The Flavonol Isorhamnetin Exhibits Cytotoxic Effects on Human Colon Cancer Cells

Jaramillo, Sara; López, Sergio; Varela, Lourdes M.; Rodríguez-Arcos, Rocío; Jiménez, Ana; Abia, Rocı́o; Guillén, Rafael; Muriana, Francisco J.G.

doi:10.1021/jf102669p

Cited by 102 publications

(82 citation statements)

References 32 publications

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“…Ramachandran 22 found that Iso inhibited the migratory/invasive properties of gastric cancer cells through modulation of the PPAR-γ activation pathway. Jaramillo 23 found that Isoinhibtied colon cancer cells growth by interrupting cell cycle progression. Iso is also found to promote lung cancer cell apoptosis through mitochondriadependent caspase activation in vitro and vivo 24 .…”

Section: +mentioning

confidence: 99%

Commentary: Protective Effects of Isorhamnetin on N2a Cell Against Endoplasmic Reticulum Stress-induced Injury Is Mediated by PKC?

Lu¹

2017

J Neurol Neuromedicine

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Neuronal apoptosis is an important pathophysiological factor of Alzheimer's disease (AD). Inhibition of endoplasmic reticulum stress (ERS)-induced neuronal apoptosis is an effective strategy to deal with AD. In this commentary, we summarize the relationship between AD and ERS injury-induced neuronal apoptosis, and highlight the protective effects and mechanism of isorhamnetin (Iso) against ERS-induced injury in N2a cells. Moreover, this commentary discusses the recent findings in the role of Iso in other diseases.Alzheimer's disease (AD) is a chronic neurodegenerative disease, and the fourth leading cause of death, behind heart disease, cancer and stroke 1. The clinical manifestations of AD include deteriorating cognitive function and memory, a decline in functioning in daily life activities, anda variety of neuropsychiatric symptoms and behavioral disorders 2,3 . The risk of AD gradually increases with age. There are more than 30 million AD patient living in the world today 4,5 .The etiology and pathogenesis of AD is not clear. AD is characterized by the accumulation of misfolded β-amyloid proteins caused by various genetic and environmental factors. These Aβ-plaques are associated with several pathological changes including the aggregation of misfolded proteins, formation of tissue precipitation, intracellular calcium disturbance, DNA fragmentation and lipid peroxidation. Together, these factors induce neuronal apoptosis and necrosis 6 . Thus, inhibiting neuron apoptosis is an effective way to prevent AD.The endoplasmic reticulum (ER) is theprincipal organelle for protein synthesis, protein folding and maintenance of calcium homeostasis 7 . Numerous stimuli, such as hypoxia and oxidative stress, can perturb calcium balance, and promote accumulation of unfolded and misfolded proteins in the ER lumen. This is known as endoplasmic reticulum stress (ERS) 8 . ERS is one of the key drivers of apoptosis. ERS induces apoptosis, through activation of the ASK and p38 MAPK signal pathway, trigger the kinase function of IRE1 [9][10][11] . Additionally, p38MAPK is reported to promote phosphorylation and activation of pro-apoptotic protein Bax 12,13 . Recent studies suggest that AD pathology is associated with ERS 14 . ERS generates a toxic environment in neurons, which in turn activates endoplasmic reticulum pathways that ultimately cause apoptosis 15 . Thus, inhibition of ERS injury may be an effective strategy to prevent AD.

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Section: +mentioning

confidence: 99%

Commentary: Protective Effects of Isorhamnetin on N2a Cell Against Endoplasmic Reticulum Stress-induced Injury Is Mediated by PKC?

Lu¹

2017

J Neurol Neuromedicine

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“…1,22 LoVo cells (1 · 10 6 ) were seeded in 6sixwell flat-bottomed plates, grown overnight until they reached 80% confluence, and then treated with vehicle alone (0.1% DMSO) or with PNSE (0, 100, or 500 lg/mL) for 48 h. After treatment, the detached cells in the medium were collected and combined with the remaining adherent cells that were detached by brief trypsinization (0.25% trypsin-EDTA, Sigma-Aldrich). Cell pellets were fixed in 70% ethanol, washed in PBS, resuspended in 1.0 mL of PBS containing 1.0 mg/mL RNase and 50 lg/mL PI, incubated in the dark for 30 min at room temperature, and analyzed with a GUAVA Ò easyCyteÔ 8HT flow cytometer (Millipore).…”

Section: Cell Cycle Analysis Using Flow Cytometrymentioning

confidence: 99%

“…1,16,17 DMSO was used as the vehicle to deliver PNSE, and the final concentration of DMSO in all experiments was 0.1%. All experiments were done independently in triplicate per experimental point.…”

