A Closer Look at the Working of Antioxidants in Cancer Patients

A Closer Look at the Working of Antioxidants in Cancer Patients

Antioxidants are always debated as to their merits in the treatment of cancer patients. Especially when people are on chemotherapy this question is often asked, so let’s have a closer look at the working of antioxidants and also their merits and exceptions for use.

Antioxidants Anticancer Mechanisms:

  1. Antioxidants inhibit protein kinase c, restraining tumour cell division and proliferation
  2. Antioxidants inhibit oncogene expression, genes that give rise to tumours
  3. Antioxidants promote differentiation by altering growth factors. Undifferentiated cells depart (in appearance) from the highly recognizable (differentiated) cells of the tissue of origin
  4. Antioxidants block destruction imposed by free radicals, protecting vital tissue from damage

Exceptions & Contraindications for the use of Antioxidants

Three agents, classified as antioxidants, have been shown to decrease the effectiveness of radiation or chemotherapy in vivo (1) :

  1. N-acetyl cysteine (NAC) reduced the therapeutic effect of anthracycline –type chemotherapy agents (doxorubicin and bleomycin), which kill cells by generating oxygen radicals. Alkylating agents (such as cisplatin) and hormonal therapies were not affected
  2. Beta-carotene decreased the effectiveness of antimetabolites (5-fluoruracil and methotrexate). Conversely, beta carotene increased the efficacy of radiotherapy, as well as alkylating agents, anthracycline, and platinum chemotherapy agents
  3. Tangeretin (a flavanoid found in citrus fruit) reduced the chemotherapeutic effect of platinum compounds such as cisplatin and carboplatin. Tangeretin interfered with tamoxifen, a nonsteroidal antiestrogen used to treat estrogen-dependent cancers.

High Dose Antioxidants
During Chemotherapy
& Radiation

Studies have demonstrated that antioxidant vitamins can enhance the efficacy of certain chemotherapeutic agents on tumor cells in culture (2). Antioxidant vitamins could be an important adjuvant to standard treatment of human cancers (3)

An in vivo study : antioxidant vitamins could enhance the cytotoxic and apoptotic effects of paclitaxel and carboplatin on non-small cell lung cancer. (4)  The human non-small cell lung cancer cell line H-520 was treated with a mixture of the antioxidant vitamins c,e, and beta carotene and paclitaxel and carboplatin, both individually and in combination of various doses in different sequences.

The apoptosis achieved was as follows :

  • antioxidant vitamins : 15%
  • paclitaxel and carboplatin 40%
  • paclitaxel treatment 24 hours prior to carboplatin treatment caused 54% apoptosis
  • cells pretreated with an antioxidant vitamin mixture immediately before treatment with paclitaxel and carboplatin 70% apoptosis
  •  pretreated with the antioxidant mixture 24hrs prior to treatment with paclitaxel, then followed 24hrs later by treatment with carboplatin 89% apoptosis

Some leaders in the field endorse pulse therapy as the appropriate means of administering nutritional support concurrent with toxic treatments.    Re-entering the supplementation 2-3 days after the large chemotherapeutic bolus allows time for a massive cancer kill followed by a period of rebuilding (5).     If using conventional treatment, this dosing allows the body the full effects of conventional treatments, plus the benefit of an antioxidant program a few days later.

Another study on advanced colorectal cancer (6) using 12 patients using 750mg vit e 2 weeks prior to chemotherapy and radiation showed that short term supplementation increased cd4:cd8, enhanced T-cell to produce T helper 1 cytokines, interleukin 2 and interferon gamma.Dietary vit e may be used to improve the immune functions in patients with advanced cancer.

Another systematic review (7) evaluated the efficacy of CoQ10 for improved tolerability of cancer treatments. The results suggested that coq10 provides some protection against cardiotoxicity or liver toxicity during cancer treatement.

A landmark paper by block (8) on the use of antioxidants and cancer chemotherapy published in 2007 is summarized as follows :

  • 19 trials, randomized, concurrent with chemotherapy
  • survival or response was reported
  • glutathione, melatonin, vit A, Vit C, Vit e, NAC, egalilic, Mix were used
  • none reported decrease in efficacy of chemotherapy
  • many reported :
    • increased survival time
    • tumor response
    • fewer toxicities

The Chemotherapeutic
Effects of High Dose
Intravenous Vit C :

  1. Remember at high doses, iv vit c is a pro-oxidant not an antioxidant
  2. Immune system enhancement
  3. H2O2 (hydrogen peroxide) production, most tumor cells are catalase deficient and cannot metabolize this (9)
  4. Apoptosis (increase in p53, p21, cellular Ca, and a decrease in mitochondrial membrane potential and activation of caspase 3. (10)
  5. Hypoxia Inducible Factor (11)
  6. Anti-angiogenic effect (12)
  7. Generation of 3-mercapto propionaldehyde (13)
  8. Other possible mechanisms : reduction of igf1 (14), inhibition of cox2 (15), intracellular red-ox-signal transduction-gene expression, collagen-extracellular matrix encapsulation (16)
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References :

  1. Bracke et al. 1999
  2. Prasad KD. Integr cancer Ther. 2004; 3:310-22
  3. Prasad et al , 1999
  4. Pathak et al.   J Am Coll Nutr. 2002;21:416-21
  5. Bland 1999;2001
  6. Malmberg KJ. Et al. Clin Cancer Res. 2002; 8:1772-8
  7. Roffe l, et al J Clin Oncol. 2004;22:4418-24
  8. Block et al.    Cancer Treatment Reviews. 2007; 33:407-418
  9. Chen Q et al PNSA. 2005; 102:13604-9
  10. Melanoma Res. 2006 Dec;1696):509-19
  11. Gao P et al.   Cancer Cell 2007; 12:230-8
  12. Mikirova N. et al J Transl Med. 2008; 6:50
  13. Toohey Jl.    Cancer Letters. 2008; 263:164-9
  14. Lee SK et al. J Cell Physiol 2008;216:180-8
  15. Catani MV et al.    Biochem J 2002; 364;441-7
  16. Cameron E. etal.   Int J Vitamin Nutr res; 1982:115-27