Water extract of Hedyotis Diffusa Willd suppresses proliferation of human HepG2 cells and potentiates the anticancer efficacy of low-dose 5-fluorouracil by inhibiting the CDK2-E2F1 pathway

3-Iodothyronamine (T1AM) and its synthetic analog SG-2 are rapidly emerging as promising drivers of cellular metabolic reprogramming. Our recent research indicates that in obese mice a sub-chronic low dose T1AM treatment increased lipolysis, associated with significant weight loss independent of food consumption. The specific cellular mechanism of T1AM’s lipolytic effect and its site of action remains unknown. First, to study the mechanism used by T1AM to gain entry into cells, we synthesized a fluoro-labeled version of T1AM (FL-T1AM) by conjugating it to rhodamine (TRITC) and analyzed its cellular uptake and localization in 3T3-L1 mouse adipocytes. Cell imaging using confocal microscopy revealed a rapid intercellular uptake of FL-T1AM into mitochondria without localization to the lipid droplet or nucleus of mature adipocytes. Treatment of 3T3-L1 adipocytes with T1AM and SG-2 resulted in decreased lipid accumulation, the latter showing a significantly higher potency than T1AM (10 µM vs. 20 µM, respectively). We further examined the effects of T1AM and SG-2 on liver HepG2 cells. A significant decrease in lipid accumulation was observed in HepG2 cells treated with T1AM or SG-2, due to increased lipolytic activity. This was confirmed by accumulation of glycerol in the culture media and through activation of the AMPK/ACC signaling pathways.

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The effect of pre-low-dose X-ray radiation on tumor inhibition of HepG2 cells in tumor-bearing nude mice

The Chinese-German Journal of Clinical Oncology ◽

10.1007/s10330-012-0976-y ◽

2012 ◽

Vol 11 (6) ◽

pp. 340-343 ◽

Cited By ~ 2

Author(s):

Weihua Sun ◽

Hongsheng Yu ◽

Qingjun Shang

Keyword(s):

Nude Mice ◽

Hepg2 Cells ◽

Low Dose ◽

Tumor Inhibition ◽

X Ray ◽

Tumor Bearing

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Artemisia iwayomogiplusCurcuma longaSynergistically Ameliorates Nonalcoholic Steatohepatitis in HepG2 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/4390636 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Hyeong-Geug Kim ◽

Sung-Bae Lee ◽

Jin-Seok Lee ◽

Won-Young Kim ◽

Seung-Hoon Choi ◽

...

Keyword(s):

Er Stress ◽

Nonalcoholic Steatohepatitis ◽

Hepg2 Cells ◽

Curcuma Longa ◽

Water Extract ◽

Underlying Mechanism ◽

Liver Disorders ◽

Artemisia Iwayomogi ◽

Clinical Potential ◽

Intracellular Triglyceride

The combination ofArtemisia iwayomogiandCurcuma longaradix is frequently prescribed for liver diseases in TKM. However, the synergic effects of the two herbs on nonalcoholic steatohepatitis (NASH) have not yet been studied. Therefore, we investigated the anti-NASH effects of the water extract ofA. iwayomogi(AI),C. longaradix (CL), and combination of the two herbs (ACE). Hepatic steatosis and NASH were induced in HepG2 cells by treatment with palmitic acid (PA, for 6 h) with/without pretreatment of ACE (25 or 50 μg/mL), AI (50 or 100 μg/mL), CL (50 or 100 μg/mL), curcumin (5 μg/mL), or scopoletin (5 μg/mL). The PA treatment (200 μM) drastically altered intracellular triglyceride levels, total cholesterol, and expression levels of genes related to lipid metabolism (CD36, SREBP1c, PPAR-γ, and PPAR-α), whereas pretreatment with ACE significantly attenuated these alterations. ACE also protected HepG2 cells from PA- (300 μM-) induced endoplasmic reticulum (ER) stress and apoptosis and attenuated the related key molecules including GRP78, eIF2, and CHOP, respectively. In conclusion, we found synergic effects ofA. iwayomogiandC. longaon NASH, supporting the clinical potential for fatty liver disorders. In addition, modulation of ER stress-relative molecules would be involved in its underlying mechanism.

