Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

Liu, Peng; Wang, Wei; Zhou, Zhigang; Smith, Alan; Bowater, Richard P.; Wormstone, I. Michael; Chen, Yuqiong; Bao, Yongping

doi:10.3390/nu10050585

Cited by 20 publications

(10 citation statements)

References 51 publications

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“…Cells were then harvested and resuspended in PBS containing 10% DMSO. The alkaline Comet assay procedure was performed as previously described 38 . Levels of DNA strand breaks were expressed as tail intensity (% DNA in the Comet tail).…”

Section: Alkaline Comet Assaymentioning

confidence: 99%

Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes

Liu

Wang

Tang

et al. 2019

Food and Chemical Toxicology

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Sulforaphane (SFN) has shown anti-cancer effects in cellular and animal studies but its effectiveness has been limited in human studies. Here, the effects of SFN were measured in both human hepatocyte (HHL5) and hepatoma (HepG2) cells. Results showed that SFN inhibited cell viability and induced DNA strand breaks at high doses (≥ 20 µM). It also activated the nuclear factor (erythroidderived 2)-like 2 (Nrf2), and increased intracellular glutathione (GSH) levels at 24 hours. Pretreatment with a low dose SFN (≤5 µM) protected against hydrogen peroxide (H 2 O 2)-induced cell damage. High doses of SFN were more toxic towards HHL5 compared to HepG2 cells; the difference is likely due to the disparity in the responses of Nrf2-driven enzymes and-GSH levels between the two cell lines. In addition, HepG2 cells hijacked the cytoprotective effect of SFN over a wider dose range (1.25-20 µM) compared to HHL5. Manipulation of levels of GSH and Nrf2 in HepG2 cells confirmed that both molecules mediate the protective effects of SFN against H 2 O 2. The non-specific nature of SFN in the regulation of cell death and survival could present undesirable risks, i.e. be more toxic to normal cells, and cause chemo-resistance in tumor cells. These issues should be addressed in the context for cancer prevention and treatment before large scale clinical trials are undertaken.

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Section: Alkaline Comet Assaymentioning

confidence: 99%

Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes

Liu

Wang

Tang

et al. 2019

Food and Chemical Toxicology

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“…The antiproliferative effect of the BITC metabolites agrees with previous reports on the function of the ITC metabolites. [33][34][35] The BITC-GSH conjugate showed higher cytotoxicity than BITC-NAC (Figure 2B), possibly due to the different dissociation rate of BITC; the former was more rapid than the latter (Figure 4B). The tendency of the BITC dissociation from its metabolites was quite similar to the previously reported data.…”

Section: Discussionmentioning

confidence: 99%

Benzyl isothiocyanate and its metabolites inhibit cell proliferation through protein modification in mouse preosteoclast RAW264.7 cells

Nakamura

Tsutsui

Okuda

et al. 2022

J Biochem & Molecular Tox

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Benzyl isothiocyanate (BITC), derived from cruciferous vegetables, is an organosulfur compound exerting antiproliferative effects in several human cancer cells. In this study, we assessed BITC as a potential osteoclastogenesis inhibitor and investigated its underlying mechanism. BITC at 5 μM significantly decreased the viability of the osteoclast‐like differentiating RAW264.7 cells, coinciding with the downregulation of the primary biomarkers for osteoclast differentiation, such as the tartrate‐resistant acid phosphatase activity and nuclear factor of activated T‐cells gene expression. Not only BITC but also its metabolites, inhibited cell proliferation in the normal RAW264.7 cells, suggesting that BITC shows an anti‐osteoclastogenesis effect in vivo after its ingestion and metabolism, possibly through an antiproliferative action. Both BITC and its metabolites also enhanced the DNA fragmentation and the caspase‐3 activity, whereas their higher concentrations tended to suppress these effects. BITC was intracellularly accumulated when the cells were treated with its metabolites via their degradation into the free form. A quantitative experiment using the proteolysis/high performance liquid chromatography technique showed that the amount of BITC‐lysine thiourea in the cells was also increased in a time‐dependent manner, suggesting that lysine modification of the cellular proteins actually took place in the cells treated by BITC. Among the cellular proteins, the cleaved caspase‐3 was identified as a potential target for lysine modification by BITC. Taken together, BITC dissociated from its metabolites as well as its free form might modulate osteoclastogenesis, possibly through inhibition of cell proliferation by protein modification.

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“…It has an inhibitory effect on cellular escalation by induction of apoptosis (Jang et al., 2015). Previous studies have also highlighted the efficacy of SFN against HepG2 cell line for in vivo studies with xenograft models (Liu, Atkinson, et al., 2017; Liu, Wang, Zhou, et al., 2018; Zou et al., 2017). Another research study concluded that SFN inhibited the proliferation, migration, and invasion of hepatocellular carcinoma cells.…”

Section: Potential Effects Of Sulforaphane Against Different Cancersmentioning

confidence: 99%

Sulforaphane as a potential remedy against cancer: Comprehensive mechanistic review

Haq

Khan

Awan

et al. 2021

Journal of Food Biochemistry

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Sulforaphane belongs to the active class of isothiocyanates capable of delivering various biological benefits for health promotion and disease prevention. This compound is considered vital to curtail numerous metabolic disorders. Various studies have proven its beneficial effects against cancer prevention and its possible utilization as a therapeutic agent in cancer treatment. Understanding the mechanistic pathways and possible interactions at cellular and subcellular levels is key to design and develop cancer therapeutics for humans. In this respect, a number of mechanisms such as modulation of carcinogen metabolism & phase II enzymatic activities, cell cycle arrest, activation of Nrf2, cytotoxic, proapoptotic and apoptotic pathways have been reported to be involved in cancer prevention. This article provides sufficient information by critical analysis to understand the mechanisms involved in cancer prevention attributed to sulforaphane. Furthermore, various clinical studies have also been included for design and development of novel therapies for cancer prevention and cure. Practical applications Diet and dietary components are potential tools to address various lifestyle‐related disorders. Due to plenty of environmental and cellular toxicants, the chances of cancer prevalence are quite large which are worsen by adopting unhealthy lifestyles. Cancer can be treated with various therapies but those are acquiring side effects causing the patients to suffer the treatment regime. Nutraceuticals and functional foods provide safer options to prevent or delay the onset of cancer. In this regard, sulforaphane is a pivotal compound to be targeted as a potential agent for cancer treatment both in preventive and therapeutic regimes. This article provides sufficient evidence via discussing the underlying mechanisms of positive effects of sulforaphane to further the research for developing anticancer drugs that will help assuage this lethal morbidity.

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Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

Cited by 20 publications

References 51 publications

Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes

Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes

Benzyl isothiocyanate and its metabolites inhibit cell proliferation through protein modification in mouse preosteoclast RAW264.7 cells

Sulforaphane as a potential remedy against cancer: Comprehensive mechanistic review

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