Each daughter cell may then reenter the division cycle (at G1) or may pass into a nonproliferative state (G0). As the length of the cell cycle increases, it is the duration of G1 that increases, while S, G2 and M remain constant.

While it may appear that we want to delay the entry of cancer cells into the cell cycle, this is NOT true for cells that are being subjected to cytotoxic treatment. In those cases, we WANT the cells to divide rapidly. The reason is that most anticancer agents cannot kill them unless they are rapidly and frequently dividing.

Conventional anticancer agents do the following:

a. Block the synthesis of DNA precursors
b. Damage the integrity of DNA
c. Interfere with DNA replication
d. Separate the two strands of DNA after replication
e. Interfere with function of mitotic spindle

Cancer cells have "highly evolved" mechanisms to prevent lipid peroxidation. But excess ROS causes oxidative stress which results lipid peroxidation in cancer cells (as well as normal cells). This prolongs the G1 phase and may result in cells entering the dormant G0 phase. Thus, excess ROS ("free radicals") interfere with the cytotoxic effects of antineoplastic agents on cancer cells by interfering with a cancer cell's progression through its cell cycle. Tumor cells in G0 are unaffected by chemotherapy and can usually reenter the division cycle after chemotherapy is completed. They can also repair damage done by drugs that do not require ongoing DNA synthesis (such as cisplatin).

Since anticancer drugs are effectively ONLY when cells are proliferating rapidly, it stands to reason that oxidative stress, which slows or arrests cell growth, interferes with the effectiveness of chemotherapy. It also explains why slow-growing tumors (such as lung or colon) are relatively unresponsive to chemotherapy.

Vitamin E is the main mechanism that cancer cells use to prevent lipid peroxidation. However, excessive oxidative stress may overcome even this highly evolved system, result in inhibition of cancer cell proliferation, and interfere with antineoplastic agents. ROS, contrary to being the mechanism by which anticancer agents kill cancer cells, prevent these agents from killing the cells.

The solution is to give the patient vitamin E, vitamin C and other selective antioxidants during chemotherapy. This will prevent the cancer cell from becoming dormant and thus expose it to the cytotoxic effects of the drugs.

Cancer itself causes oxidative stress. This has been experimentally demonstrated. In patients, oxidative stress is often compounded by poor nutrition. Tumor cells are usually able to overcome the oxidative stress of the condition and to proliferate rapidly. In fact, ROS damage to the host accelerate the promotion and progression of cancer.

However, administration of anticancer agents results in a much greater degree of ROS than cancer itself. This high level of ROS during chemotherapy may overcome the antioxidant defenses of cancer cells, which may result in that lipid peroxides reduce or halt cancer cell proliferation and thereby interfere with chemotherapeutic agents. Therefore, individuals with a relatively impaired antioxidant status are relatively unresponsive to chemotherapy.

On the contrary, supportive nutritional threapy with antioxidants during chemotherapy.may overcome the growth-inhibiting effects of oxidative stress and maintain responsiveness to anti-neoplastic agents" (Conklin 2000).

Can dietary supplements with antioxidants interfere with the mechanism whereby antineoplastic agents are cytotoxic to cancer cells. According to Conklin, "This is unlikely, since ROS are not involved in the mechanism of action of most anticancer drugs in current use." Bleomycin is an exception to the rule. However, although it is true that the scission of DNA by bleomycin does involved ROS, it also requires the presence of an electron donor. This is a function that can be fulfilled by certain antioxidants.

Conklin reviews the use of the following antioxidants and adds several dozen articles that were new to me. (My own literature search turned up about 150 articles showing the benefit of concurrent use.) The nutrients he discusses, in a mainly positive fashion, are:

Vitamin E
Vitamin C
Coenzyme Q10
B-carotene
GSH and glutathione esters
NAC
Glutamine
Selenium
Genistein and Daidzein
Quercetin

 

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