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LINE-1 gene hypomethylation and p16 gene hypermethylation in HepG2 cells induced by low-dose and long-term triclosan exposure: The role of hydroxyl group

Toxicology in Vitro ◽

10.1016/j.tiv.2016.03.002 ◽

2016 ◽

Vol 34 ◽

pp. 35-44 ◽

Cited By ~ 14

Author(s):

Liudan Zeng ◽

Huimin Ma ◽

Shangxia Pan ◽

Jing You ◽

Gan Zhang ◽

...

Keyword(s):

Hepg2 Cells ◽

Low Dose ◽

Hydroxyl Group ◽

P16 Gene

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Gene expression analysis in the high and low-dose epigallocatechin-3-gallate and propyl gallate-treated HepG2 cells

Toxicology Letters ◽

10.1016/j.toxlet.2008.06.374 ◽

2008 ◽

Vol 180 ◽

pp. S120

Author(s):

Joon-Ik Ahn ◽

Moon-Jeong Ko ◽

Ho-Sang Jeong ◽

Hye Joo Chung

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Propyl Gallate ◽

Hepg2 Cells ◽

Gene Expression Analysis ◽

Low Dose

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Metals and low dose IR: Molecular effects of combined exposures using HepG2 cells as a biological model

Journal of Hazardous Materials ◽

10.1016/j.jhazmat.2020.122634 ◽

2020 ◽

Vol 396 ◽

pp. 122634 ◽

Cited By ~ 1

Author(s):

A. Campos ◽

R. Pereira ◽

A. Vaz ◽

T. Caetano ◽

M. Malta ◽

...

Keyword(s):

Hepg2 Cells ◽

Low Dose ◽

Biological Model ◽

Combined Exposures ◽

Molecular Effects

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Low-Dose Berberine Attenuates the Anti-Breast Cancer Activity of Chemotherapeutic Agents via Induction of Autophagy and Antioxidation

Dose-Response ◽

10.1177/1559325820939751 ◽

2020 ◽

Vol 18 (4) ◽

pp. 155932582093975

Author(s):

Bing Han ◽

Kai Wang ◽

Yanbei Tu ◽

Lihua Tan ◽

Chengwei He

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Low Dose ◽

Negative Impact ◽

Adenosine Monophosphate ◽

Chemotherapeutic Agents ◽

Related Factor ◽

Anticancer Efficacy ◽

Hormetic Effect ◽

Underlying Mechanisms

Berberine (BBR), a major active component of Rhizoma coptidis, is one of the most promising agents for breast cancer adjuvant therapy. It is well accepted that BBR could exhibit remarkable anticancer efficacy with few side effects, and when treated with chemotherapeutic agents in combination, BBR could enhance the chemosensitivity of cancer cells. Our previous study reported that low-dose BBR (LDB) induced hormetic effect and attenuated the anticancer activity of chemotherapeutic agents. However, the underlying mechanisms are still unclear. In this study, we confirmed that LDB could promote cancer cell proliferation and antagonize the anti-breast cancer activities of chemotherapeutic agents. And the mechanisms were proved to be induction of autophagy and antioxidation by LDB. Our results showed that LDB could mildly induce reactive oxygen species, raise the level of autophagy by promoting the phosphorylation of adenosine monophosphate-activated protein kinase, and promote antioxidant enzymes expression through activating nuclear factor erythroid 2-related factor 2 in breast cancer cells. These findings revealed a potential negative impact of BBR on its adjuvant anti-breast cancer therapy, providing guidance for a safe and effective use of naturally originated medicines in the clinic.

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