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. 2016 Nov;12(5):3058-3062.
doi: 10.3892/etm.2016.3707. Epub 2016 Sep 16.

In vitro and in vivo Assessment of High-Dose Vitamin C Against Murine Tumors

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Free PMC article

In vitro and in vivo Assessment of High-Dose Vitamin C Against Murine Tumors

Guoping Wang et al. Exp Ther Med. .
Free PMC article

Abstract

Vitamin C is widely used in clinical settings and is well known for its safety. Previous studies have shown the efficacy of intravenous vitamin C; however, intratumoral delivery of vitamin C has yet to be attempted. In the present study, the biological effects of high-dose vitamin C on tumor cells were investigated in vitro by using the MTT assay and flow cytometry. When administered in vitro, high-dose vitamin C inhibited the proliferation of murine colon and breast cancer cells, and induced tumor cell apoptosis. Cytotoxicity of vitamin C was partially reversed by N-acetyl-cysteine at a relatively low dosage. In addition, synergistic anti-tumor effects of vitamin C and cisplatin were observed. In vivo, intratumoral delivery of vitamin C delayed tumor growth in murine solid tumor models. Considering its low toxicity and availability, the present study indicates that vitamin C may be a novel therapeutic method for patients with advanced tumors.

Keywords: N-acetyl-cysteine; apoptosis; chemotherapy; proliferation; tumor; vitamin C.

Figures

Figure 1.
Figure 1.
Vitamin C inhibits tumor cell proliferation. (A) Murine 4T1 breast cancer cells and (B) CT26 colon cancer cells were treated with 100 and 200 µg/ml vitamin C for 72 h. MTT assays were performed at 0, 24, 48 and 72 h. Vitamin C significantly inhibited tumor cells proliferation in vitro. *P<0.01 vs. the control group. OD, optical density; ctrl, control.
Figure 2.
Figure 2.
Vit C induces tumor cells apoptosis. CT26 tumor cells were exposed to various doses of vitamin C for 24 h. Flow cytometry was performed. (A) Representative flow cytometry of CT26 cells treated with 200 µg/ml vit C; (B) quantification of apoptotic cells following exposure to various doses of vit C. High doses of vit C induced the apoptosis of tumor cells. *P<0.05 vs. the control group. Ctrl, control; vit, vitamin.
Figure 3.
Figure 3.
NAC partially antagonizes the tumoricidal effect of vit C. CT26 tumor cells were treated with 200, 500 and 1,000 µg/ml vit C for 24 h, and 2 mM NAC was used to block the effect of vit C. Annexin-V-positive apoptotic cells were assessed by flow cytometry. NAC antagonized the cytotoxicity of vitamin C. *P<0.05 vs. (−) NAC group in the presence of 200 µg/ml vit C; **P<0.01 vs. (−) NAC group in the presence of 500 µg/ml vit C. NAC, N-acetyl-cysteine; Vit, vitamin; MFI, mean fluorescence intensity.
Figure 4.
Figure 4.
Vit C enhances the anti-tumor effect of cisplatin. CT26 tumor cells were treated with 1 mg/ml cisplatin and/or 200 µg/ml vit C for 48 h. Flow cytometry was performed to assess the synergistic anti-tumor effect. The addition of vit C enhanced the anti-tumor effect of chemotherapy. *P<0.05 vs. control; #P<0.05 vs. cisplatin or vitamin C single drug. Vit, vitamin; ctrl, control.
Figure 5.
Figure 5.
Intratumoral delivery of escalating doses of vitamin C retards tumor growth. Scheme of drug administration in (A) CT26 and (B) 4T1 tumor-bearing mice. (C) Mice bearing CT26 cancer cells were treated with vitamin C. Tumor volume was tracked and calculated at the 26th day (n=6). (D) 4T1 tumor-bearing mice were treated with vitamin C. Tumor volume was tracked and calculated at 32nd day (n=5). *P<0.05 vs. control; ctrl, control.

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