A secretome profile indicative of oleate-induced proliferation of HepG2 hepatocellular carcinoma cells

Park, Soyeon; Park, Ji-Hwan; Jung, Heejung; Jang, Jin-Wook; Ahn, Sanghyun; Kim, Younah; Suh, Pann‐Ghill; Chae, Sehyun; Yoon, Jong Hyuk; Ryu, Sung Ho; Hwang, Daehee

doi:10.1038/s12276-018-0120-3

Cited by 14 publications

(12 citation statements)

References 85 publications

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“…Previous studies reported cell proliferation inhibition and apoptosis induction after OA administration in carcinoma cells (Carrillo et al, 2012). In previous works unsaturated fatty acid oleate (an oleic acid-derived salt) induces (Vinciguerra et al, 2009;Park et al, 2018) or inhibits (Arous et al, 2011;Li et al, 2013) HepG2 cell proliferation in a concentration-dependent manner, with a mechanism only partially elucidated. We report here that increasing doses of OA reduce viability and increase cell death (Figure 4) in both HCC cell lines.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction

Giulitti

Petrungaro

Mandatori

et al. 2021

Front. Cell Dev. Biol.

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Oleic acid (OA) is a component of the olive oil. Beneficial health effects of olive oil are well-known, such as protection against liver steatosis and against some cancer types. In the present study, we focused on OA effects in hepatocellular carcinoma (HCC), investigating responses to OA treatment (50–300 μM) in HCC cell lines (Hep3B and Huh7.5) and in a healthy liver-derived human cell line (THLE-2). Upon OA administration higher lipid accumulation, perilipin-2 increase, and autophagy reduction were observed in HCC cells as compared to healthy cells. OA in the presence of 10% FBS significantly reduced viability of HCC cell lines at 300 μM through Alamar Blue staining evaluation, and reduced cyclin D1 expression in a dose-dependent manner while it was ineffective on healthy hepatocytes. Furthermore, OA increased cell death by about 30%, inducing apoptosis and necrosis in HCC cells but not in healthy hepatocytes at 300 μM dosage. Moreover, OA induced senescence in Hep3B, reduced P-ERK in both HCC cell lines and significantly inhibited the antiapoptotic proteins c-Flip and Bcl-2 in HCC cells but not in healthy hepatocytes. All these results led us to conclude that different cell death processes occur in these two HCC cell lines upon OA treatment. Furthermore, 300 μM OA significantly reduced the migration and invasion of both HCC cell lines, while it has no effects on healthy cells. Finally, we investigated autophagy role in OA-dependent effects by using the autophagy inducer torin-1. Combined OA/torin-1 treatment reduced lipid accumulation and cell death as compared to single OA treatment. We therefore concluded that OA effects in HCC cells lines are, at least, in part dependent on OA-induced autophagy reduction. In conclusion, we report for the first time an autophagy dependent relevant anti-cancer effect of OA in human hepatocellular carcinoma cell lines.

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Section: Discussionmentioning

confidence: 99%

Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction

Giulitti

Petrungaro

Mandatori

et al. 2021

Front. Cell Dev. Biol.

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“…ERp57 expression significantly differs among HCC patients, at-risk patients and healthy individuals, thereby potentially serving as a biomarker for the early diagnosis of HCC 6 . Evidence suggests that ERp57 is overexpressed in HCC, colorectal cancer 30 and breast cancer 31 , 32 and participates in tumorigenesis and the progression of cancer 3 , 4 . ERp57 expression is associated with the metastatic capacity of cancer cells.…”

Section: Clinical Implications Of Erp57 In Cancermentioning

confidence: 99%

“…To ease the burden of cancer, current research is focusing largely on molecular preventive trials, which are regarded as the priority study type; biomarkers are key determinants of molecular prevention that allow us to evaluate the natural history of cancer as well as the efficacy and toxicity of an agent [2]. Recent research regarding the expression of endoplasmic reticulum resident protein 57 (ERp57) in tumors revealed that ERp57 expression is upregulated in various cancers and participates in cancer initiation, progression and chemosensitivity [3][4][5]. Some evidence suggests that ERp57 can serve as a potential molecular marker and therapeutic target of cancer [6].…”

Section: Introductionmentioning

confidence: 99%

Insights into the role of ERp57 in cancer

Song¹,

Líu²,

Wu³

et al. 2021

J. Cancer

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Endoplasmic reticulum resident protein 57 (ERp57) has a molecular weight of 57 kDa, belongs to the protein disulfide-isomerase (PDI) family, and is primarily located in the endoplasmic reticulum (ER). ERp57 functions in the quality control of nascent synthesized glycoproteins, participates in major histocompatibility complex (MHC) class I molecule assembly, regulates immune responses, maintains immunogenic cell death (ICD), regulates the unfolded protein response (UPR), functions as a 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) receptor, regulates the NF-κB and STAT3 pathways, and participates in DNA repair processes and cytoskeletal remodeling. Recent studies have reported ERp57 overexpression in various human cancers, and altered expression and aberrant functionality of ERp57 are associated with cancer growth and progression and changes in the chemosensitivity of cancers. ERp57 may become a potential biomarker and therapeutic target to combat cancer development and chemoresistance. Here, we summarize the available knowledge of the role of ERp57 in cancer and the underlying mechanisms.

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“…NASH is characterized by accumulation of fat in liver cells. Oleate acid (OA), one of fatty acids that induce cellular adipogenesis, can promote the proliferation of HCC cells [42,43]. OA-induced lipid accumulation in HepG2 liver cancer cells is a well-established model for the investigation of hepatic steatosis [20].…”

Section: Oleate Acid Elevates the Expression Of Hmmr Via Cebpαmentioning

confidence: 99%

Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma

Zhang¹,

Liu²,

Xie³

et al. 2020

Int. J. Biol. Sci.

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Non-alcoholic steatohepatitis (NASH) is a type of nonalcoholic fatty liver disease and has become a major risk factor for hepatocellular carcinoma (HCC). However, the underlying pathophysiological mechanisms are still elusive. Here, we identify hyaluronan-mediated motility receptor (HMMR) as a critical gene associated with NASH/HCC by combination of bioinformatic analysis and functional experiments. Analysis of differentially expressed genes (DEGs) between normal controls and NASH/HCC identified 5 hub genes (HMMR, UBE2T, TYMS, PTTG1 and GINS2). Based on the common DEGs, analyses of univariate and multivariate Cox regression and the area under the curve (AUC) value of the receiver operating characteristic (ROC) indicate that HMMR is the most significant gene associated with NASH/HCC among five hub genes. Oleate acid (OA), one of fatty acids that induce cellular adipogenesis, stimulates HMMR expression via CCAAT/enhancer-binding protein α (CEBPα). CEBPα increases the expression of HMMR through binding to its promoter. HMMR promotes HCC cell proliferation in vitro via activation of G1/S and G2/M checkpoint transitions, concomitant with a marked increase of the positive cell cycle regulators, including cyclin D1, cyclin E, and cyclin B1. Knockdown of HMMR suppresses HCC tumor growth in nude mice. Our study identifies an important role of HMMR in NASH/HCC, and suggests that HMMR may be a useful target for therapy and prognostic prediction of NASH/HCC patients.

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A secretome profile indicative of oleate-induced proliferation of HepG2 hepatocellular carcinoma cells

Cited by 14 publications

References 85 publications

Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction

Anti-tumor Effect of Oleic Acid in Hepatocellular Carcinoma Cell Lines via Autophagy Reduction

Insights into the role of ERp57 in cancer

Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma

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