Gossypol decreased cell viability and down-regulated the expression of a number of genes in human colon cancer cells

AbstractPlant polyphenol gossypol has anticancer activities. This may increase cottonseed value by using gossypol as a health intervention agent. It is necessary to understand its molecular mechanisms before human consumption. The aim was to uncover the effects of gossypol on cell viability and gene expression in cancer cells. In this study, human colon cancer cells (COLO 225) were treated with gossypol. MTT assay showed significant inhibitory effect under high concentration and longtime treatment. We analyzed the expression of 55 genes at the mRNA level in the cells; many of them are regulated by gossypol or ZFP36/TTP in cancer cells. BCL2 mRNA was the most stable among the 55 mRNAs analyzed in human colon cancer cells. GAPDH and RPL32 mRNAs were not good qPCR references for the colon cancer cells. Gossypol decreased the mRNA levels of DGAT, GLUT, TTP, IL families and a number of previously reported genes. In particular, gossypol suppressed the expression of genes coding for CLAUDIN1, ELK1, FAS, GAPDH, IL2, IL8 and ZFAND5 mRNAs, but enhanced the expression of the gene coding for GLUT3 mRNA. The results showed that gossypol inhibited cell survival with decreased expression of a number of genes in the colon cancer cells.

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Gossypol decreased cell viability and down-regulated the expression of a number of genes in human colon cancer cells

10.1021/scimeetings.1c00745 ◽

2021 ◽

Author(s):

Heping Cao ◽

kandan Sethumadhavan ◽

Fangping Cao ◽

Thomas Wang

Keyword(s):

Colon Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Number Of Genes ◽

Human Colon Cancer Cells

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Enhanced 4-Hydroxynonenal Resistance inKEAP1Silenced Human Colon Cancer Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/423965 ◽

2013 ◽

Vol 2013 ◽

pp. 1-16 ◽

Cited By ~ 12

Author(s):

Kyeong-Ah Jung ◽

Mi-Kyoung Kwak

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Target Gene ◽

Human Colon ◽

Adduct Formation ◽

Mrna Levels ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Ht29 Cells ◽

Human Colon Cancer Cells

Nuclear factor erythroid 2-related factor 2 (NRF2) is the transcription factor that regulates an array of antioxidant/detoxifying genes for cellular defense. The conformational changes of Kelch-like ECH-associated protein 1 (KEAP1), a cytosolic repressor protein of NRF2, by various stimuli result in NRF2 liberation and accumulation in the nucleus. In the present study, we aimed to investigate the effect ofKEAP1knockdown on NRF2 target gene expression and its toxicological implication using human colon cancer cells. The stableKEAP1-knockdown HT29 cells exhibit elevated levels of NRF2 and its target gene expressions. In particular, the mRNA levels of aldo-keto reductases (AKR1C1, 1C2, 1C3, 1B1, and 1B10) were substantially increased inKEAP1silenced HT29 cells. These differential AKRs expressions appear to contribute to protection against oxidative stress. TheKEAP1-knockdown cells were relatively more resistant to hydrogen peroxide (H2O2) and 4-hydroxynonenal (4HNE) compared to the control cells. Accordantly, we observed accumulation of 4HNE protein adducts in H2O2- or 4HNE-treated control cells, whereasKEAP1-knockdown cells did not increase adduct formation. The treatment ofKEAP1-silenced cells with AKR1C inhibitor flufenamic acid increased 4HNE-induced cellular toxicity and protein adduct formation. Taken together, these results indicate that AKRs, which are NRF2-dependent highly inducible gene clusters, play a role in NRF2-mediated cytoprotection against lipid peroxide toxicity.

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