Vitamin C: attenuating effect on growth and proliferation in systemic malignancies

The recent article by J. Cha et al. provided for highly interesting reading [1].Vitamin C may attenuate tumor growth in a number of other systemic malignancies.

Vitamin C has a negative impact on tumor growth in breast cancers. Similarly it mitigates tumor metastasis. It mediates this effect in part by attenuating IL-6 levels [2]. Similar effect is seen on VEGF levels. Interestingly, intravenous ascorbic acid has been shown to significantly improve the quality of life in breast cancer survivors during chemotherapy [3]. For instance, symptoms such as depression and nausea are markedly decreased. Enhanced anti-proliferative effects are seen when vitamin C is administered in conjunction with agents such as retinoic acid [4]. In one recent study, the reported synergistic ratio of retinoic acid and vitamin C was 1.72. Vitamin C also augments the anti-neoplastic activity of chemotherapeutic agents such as cisplatin [5]. Similarly it increases the sentivity of breast cancer cells to agents such as doxorubicin.

Similar effects are seen in gastric malignancies. Vitamin C tends to augment intra-tumoral apoptosis. It mediates this effect by down-regulating 14–3–3σ via a mitochondrial dependent pathway [6]. Part of these pro-apoptotic effects are also mediated via p38-MAP kinase-dependent up-regulation of transferrin receptor [7]. It also increases the Bax/ Bcl-xL ratio. These effects are dose dependent. Administration of vitamin C also augments superoxide dismutase activity. Vitamin C also enhances MHC class I expression by the cancerous cells [8]. At the same time Fas (CD95) expression is markedly augmented. As a result the sensitivity of cancer cells to anti-Fas antibodies is significantly accentuated.

Similarly, decreased RBC vitamin C levels have been noted in patients with prostate carcinomas. In fact, recent studies indicate that vitamin C markedly attenuates tumor growth in hormone refractory prostatic malignancies [9]. It also has a negative impact on tumor metastasis. Part of these effects are mediated via VEGF inhibition. At the same time vitamin C has an inhibitory effect on MMP-9 [10].

The above examples clearly highlight the significant anti-neoplastic effects of vitamin C.

REFERENCES

1. Cha J, Roomi MW, Ivanov V, et al. Ascorbate depletion increases growth and metastasis of melanoma cells in vitamin C deficient mice. Exp Oncol 2011; 33: 226–230.
2. Cha J, Roomi MW, Ivanov V, et al. Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C-deficient mice. Int J Oncol 2013; 42: 55–64.
3. Vollbracht C, Schneider B, Leendert V, et al. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo 2011; 25: 983–90.
4. Kim KN, Pie JE, Park JH, et al. Retinoic acid and ascorbic acid act synergistically in inhibiting human breast cancer cell proliferation. J Nutr Biochem 2006; 17: 454–62.
5. Kurbacher CM, Wagner U, Kolster B, et al. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett 1996; 103: 183–9.
6. Ha YM, Park MK, Kim HJ, et al. High concentrations of ascorbic acid induces apoptosis of human gastric cancer cell by p38-MAP kinase-dependent up-regulation of transferrin receptor. Cancer Lett 2009; 277: 48–54.
7. Nagappan A, Park KI, Park HS, et al. Vitamin C induces apoptosis in AGS cells by down-regulation of 14–3-3sigma via a mitochondrial dependent pathway. Food Chem 2012; 135: 1920–8.
8. Yu Y, Bae S, Kim H, et al. The anti-tumor activity of vitamin C via the increase of Fas (CD95) and MHC I expression on human stomach cancer cell line, SNU1. Immune Netw 2011; 11: 210–5.
9. Surapaneni KM, Ramana V. Erythrocyte ascorbic acid and plasma vitamin E status in patients with carcinoma of prostate. Ind J Physiol Pharmacol 2007; 51: 199–202.
10. Pollard HB, Levine MA, Eidelman O, Pollard M. Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone-refractory prostate cancer. In Vivo 2010; 24: 249–55.

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