Morin and Esculetin supplementation modulates c-myc induced energy metabolism and attenuates neoplastic changes in rats challenged with the procarcinogen 1,2 - dimethylhydrazine

Sharma, Sharada H.; Thulasingam, Senthilkumar; Chellappan, David Raj; Chinnaswamy, Prabu; Sangeetha, N.

doi:10.1016/j.ejphar.2016.12.019

Cited by 37 publications

(30 citation statements)

References 45 publications

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“…We then tested the effect of morin in cancerous cells resistant to apoptosis, finding that, upon treatment with morin, apoptosis induced by 5‐FU is restored. These data are in agreement with previous studies reporting anticancer effects of morin in various cancer cell lines (melanoma, hepatoma, prostate cancer, HeLa cells) with mechanisms involving an increase of apoptosis …”

Section: Discussionsupporting

confidence: 93%

“…These data are in agreement with previous studies reporting anticancer effects of morin in various cancer cell lines (melanoma, hepatoma, prostate cancer, HeLa cells) with mechanisms involving an increase of apoptosis. [34][35][36][37][38] Based on these strong effects of morin in CRC cells in vitro, we then tested whether morin could restore the apoptotic response in Pirc We also show that morin, administered for 6 weeks to Pirc rats, decreases the number of preneoplastic MDF in the colon. This result is in agreement with reports showing that morin, (administered at the same dosage of the present study) may decrease colon carcinogenesis when given chronically (up to 30 weeks of treatment) to carcinogen-initiated rats.…”

Section: Discussionmentioning

confidence: 98%

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Morin‐dependent inhibition of low molecular weight protein tyrosine phosphatase (LMW‐PTP) restores sensitivity to apoptosis during colon carcinogenesis: Studies in vitro and in vivo, in an Apc‐driven model of colon cancer

Lori

Paoli²,

Femia

et al. 2019

Molecular Carcinogenesis

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LMW‐PTP has been associated with the development of colorectal cancer (CRC) and with the resistance to chemotherapy in cancer cells. To clarify its role in vivo, we studied LMW‐PTP expression in Pirc rats (F344/NTac‐Apc am1137), genetically prone to CRC and resistant to apoptosis. In the morphologically normal mucosa (NM) of Pirc rats, a dramatic over‐expression of LMW‐PTP was found compared to wt rats (about 60 times higher). Moreover, LMW‐PTP levels further increase in spontaneously developed Pirc colon tumors. To understand if and how LMW‐PTP affects resistance to apoptosis, we studied CRC cell lines, sensitive (HT29 and HCT‐116), or resistant (HT29R, HCT116R) to 5‐Fluorouracil (5‐FU): resistant cells over‐express LMW‐PTP. When resistant cells were challenged with morin, a polyphenol inhibiting LMW‐PTP, a fast and dose‐related down‐regulation of LMW‐PTP was observed. 5‐FU and morin co‐treatment dramatically decreased cell viability, increased apoptosis, and significantly impaired self‐renewal ability of all the cancer cell lines we have studied. Similarly, we observed that, in Pirc rats, one‐week morin administration (50 mg/kg) down‐regulated LMW‐PTP and restored the apoptotic response to 5‐FU in the NM. Finally, administration of morin for a longer period led to a significant reduction in colon precancerous lesions, together with a down‐regulation of LMW‐PTP. Taken together, these results document the involvement of LMW‐PTP in the process of CRC in vitro and in vivo. Morin treatment may be envisaged as a system to increase the sensitivity to chemotherapy and to prevent carcinogenesis.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Morin‐dependent inhibition of low molecular weight protein tyrosine phosphatase (LMW‐PTP) restores sensitivity to apoptosis during colon carcinogenesis: Studies in vitro and in vivo, in an Apc‐driven model of colon cancer

Lori

Paoli²,

Femia

et al. 2019

Molecular Carcinogenesis

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“…Esculetin has been widely used in antitussive aspects [150], and the study of Liang et al has demonstrated its protective effect against oxidative stress-induced DNA damage [151]. In addition, esculetin possesses anti-inflammatory [152,153], antibacterial [154,155], and antitumor activities against different cancer cells in vitro [156][157][158] and in vivo [159,160]. It has also been reported to enhance the inhibitory effect of 5-fluorouracil on the proliferation of colorectal cancer [161].…”

Section: Urolithin Amentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

164

106

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The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.

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“…Scientists have proposed that targeting the Warburg effect may be a new therapeutic anticancer strategy [245]. Many bitter phytochemicals (e.g., morin, scutellarein, naringenin, quercetin, and hesperetin) showed the capacity to counteract Warburg effect, by induction of a metabolic reprogramming of cancer cells, through downregulation of glucose transporter 1 (GLUT1) and inhibition of glycolysis (via hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A), leading eventually to apoptosis [246–251]. All these effects may be included under vishagna activity, which is assigned to bitter tasting medicinal plants or food in Ayurveda.…”

Section: Traditional Taste (Rasa) In the Light Of Modern Sciencementioning

confidence: 99%

Extraoral Taste Receptor Discovery: New Light on Ayurvedic Pharmacology

Gîlcă

Dragoș

2017

Evidence-Based Complementary and Alternative Medicine

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More and more research studies are revealing unexpectedly important roles of taste for health and pathogenesis of various diseases. Only recently it has been shown that taste receptors have many extraoral locations (e.g., stomach, intestines, liver, pancreas, respiratory system, heart, brain, kidney, urinary bladder, pancreas, adipose tissue, testis, and ovary), being part of a large diffuse chemosensory system. The functional implications of these taste receptors widely dispersed in various organs or tissues shed a new light on several concepts used in ayurvedic pharmacology (dravyaguna vijnana), such as taste (rasa), postdigestive effect (vipaka), qualities (guna), and energetic nature (virya). This review summarizes the significance of extraoral taste receptors and transient receptor potential (TRP) channels for ayurvedic pharmacology, as well as the biological activities of various types of phytochemical tastants from an ayurvedic perspective. The relative importance of taste (rasa), postdigestive effect (vipaka), and energetic nature (virya) as ethnopharmacological descriptors within Ayurveda boundaries will also be discussed.

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Morin and Esculetin supplementation modulates c-myc induced energy metabolism and attenuates neoplastic changes in rats challenged with the procarcinogen 1,2 - dimethylhydrazine

Cited by 37 publications

References 45 publications

Morin‐dependent inhibition of low molecular weight protein tyrosine phosphatase (LMW‐PTP) restores sensitivity to apoptosis during colon carcinogenesis: Studies in vitro and in vivo, in an Apc‐driven model of colon cancer

Morin‐dependent inhibition of low molecular weight protein tyrosine phosphatase (LMW‐PTP) restores sensitivity to apoptosis during colon carcinogenesis: Studies in vitro and in vivo, in an Apc‐driven model of colon cancer

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Extraoral Taste Receptor Discovery: New Light on Ayurvedic Pharmacology

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