Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2

Lv, Hongwei; Wang, Changzheng; Fang, Tian; T, Li; Lv, Guishuai; Han, Qin; Yang, Wen; Wang, Hongyang

doi:10.1038/s41698-017-0044-8

Cited by 156 publications

(154 citation statements)

References 44 publications

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“…Therefore, SVCT2 might be implicated in the ascorbate induced cancer cell death phenomena. Similar results were observed by two groups in cholangiocarcinoma cells (Wang et al, 2017), hepatocellular carcinoma (Lv et al, 2018) and colon cancer cells (Cho et al, 2018), where SVCT2 expression determines the susceptibility to pharmacological ascorbate-induced cell death.…”

Section: Vitamin C Transport and Compartmentalization In Cancer Cellssupporting

confidence: 86%

“…Another report performed in 73 patients with acute myeloid leukemia showed that IV ascorbate treatment combined with chemotherapy produced a higher complete remission and prolonged survival compared to patients who received only chemotherapy (Zhao et al, 2018). In a retrospective study in 613 hepatocellular carcinoma patients, it was shown that IV ascorbate administration improved disease-free survival of patients after surgery (Lv et al, 2018). Finally, a phase I metastatic colorectal and gastric cancer study in 36 patients applying high-dose AA in combination with mFOLFOX6 or FOLFIRI, showed potential clinical efficacy in these patients (Wang et al, 2019).…”

Section: Vitamin C Administration In Clinical Studiesmentioning

confidence: 99%

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Therapeutic Use of Vitamin C in Cancer: Physiological Considerations

et al. 2020

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Since the early studies of William J. McCormick in the 1950s, vitamin C has been proposed as a candidate for the treatment of cancer. A number of reports have shown that pharmacological concentrations of vitamin C selectively kill cancer cells in vitro and decrease the growth rates of a number of human tumor xenografts in immunodeficient mice. However, up to the date there is still doubt regarding this possible therapeutic role of vitamin C in cancer, mainly because high dose administration in cancer patients has not showed a clear antitumor activity. These apparent controversial findings highlight the fact that we lack information on the interactions that occurs between cancer cells and vitamin C, and if these transformed cells can uptake, metabolize and compartmentalize vitamin C like normal human cells do. The role of SVCTs and GLUTs transporters, which uptake the reduced form and the oxidized form of vitamin C, respectively, has been recently highlighted in the context of cancer showing that the relationship between vitamin C and cancer might be more complex than previously thought. In this review, we analyze the state of art of the effect of vitamin C on cancer cells in vitro and in vivo, and relate it to the capacity of cancer cells in acquiring, metabolize and compartmentalize this nutrient, with its implications on the potential therapeutic role of vitamin C in cancer.

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Section: Vitamin C Transport and Compartmentalization In Cancer Cellssupporting

confidence: 86%

Section: Vitamin C Administration In Clinical Studiesmentioning

confidence: 99%

Therapeutic Use of Vitamin C in Cancer: Physiological Considerations

et al. 2020

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“…Several studies have demonstrated that L-ascorbic acid/VC, in addition to its role in cancer treatment, [35][36][37][38] promotes mammalian cell differentiation and DNA synthesis. 6,27,30,32 However, the impact of VC on the differentiation and effector function of human γδ T cells has not been addressed to date.…”

Section: Discussionmentioning

confidence: 99%

Vitamin C promotes the proliferation and effector functions of human γδ T cells

Kouakanou

Peters

et al. 2019

Cell Mol Immunol

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γδ T cells are of interest as effector cells for cellular immunotherapy due to their HLA-non-restricted lysis of many different tumor cell types. Potential applications include the adoptive transfer of in vitro-expanded γδ T cells. Therefore, it is important to optimize the culture conditions to enable maximal proliferative and functional activity. Vitamin C (L-ascorbic acid) is an essential vitamin with multiple effects on immune cells. It is a cofactor for several enzymes, has antioxidant activity, and is an epigenetic modifier. Here, we investigated the effects of vitamin C (VC) and its more stable derivative, L-ascorbic acid 2-phosphate (pVC), on the proliferation and effector function of human γδ T cells stimulated with zoledronate (ZOL) or synthetic phosphoantigens (pAgs). VC and pVC did not increase γδ T-cell expansion within ZOL-or pAg-stimulated PBMCs, but increased the proliferation of purified γδ T cells and 14-day-expanded γδ T-cell lines in response to γδ T-cell-specific pAgs. VC reduced the apoptosis of γδ T cells during primary stimulation. While pVC did not prevent activation-induced death of pAg-restimulated γδ T cells, it enhanced the cell cycle progression and cellular expansion. Furthermore, VC and pVC enhanced cytokine production during primary activation, as well as upon pAg restimulation of 14-day-expanded γδ T cells. VC and pVC also increased the oxidative respiration and glycolysis of γδ T cells, but stimulus-dependent differences were observed. The modulatory activity of VC and pVC might help to increase the efficacy of γδ T-cell expansion for adoptive immunotherapy.

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“…Several studies during the past decade confirmed that pharmacological concentrations of Vit.C in the millimolar range are effective in in vitro studies as they kill cancer cells, and in vivo by slowing down the tumor growth [9,98]. However, the mechanism behind the sensitivity of cancer cells to Vit.C and resistance of normal cells to Vit.C is still not clearly understood and needs further investigation.…”

Section: Vitc and Its Anticancer Mechanismmentioning

confidence: 99%

Combination Therapy with Vitamin C Could Eradicate Cancer Stem Cells

2020

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Cancer remains one of the most feared and dreaded diseases in this era of modern medicine, claiming the lives of many, and affecting the quality of life of several others around the globe despite major advances in the diagnosis, treatment, palliative care and the immense resources invested into cancer research. While research in cancer has largely focused on the neoplasm/tumor and the cancerous cells that make up the tumor, more recently, the existence, proliferation, differentiation, migration and invasion of cancer stem cells (CSCs) and the role that CSCs play in tumor initiation, progression, metastasis, drug resistance and relapse/recurrence of the disease has gained widespread interest in cancer research. Although the conventional therapeutic approaches such as surgery, chemotherapy and radiation therapy are effective cancer treatments, very often these treatment modalities fail to target the CSCs, which then later become the source of disease recurrence. A majority of the anti-cancer agents target rapidly dividing cancer cells and normal cells and hence, have side effects that are not expected. Targeting CSCs remains a challenge due to their deviant nature with a low proliferation rate and increased drug resistance mechanism. Ascorbic acid/Vitamin C (Vit.C), a potent antioxidant, is a cofactor for several biosynthetic and gene regulatory enzymes and a vital contributor to immune defense of the body, and was found to be deficient in patients with advanced stages of cancer. Vit.C has gained importance in the treatment of cancer due to its ability to modulate the redox status of the cell and influence epigenetic modifications and significant roles in HIF1α signaling. Studies have reported that intravenous administration of Vit.C at pharmacological doses selectively kills tumor cells and targets CSCs when administered along with chemotherapeutic drugs. In the current article, we provide an in-depth review of how Vit.C plays an important role in targeting CSCs and its possible use as an adjuvant, neoadjuvant or co-treatment in the treatment of cancers.

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Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2

Cited by 156 publications

References 44 publications

Therapeutic Use of Vitamin C in Cancer: Physiological Considerations

Therapeutic Use of Vitamin C in Cancer: Physiological Considerations

Vitamin C promotes the proliferation and effector functions of human γδ T cells

Combination Therapy with Vitamin C Could Eradicate Cancer Stem Cells

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