon, was found to display antiproliferative effects in ovariectomized rats. Compounds isolated from this plant exhibited anticancer activity in vitro. To determine whether AE has an anticancer potential, its effects were investigated in rats with already developed breast cancer. Mammary tumors were induced by a single subcutaneous administration (under the mammary gland) of 7,12-dimethylbenz[a]anthracene (DMBA; 50 mg/kgBW) to immature female rats. After 22–26 weeks of observation, animals with palpable tumors were treated with tamoxifen (3.3 mg/kgBW) and AE at doses of 25 and 100 mg/kgBW. The negative control received distilled water. Treatments were given orally for 21 consecutive days. The volume of mammary tumors was evaluated weekly using a caliper. On day 22, animals were sacrificed. Cholesterol and estradiol levels were assessed in serum, breast tumors, mammary glands, and ovaries. Oxidative status of tumors was evaluated. The histological analysis of mammary glands and breast tumors was performed. Results showed that AE reduced tumor volume and weight ( p < 0.05 ). This effect was associated with reduced cholesterol ( p < 0.001 ) and estradiol ( p < 0.01 ) levels in breast tumors, serum, ovaries, and mammary glands. AE also increased tumors levels of malondialdehyde ( p < 0.05 ) and antioxidant enzymes ( p < 0.01 ). These effects contributed to the decrease in the size of breast alveoli ( p < 0.01 ), the density of cancer cells in breast tumors, and the invasion of these cells into the tumor connective tissue. In conclusion, the aqueous extract of D. edulis leaves, thanks to its ability to inhibit tumor growth, could be considered as a potential alternative for the neoadjuvant treatment of estrogen-dependent breast cancer.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Aqueous Extract of Dacryodes edulis (Burseraceae) Leaves Inhibited Tumor Growth in Female Wistar Rats with 7,12-Dimethylbenz[a]anthracene-Induced Breast Cancer

Mvondo

Kamgaing

Ngnokam

2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…The inflammatory cytokines are the end product of the upstream signaling proteins such as NF-κB, which are inhibited by the IκB within the cytosol [59]. During inflammatory condition, the NF-κB becomes free from the inhibitory influence of the IκB and undergoes nuclear translocation to modulate the expression of concerned genes associated with the pro-inflammatory cytokines production [59]. Similarly, the body is armed with natural antioxidant defense mechanism such as Nrf/HO-1, which tends to neutralize the increased oxidative stress and protect the cellular environment from the oxidative stress mediated damage [60].…”

Section: Discussionmentioning

confidence: 99%

N‐(benzylidene)‐2‐((2‐hydroxynaphthalen‐1‐yl)diazenyl)benzohydrazides (1‐2) (NCHDH and NTHDH) attenuate DMBA‐induced breast cancer via Nrf2/NF‐κB/apoptosis signaling

Khan

Shal

et al. 2022

Fundamemntal Clinical Pharma

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The present study investigated the effect of the N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (1-2) (NCHDH and NTHDH) against breast cancer using in vitro and in vivo approaches. The NCHDH and NTHDH significantly inhibited the growth of the MCF-7 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The NCHDH and NTHDH treatment significantly inhibited the tumor size, tumor weight, and tumor volume, while it enhanced the survival and tumor free survival rate following 7,12-Dimethylbenz[a]anthracene (DMBA)induced breast cancer. The NCHDH and NTHDH markedly attenuated the oxidative stress markers and induced the antioxidant level. The enzymelinked immunosorbent assay (ELISA) showed significant reduction in the inflammatory cytokines production compared with the DMBA control. The NCHDH and NTHDH treatment significantly improved the histological features using hematoxylin and eosin (H and E) staining, Masson's trichrome, PAS (periodic acid Schiff), and Toluidine blue staining compared with the DMBA-induced group. The NCHDH and NTHDH treatment improved the hematological and serological parameters following DMBA-induced breast tumor compared with DMBA-induced group. Furthermore, the NCHDH and NTHDH treatment significantly enhanced the antioxidants signaling proteins such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase 1 (HO-1). The NCHDH and NTHDH enhanced the inhibitor of NF-κB (IκB) level, while it attenuated the NF-κB level. Similarly, the NCHDH and NTHDH showed marked increase in the apoptosis proteins such as Caspase-3, Caspase-9, and Bcl-2 Associated X-protein (Bax), while it inhibited the B-cell lymphoma 2 (Bcl-2) expression. In conclusion, the NCHDH and NTHDH significantly improved the DMBA-induced breast cancer via attenuating oxidative stress and inflammatory cytokines.

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Therapeutic effects of tilorone on mammary carcinogenesis through downregulation of pro‐inflammatory cytokines and oxidative stress

Chhipa,

Sharma,

Verma

et al. 2024

Drug Development Research

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Tilorone dihydrochloride (tilorone) is an orally active interferon inducer with anticancer effects. The present study aimed to evaluate the anticancer effects of tilorone in breast cancer. MTT assay was done to measure the proliferation of MCF‐7 and MDA‐MB‐231 breast cancer cells after treatment with tilorone. Mammary carcinogenesis was induced by subcutaneous injection (35 mg/kg, 0.5 mL) of dimethylbenz[a]anthracene (DMBA) in mammary pads of Sprague Dawley (SD) rats. Tumors were allowed to grow for 16 weeks till their sizes reached to 550–700 mm3, and then treated with 10 and 20 mg/kg of tilorone and standard drug doxorubicin (4 mg/kg) twice a week for 3 weeks. Normal and disease‐control animals received normal saline. Tumor volumes and body weights were measured. Tumors were isolated to measure the levels of interferon‐β (IFN‐β), vascular endothelial growth factor‐A (VEGF‐A), P53 and inflammatory markers by enzyme‐linked immunosorbent assay (ELISA). Serum biochemistry, lipid peroxidation (LPO) and antioxidant enzymes were measured by standard methods. Histopathology and immunohistochemistry (IHC) of P53 was done in tumor sections. Tilorone reduced the proliferation of MCF‐7 and MDA‐MB‐231 cells with IC50 concentrations at 34.08 µM and 14.27 µM, respectively. Tilorone treatment showed reduced tumor volume, and increased survival with no significant changes in the body weights. Tilorone treatment also decreased levels of inflammatory markers and VEGF‐A and increased IFN‐β and P53 levels. Further, treatment with tilorone also decreased LPO and increased antioxidants levels. Histopathology of tumor sections showed normalizing morphology of treated animals. IHC of tumor sections showed increased levels of P53. In conclusion, tilorone has potential anticancer effects against breast cancer.

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The combined effect of pomegranate extract and tangeretin on the DMBA-induced breast cancer model

Cited by 21 publications

References 47 publications

Aqueous Extract of Dacryodes edulis (Burseraceae) Leaves Inhibited Tumor Growth in Female Wistar Rats with 7,12-Dimethylbenz[a]anthracene-Induced Breast Cancer

Aqueous Extract of Dacryodes edulis (Burseraceae) Leaves Inhibited Tumor Growth in Female Wistar Rats with 7,12-Dimethylbenz[a]anthracene-Induced Breast Cancer

N‐(benzylidene)‐2‐((2‐hydroxynaphthalen‐1‐yl)diazenyl)benzohydrazides (1‐2) (NCHDH and NTHDH) attenuate DMBA‐induced breast cancer via Nrf2/NF‐κB/apoptosis signaling

Therapeutic effects of tilorone on mammary carcinogenesis through downregulation of pro‐inflammatory cytokines and oxidative stress

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