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Oxidative Stress and Cancer: Chemopreventive and Therapeutic Role of Triphala.

ABSTRACT: Oxidative stress, caused by the overproduction of free radicals, leads to the development of many chronic diseases including cancer. Free radicals are known to damage cellular biomolecules like lipids, proteins, and DNA that results in activation of multiple signaling pathways, growth factors, transcription factors, kinases, inflammatory and cell cycle regulatory molecules. Antioxidants, which are classified as exogenous and endogenous, are responsible for the removal of free radicals and consequently the reduction in oxidative stress-mediated diseases. Diet and medicinal herbs are the major source of antioxidants. Triphala, which is a traditional Ayurvedic formulation that has been used for centuries, has been shown to have immense potential to boost antioxidant activity. It scavenges free radicals, restores antioxidant enzymes and non-enzyme levels, and decreases lipid peroxidation. In addition, Triphala is revered as a chemopreventive, chemotherapeutic, immunomodulatory, and radioprotective agent. Accumulated evidence has revealed that Triphala modulates multiple cell signaling pathways including, ERK, MAPK, NF-?B, Akt, c-Myc, VEGFR, mTOR, tubulin, p53, cyclin D1, anti-apoptotic and pro-apoptotic proteins. The present review focuses on the comprehensive appraisal of Triphala in oxidative stress and cancer.

SUBMITTER: Prasad S

PROVIDER: S-EPMC7022920 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Oxidative Stress and Cancer: Chemopreventive and Therapeutic Role of Triphala.

Prasad Sahdeo S Srivastava Sanjay K SK

Antioxidants (Basel, Switzerland) 20200113 1

Oxidative stress, caused by the overproduction of free radicals, leads to the development of many chronic diseases including cancer. Free radicals are known to damage cellular biomolecules like lipids, proteins, and DNA that results in activation of multiple signaling pathways, growth factors, transcription factors, kinases, inflammatory and cell cycle regulatory molecules. Antioxidants, which are classified as exogenous and endogenous, are responsible for the removal of free radicals and conseq ...[more]

PMID: 31941067

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Project description:Prevention and treatment of advanced prostate cancer (PCa) by a nontoxic agent can improve outcome, while maintaining quality of life. 4-methylumbelliferone (4-MU) is a dietary supplement that inhibits hyaluronic acid (HA) synthesis. We evaluated the chemopreventive and therapeutic efficacy and mechanism of action of 4-MU. TRAMP mice (7-28 per group) were gavaged with 4-MU (450mg/kg/day) in a stage-specific treatment design (8-28, 12-28, 22-28 weeks). Efficacy of 4-MU (200-450mg/kg/day) was also evaluated in the PC3-ML/Luc(+) intracardiac injection and DU145 subcutaneous models. PCa cells and tissues were analyzed for HA and Phosphoinositide 3-kinase (PI-3K)/Akt signaling and apoptosis effectors. HA add-back and myristoylated Akt (mAkt) overexpression studies evaluated the mechanism of action of 4-MU. Data were analyzed with one-way analysis of variance and unpaired t test or Tukey's multiple comparison test. All statistical tests were two-sided. While vehicle-treated transgenic adenocarcinoma of the prostate (TRAMP) mice developed prostate tumors and metastases at 28 weeks, both were abrogated in treatment groups, without serum/organ toxicity or weight loss; no tumors developed at one year, even after stopping the treatment at 28 weeks. 4-MU did not alter the transgene or neuroendocrine marker expression but downregulated HA levels. However, 4-MU decreased microvessel density and proliferative index (P < .0001,). 4-MU completely prevented/inhibited skeletal metastasis in the PC3-ML/Luc(+) model and DU145-tumor growth (85-90% inhibition, P = .002). 4-MU also statistically significantly downregulated HA receptors, PI-3K/CD44 complex and activity, Akt signaling, and β-catenin levels/activation, but upregulated GSK-3 function, E-cadherin, and apoptosis effectors (P < .001); HA addition or mAkt overexpression rescued these effects. 4-MU is an effective nontoxic, oral chemopreventive, and therapeutic agent that targets PCa development, growth, and metastasis by abrogating HA signaling.

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Oxidative Stress and Cancer: Chemopreventive and Therapeutic Role of Triphala.

Publications

Oxidative Stress and Cancer: Chemopreventive and Therapeutic Role of Triphala.

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