SODIUM BUTYRATE EXERTS AN ANTI-COLORECTAL CANCER ACTION BY INDUCING FERRITINOPHAGE IN HCT-116 CELLS

LIU Lu-lin, HE Hua-xing, LIU Ying-yin, QIN Yong, SUN Xiao-die, SUN Su-xia

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (3) : 241-247.

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (3) : 241-247.
ORIGINAL ARTICLES

SODIUM BUTYRATE EXERTS AN ANTI-COLORECTAL CANCER ACTION BY INDUCING FERRITINOPHAGE IN HCT-116 CELLS

  • LIU Lu-lin, HE Hua-xing, LIU Ying-yin, QIN Yong, SUN Xiao-die, SUN Su-xia
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Abstract

Objective To investigate whether sodium butyrate (NaB) can exert its anti-colorectal cancer action by inducing ferritinophagy. Methods The effects of NaB on the proliferation and death of colorectal cancer HCT-116 cells were investigated using MTT assay, plate cloning assay, and PI staining. The induction of ferritinophagy in HCT-116 cells by NaB was explored through the use of autophagy detection kit (MDC method), ferrous ion fluorescent probe FerroOrange. Western blot analysis was performed to detect the expression of p62, FTH1, LC3 and NCOA4 molecules. Results The results of the MTT and colony formation experiments showed that 2 mmol/L NaB significantly inhibited the viability (P<0.001) and clone formation (P<0.01) of HCT-116 cells. The PI staining results showed that NaB increased the number of dead cells, and the iron chelator deferoxamine (DFO) reversed the inhibitory and pro-apoptotic effects of NaB on HCT-116 cells (P<0.05). The autophagy inhibitor chloroquine (CQ) further enhanced the inhibitory effect of NaB on HCT-116 cells (P<0.001). The results of MDC method and FerroOrange detection showed that NaB increased the formation of autophagic vacuoles and intracellular Fe2+ levels in HCT-116 cells (P<0.001). The upregulation of intracellular Fe2+ levels by NaB was reversed by DFO and CQ (P<0.05). Western blot analysis revealed that NaB downregulated the protein expression levels of p62 and FTH1 (P<0.001) and upregulated the protein expression levels of LC3-II, NCOA4 in HCT-116 cells (P<0.001, P<0.05). The downregulation of FTH1 protein expression level by NaB was reversed by CQ (P<0.05). Conclusion NaB can exert an anti-colorectal cancer action by inducing ferritinophagy in HCT-116 cells.

Key words

sodium butyrate / colorectal cancer / ferritinophagy

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LIU Lu-lin, HE Hua-xing, LIU Ying-yin, QIN Yong, SUN Xiao-die, SUN Su-xia. SODIUM BUTYRATE EXERTS AN ANTI-COLORECTAL CANCER ACTION BY INDUCING FERRITINOPHAGE IN HCT-116 CELLS[J]. Acta Nutrimenta Sinica. 2024, 46(3): 241-247

References

[1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74: 229-263.
[2] Reynolds A, Mann J, Cummings J, et al. Carbohydrate quality and human health: a series of systematic reviews and meta-analyses[J]. Lancet, 2019,393:434–445.
[3] McNabney SM, Henagan TM. Short chain fatty acids in the colon and peripheral tissues: a focus on butyrate, colon cancer, obesity and insulin resistance[J]. Nutrients, 2017,9:1348.
[4] Chen J, Vitetta L.Inflammation-modulating effect of butyrate in the prevention of colon cancer by dietary fiber[J]. Clin Colorectal Cancer, 2018,17:e541–e544.
[5] Pérez-Hernández M, Arias A, Martínez-García D, et al. Targeting autophagy for cancer treatment and tumor chemosensitization[J]. Cancers (Basel), 2019,11:1599.
[6] Bai Y, Meng L, Han L, et al. Lipid storage and lipophagy regulates ferroptosis[J]. Biochem Biophys Res Commun, 2019,508:997–1003.
[7] Mancias JD, Wang X, Gygi SP, et al. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy[J]. Nature, 2014,509:105–109.
[8] Rochette L, Dogon G, Rigal E, et al. Lipid peroxidation and iron metabolism: two corner stones in the homeo-stasis control of ferroptosis[J]. Int J Mol Sci, 2022,24:449.
[9] Hou W, Xie Y, Song X, et al. Autophagy promotes ferroptosis by degradation of ferritin[J]. Autophagy, 2016,12:1425–1428.
[10] Wei S, Qiu T, Yao X, et al. Arsenic induces pancreatic dysfunction and ferroptosis via mitochondrial ROS-autophagy-lysosomal pathway[J]. J Hazard Mater, 2020,384:121390.
[11] Lichtenstern CR, Ngu RK, Shalapour S, et al. Immuno-therapy, inflammation and colorectal cancer[J]. Cells, 2020,9:618.
[12] Jiang X, Overholtzer M, Thompson CB.Autophagy in cellular metabolism and cancer[J]. J Clin Invest, 2015,125:47–54.
[13] Hirano S, Uemura T, Annoh H, et al. Differing susceptibility to autophagic degradation of two LC3-binding proteins: SQSTM1/p62 and TBC1D25/OATL1[J]. Autophagy, 2016,12:312–26.
[14] Liu Y, Levine B.Autosis and autophagic cell death: the dark side of autophagy[J]. Cell Death Differ, 2015,22:367–376.
[15] Zhang Y, Zhang L, Gao J, et al. Pro-death or pro-survival: contrasting paradigms on nanomaterial-induced autophagy and exploitations for cancer therapy[J]. Acc Chem Res, 2019,52:3164–3176.
[16] Qi X, Zhang Y, Guo H, et al. Mechanism and intervention measures of iron side effects on the intestine[J]. Crit Rev Food Sci Nutr, 2020,60:2113–2125.
[17] Lee YS, Lee DH, Choudry HA, et al. Ferroptosis-induced endoplasmic reticulum stress: cross-talk between ferroptosis and apoptosis[J]. Mol Cancer Res, 2018,16:1073–1076.
[18] Holden P, Nair LS.Deferoxamine: An angiogenic and antioxidant molecule for tissue regeneration[J]. Tissue Eng Part B Rev, 2019,25:461–470.
[19] Tsai Y, Xia C, Sun Z.The inhibitory effect of 6-gingerol on ubiquitin-specific peptidase 14 enhances autophagy-dependent ferroptosis and anti-tumor in vivo and in vitro[J]. Front Pharmacol, 2020,11:598555.
[20] Yang ND, Tan SH, Ng S, et al. Artesunate induces cell death in human cancer cells via enhancing lysosomal function and lysosomal degradation of ferritin[J]. J Biol Chem, 2014,289:33425–33441.
[21] Xiu Z, Zhu Y, Han J, et al. Caryophyllene oxide induces ferritinophagy by regulating the NCOA4/FTH1/LC3 pathway in hepatocellular carcinoma[J]. Front Pharmacol, 2022,13:930958.
[22] Liu N, Luo T, Zhang J, et al. YF343, a novel histone deacetylase inhibitor, combined with CQ to inhibit- autophagy, contributes to increased apoptosis in triple-negative breast cancer[J]. Curr Med Chem, 2023,30:4605–4621.
[23] Guo J, Xu B, Han Q, et al. Ferroptosis: a novel anti-tumor action for cisplatin[J]. Cancer Res Treat, 2018,50:445–460.
[24] Zhou B, Liu J, KAang R, et al. Ferroptosis is a type of autophagy-dependent cell death[J]. Semin Cancer Biol, 2020,66:89–100.

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