Section: Cell Culturementioning

confidence: 99%

“…After 24 h (the cells were grown to 90% confluence), the cells were treated with serial concentrations (0, 100, 250, and 500 lg/mL) of PNSE in 1% DMSO for various periods of time (24 and 48 h). The final concentration of DMSO in culture medium was maintained at 0.1%, 1,20 and fluorouracil (5-Fu) (250 lg/mL) was used as a positive control. After the exposure period, 10 lL of MTT (5 mg/mL) in phosphate-buffered saline (PBS) solution was added to each well at a final concentration of 0.5 mg/mL, and then the plate was further incubated for 4 h. MTTcontaining media were removed, and 100 lL of a solution containing 10% sodium dodecyl sulfate (pH 4.8) plus 0.01 M HCl and 5% isobutyl alcohol was added to each well and mixed thoroughly to dissolve the formed crystal formazan.…”

Section: Analysis Of Cell Viabilitymentioning

confidence: 99%

“…1 It is also widely recognized that colon cancer is the third most common cancer in men (after lung and prostate cancers) and is the second to breast cancer in women. 2 It is interesting that only 5-10% of the cases are due to genetic factors, whereas more than 70% are related to diet and lifestyle, suggesting that colon cancer rates could be substantially reduced by changes in dietary and lifestyle patterns.…”

Section: Introduction Cmentioning

confidence: 99%

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Antioxidant, Antiproliferative, and Pro-Apoptotic Activities of a Saponin Extract Derived from the Roots of Panax notoginseng (Burk.) F.H. Chen

Zhao

Guo

et al. 2012

Journal of Medicinal Food

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Dietary and medicinal uses of Panax notoginseng have been associated with reduced risk of cancer. This study was designed to investigate the profiles of P. notoginseng saponin extract (PNSE), the major bioactive ingredients in P. notoginseng (Burk.) F.H. Chen, by high-performance liquid chromatography, and, for the first time, the anticancer effect of PNSE in the human colon cancer cell line LoVo was further evaluated. The major saponins present in PNSE were ginsenosides Rg1 (31.1%) and Rb1 (34.4%), and the total content of the eight saponins identified (notoginsenoside R1, ginsenosides Rg1, Re, Rb1, Rc, and Rd, and isomeric ginsenosides Rb2 and Rb3) was 81.7%, indicating that it was a highly purified standardized saponin extract. Furthermore, PNSE was found to have a markedly cytotoxic effect and antiproliferative activity against the LoVo cell line in a dose-and time-dependent manner. Flow cytometry analysis demonstrated that PNSE caused cell cycle arrest at S phase. Moreover, PNSE was found to possess antioxidative capacities in the 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay and hydroxyl radical scavenging assay in vitro. Taken together, the present results suggest that naturally occurring PNSE may provide significant natural defense against human colon cancer.KEY WORDS: antioxidant activity antitumor activity ginsenoside high-performance liquid chromatography notoginsenoside Panax notoginseng

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Targeting colorectal cancer using dietary flavonols

Dubey,

Bhadoria

et al. 2023

Cancer Innovation

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Colorectal cancer is among the well‐known forms of cancer and a prominent cause of cancer demises worldwide. In vitro experiments reinforced by animal studies, as well as epidemiological studies of human colorectal cancer propose that the growth of this disease can be moderated by eating aspects. Dietary intake including green vegetables and fruits may result in the reduction of colon cancer chances. The finding suggests that the combinations of dietary nutrients may deliver additive or synergistic effects and might be a powerful method to avoid or eradicate colon cancer beginning and/or development. Flavonols are one of the most widespread dietary nutrients of the polyphenols‐flavonoids and major constituent of Allium and Brassicaceae vegetables. Flavonols present in vegetables of Allium and Brassicaceae family are kaempferol, myricetin, quercetin, and isorhamnetin. These flavonols are claimed to have antiproliferative activity in vivo and in vitro against colorectal cancer. The objective of this review is to summarize the role of flavonols obtained from dietary sources in the prevention and treatment of colorectal cancer.

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The Flavonol Isorhamnetin Exhibits Cytotoxic Effects on Human Colon Cancer Cells

Cited by 102 publications

References 32 publications

Commentary: Protective Effects of Isorhamnetin on N2a Cell Against Endoplasmic Reticulum Stress-induced Injury Is Mediated by PKC?

Commentary: Protective Effects of Isorhamnetin on N2a Cell Against Endoplasmic Reticulum Stress-induced Injury Is Mediated by PKC?

Antioxidant, Antiproliferative, and Pro-Apoptotic Activities of a Saponin Extract Derived from the Roots of Panax notoginseng (Burk.) F.H. Chen

Targeting colorectal cancer using dietary flavonols

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