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Review
. 2024 May 19;13(5):617.
doi: 10.3390/antiox13050617.

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers

Xiaochang Shen  1   2 , Jiandong Wang  1 , Boer Deng  1   2 , Ziyi Zhao  1   2 , Shuning Chen  1   2 , Weimin Kong  1 , Chunxiao Zhou  2   3 , Victoria Bae-Jump  2   3
Affiliations
Review

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers

Xiaochang Shen et al. Antioxidants (Basel). .

Abstract

Ascorbate (vitamin C) is an essential vitamin for the human body and participates in various physiological processes as an important coenzyme and antioxidant. Furthermore, the role of ascorbate in the prevention and treatment of cancer including gynecological cancer has gained much more interest recently. The bioavailability and certain biological functions of ascorbate are distinct in males versus females due to differences in lean body mass, sex hormones, and lifestyle factors. Despite epidemiological evidence that ascorbate-rich foods and ascorbate plasma concentrations are inversely related to cancer risk, ascorbate has not demonstrated a significant protective effect in patients with gynecological cancers. Adequate ascorbate intake may have the potential to reduce the risk of human papillomavirus (HPV) infection and high-risk HPV persistence status. High-dose ascorbate exerts antitumor activity and synergizes with chemotherapeutic agents in preclinical cancer models of gynecological cancer. In this review, we provide evidence for the biological activity of ascorbate in females and discuss the potential role of ascorbate in the prevention and treatment of ovarian, endometrial, and cervical cancers.

Keywords: ascorbate; gynecological cancer; prevention; treatment.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Fluctuations in plasma ascorbate concentration over the lifespans in males versus females. Females (Green) showed varying levels of plasma ascorbate concentration throughout their lifespan, reaching peak levels between the ages of 6 and 11, decreasing as they aged, and then rising slowly after reaching 40. Males (Yellow) displayed a comparable tendency to females, with lower plasma ascorbate concentrations than females at equivalent ages [29].
Figure 2
Figure 2
Physiological functions of ascorbate (Asc). Ascorbate plays distinct physiological functions in the body. Its primary function is to serve as a cofactor for over 20 types of oxygenase and to participate in various fundamental physiological processes, including collagen synthesis, carnitine production, hormone synthesis, amino acid metabolism, gene regulation, and epigenetic modification. Ascorbate acts as a scavenger to neutralize various harmful reactive oxygen species, thereby protecting nucleic acids, proteins, and lipids from oxidative damage. Furthermore, ascorbate increases the absorption of iron in the intestines by reducing ferric iron (Fe3+) to ferrous iron (Fe2+), marking it an effective iron absorption enhancer. Ascorbate also acts as an antioxidant and cofactor to protect immune cells and enhance innate and adaptive immune functions.
Figure 3
Figure 3
The antitumor activity of high-dose ascorbate (Asc) in gynecological cancers. With the catalysis of Fe3+, high-dose extracellular ascorbate generates substantial H2O2 and enhances Fe2+ uptake, initiating the Fenton reaction and continuously generating ROS, which eventually leads to cell death. Extracellular Asc can be transported into the cell through SVCT2 or converted to DHA and enter cells via GLUT1. Within cells, DHA can rapidly be reduced back to Asc by reduced glutathione (GSH), depleting GSH, and increasing ROS. In the cytoplasm, high-level Asc serves as a cofactor of enzymes to affect key molecular regulators such as HIF-1α, TET, and JHDM. Hence, high-dose ascorbate demonstrated potent antitumor activities in ovarian cancer, endometrial cancer, and cervical cancer. (↑: increase, ↓: decrease, -: no significant change, EC: endometrial cancer).
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