<i>Azadirachta indica</i> acts as a pro‐oxidant and modulates cell cycle associated proteins during DMBA/TPA induced skin carcinogenesis in mice

Arora, Neha; Bansal, M. P.; Koul, Ashwani

doi:10.1002/cbf.2909

Cited by 20 publications

(15 citation statements)

References 57 publications

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“…[ 49 ] The increase in LPO levels in the Silibinin+DMBA/TPA group is associated with a decrease in the GSH content which is consistent with previous observations from our laboratory. [ 10 ]…”

Section: Discussionmentioning

confidence: 99%

“…indica in tumors has also been observed from our laboratory and others. [ 8 , 10 , 50 ] However, it has also been reported [ 46 ] that topical administration of Silibinin hinders cutaneous lipid peroxidation. This antagonist behavior of Silibinin could be due to the difference in the mode of administration of the drug, due to which its absorption into the systemic circulation is affected.…”

Section: Discussionmentioning

confidence: 99%

“…[ 7 ] In addition to the antioxidant action of chemopreventive compounds, their pro-oxidant action in certain conditions has also been proposed to be imperative for their anti-cancer potential. [ 8 – 10 ] The pro-oxidant action of chemopreventive compounds through generation of ROS causes oxidative damage, membrane dysfunction, mitochondrial toxicity, and apoptotic DNA fragmentation. [ 11 ]…”

Section: Introductionmentioning

confidence: 99%

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Pro-Oxidant Role of Silibinin in DMBA/TPA Induced Skin Cancer: 1H NMR Metabolomic and Biochemical Study

et al. 2016

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Silibinin, a major bioactive flavonolignan in Silybum marianum, has received considerable attention in view of its anticarcinogenic activity. The present study examines its anticancer potential against 7, 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin cancer. Male LACA mice were randomly segregated into 4 groups: Control, DMBA/TPA, Silibinin and Silibinin+DMBA/TPA. Tumors in DMBA/TPA and Silibinin+DMBA/TPA groups were histologically graded as squamous cell carcinoma. In the Silibinin+DMBA/TPA group, significant reduction in tumor incidence (23%), tumor volume (64.4%), and tumor burden (84.8%) was observed when compared to the DMBA/TPA group. The underlying protective mechanism of Silibinin action was studied at pre-initiation (2 weeks), post-initiation (10 weeks) and promotion (22 weeks) stages of the skin carcinogenesis. The antioxidant nature of Silibinin was evident at the end of 2 weeks of its treatment. However, towards the end of 10 and 22 weeks, elevated lipid peroxidation (LPO) levels indicate the pro-oxidative nature of Silibinin in the cancerous tissue. TUNEL assay revealed enhanced apoptosis in the Silibinin+DMBA/TPA group with respect to the DMBA/TPA group. Therefore, it may be suggested that raised LPO could be responsible for triggering apoptosis in the Silibinin+DMBA/TPA group. 1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the metabolic profile of the skin /skin tumors. Dimethylamine (DMA), glycerophosphocholine (GPC), glucose, lactic acid, taurine and guanine were identified as the major contributors for separation between the groups from the Principal Component Analysis (PCA) of the metabolite data. Enhanced DMA levels with no alteration in GPC, glucose and lactate levels reflect altered choline metabolism with no marked Warburg effect in skin tumors. However, elevated guanine levels with potent suppression of taurine and glucose levels in the Silibinin+DMBA/TPA group are suggestive of the pro-oxidative nature of Silibinin in regressing tumors. Thus, supporting the theory of augmented LPO levels resulting in increased apoptosis in the skin tumors treated with Silibinin.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pro-Oxidant Role of Silibinin in DMBA/TPA Induced Skin Cancer: 1H NMR Metabolomic and Biochemical Study

et al. 2016

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“…18,19,[21][22][23][24][25][26]31,33 DMBA/TPA-induced papillomas typically exhibit enhanced activation of the cyclin D1 promoter as a result of the antagonism of NFκB signaling by Cyld 25 and show elevated expression of proliferation markers such as proliferating cell nuclear antigen and Ki-67. 34 Therefore, the increased sensitivity for skin tumors in FA(−) offspring in our study could be induced by the activation of NFκB signaling associated with the Cyld downregulation related to in utero FA shortage. Moreover, the diminished Cyld expression and activity were induced by DNA methylation of the SRE in the Cyld promoter region, although it remains possible that another CpG site in the promoter region also contributes to maternal FA-related regulation of Cyld.…”

Section: Similar Studiesmentioning

confidence: 69%

Maternal folic acid depletion during early pregnancy increases sensitivity to squamous tumor formation in the offspring in mice

Kawakubo‐Yasukochi

Morioka

Ohe

et al. 2019

J Dev Orig Health Dis

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Gestational nutrition is widely recognized to affect an offspring’s future risk of lifestyle-related diseases, suggesting the involvement of epigenetic mechanisms. As folic acid (FA) is a nutrient essential for modulating DNA methylation, we sought to determine how maternal FA intake during early pregnancy might influence tumor sensitivity in an offspring. Dams were maintained on a FA-depleted (FA(−)) or normal (2 mg FA/kg; FA(+)) diet from 2 to 3 days before mating to 7 days post-conception, and their offspring were challenged with chemical tumorigenesis using 7,12-dimethylbenz[a)anthracene and phorbol 12-myristate 13-acetate for skin and 4-nitroquinoline N-oxide for tongue. In both squamous tissues, tumorigenesis was more progressive in the offspring from FA(−) than FA(+) dams. Notably, in the skin of FA(−) offspring, the expression and activity of cylindromatosis (Cyld) were decreased due to the altered DNA methylation status in its promoter region, which contributed to increased tumorigenesis coupled with inflammation in the FA(−) offspring. Thus, we conclude that maternal FA insufficiency during early pregnancy is able to promote neoplasm progression in the offspring through modulating DNA methylation, such as Cyld. Moreover, we propose, for the first time, “innate” utero nutrition as the third cause of tumorigenesis besides the known causes—hereditary predisposition and acquired environmental factors.

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“…Also, cell cycle regulatory proteins may be modulated by AAILE and could affect the progression of cells through the cell cycle. [19]…”

Section: Herbal Drugs For Skin Diseasesmentioning

confidence: 99%

Plants used to treat skin diseases

Tabassum¹,

Hamdani²

2014

Phcog Rev

201

108

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Skin diseases are numerous and a frequently occurring health problem affecting all ages from the neonates to the elderly and cause harm in number of ways. Maintaining healthy skin is important for a healthy body. Many people may develop skin diseases that affect the skin, including cancer, herpes and cellulitis. Some wild plants and their parts are frequently used to treat these diseases. The use of plants is as old as the mankind. Natural treatment is cheap and claimed to be safe. It is also suitable raw material for production of new synthetic agents. A review of some plants for the treatment of skin diseases is provided that summarizes the recent technical advancements that have taken place in this area during the past 17 years.

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Azadirachta indica acts as a pro‐oxidant and modulates cell cycle associated proteins during DMBA/TPA induced skin carcinogenesis in mice

Cited by 20 publications

References 57 publications

Pro-Oxidant Role of Silibinin in DMBA/TPA Induced Skin Cancer: 1H NMR Metabolomic and Biochemical Study

Pro-Oxidant Role of Silibinin in DMBA/TPA Induced Skin Cancer: 1H NMR Metabolomic and Biochemical Study

Maternal folic acid depletion during early pregnancy increases sensitivity to squamous tumor formation in the offspring in mice

Plants used to treat skin diseases

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