Vitamin C enhances anticancer activity in methotrexate-treated Hep3B hepatocellular carcinoma cells

Abstract

Methotrexate (MTX) has been widely used for rheumatoid arthritis therapy for a long time. MTX is also used as an anticancer drug for various tumors. However, many studies have shown that high-dose MTX treatment for cancer therapy may cause liver and renal damage. Alhough the mechanisms involved in MTX-induced liver and renal damage require further research, many studies have indicated that MTX-induced cytotoxicity is associated with increases in oxidative stress and caspase activation. In order to reduce MTX-induced side-effects and increase anticancer efficiency, currently, combination treatments of low-dose MTX and other anticancer drugs are considered and applied for various tumor treatments. The present study showed that MTX induces increases in H2O2 levels and caspase-9/-3 activation leading to cell death in hepatocellular carcinoma Hep3B cells. Importantly, this study is the first to demonstrate that vitamin C can efficiently aid low-dose MTX in inducing cell death in Hep3B cells. Therefore, the present study provides a possible powerful therapeutic method for tumors using a combined treatment of vitamin C and low-dose MTX.

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways

“…In addition, MTX has been applied for clinical cancer treatment (13,14). Previous studies demonstrated that MTX can inhibit the growth of various cancer cells, including hepatoma, leukemia, lymphoma and gastric cancer cells (15)(16)(17). Nevertheless, MTX alone is not effective for breast cancer treatment.…”

“…Vitamin C, a common nutrient, has anti-oxidative (26,27) and anticancer activities (28,29). Previous studies have also demonstrated that combined treatment with vitamin C and conventional anticancer agents can enhance anticancer activities (15,30,31). Currently, vitamin C supplements are being applied for clinical cancer therapy (32)(33)(34).…”

Ascorbic Acid in Cancer: A Renewed Hope?

“…When AA is combined with a glycolysis inhibitor, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen -1-one (3-PO), a synergistic induction of apoptosis via a ROSdependent pathway in non-small cell carcinoma cell lines (H1299, H661 and A549) was observed [13]. In addition, AA was shown to potentiate low dose methotrexate in inducing cancer cell death by caspase 3 and caspase 9 activation in hepatocellular carcinoma cells (Hep3B) [14].…”

Ascorbic acid modulates doxorubicin and cyclophosphamide-induced cytogenetic damages in Sarcoma 180 cells

“…There are also reports indicating that AA can enhance the effectiveness of chemotherapeutic agents that can reduce the cytotoxicity of anticancer drugs, and also may prevent free radicals and neutralize some carcinogens [14,46,47]. The identification of the variety of responses to cancer therapy requires knowledge of variables, including concomitant medications, which may alter the metabolism and pharmacokinetics of chemotherapy.…”