Avemar and Lymphoma
Oncol Rep. 2009 Mar;21(3):787-91.
Saiko P, Ozsvar-Kozma M, Graser G, Lackner A, Grusch M, Madlener S, Krupitza G, Jaeger W, Hidvegi M, Agarwal RP, Fritzer-Szekeres M, Szekeres T.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, A-1090 Vienna, Austria.
Avemar (MSC) is a nontoxic fermented wheat germ extract, which has been shown to significantly improve the survival rate in patients suffering from various malignancies. We investigated its effects in sensitive and 5-FdUrd/Ara-C cross-resistant H9 human lymphoma cells. After 48 and 72 h of incubation, Avemar inhibited the growth of sensitive H9 cells with IC50 values of 290 and 200 microg/ml, whereas the growth of 5-FdUrd/Ara-C cross-resistant H9 cells was attenuated with IC50 values of 180 and 145 microg/ml, respectively. Treatment with 300 microg/ml MSC for 48 h caused dose-dependent induction of apoptosis in 48% of sensitive H9 cells. In cross-resistant H9 cells, incubation with 200 microg/ml Avemar for 48 h led to 41% of apoptotic tumor cells. Growth arrest of sensitive H9 cells after exposure to various concentrations of MSC occurred mainly in the S phase of the cell cycle, thereby increasing the cell population from 54 to 73% while depleting cells in the G0-G1 phase from 40 to 19%. Growth arrest in cross-resistant H9 cells occurred also mainly in the S phase, increasing the cell population from 45 to 68% while depleting cells in the G0-G1 phase from 45 to 31%. As MSC treatment likely overcomes 5-FdUrd/Ara-C resistance, further investigations to elucidate the exact mechanisms are warranted. We conclude that Avemar exerts a number of beneficial effects which could support conventional chemotherapy of human malignancies.
PMID: 19212640 [PubMed - indexed for MEDLINE
The Cell Cycle and Cancer Drugs
Our body's cells -- both normal and cancerous -- make more cells like them through a series of four major steps often depicted as a circle, called the cell cycle. Most cancer drugs work by interfering with a specific step in the cell cycle, because if the cell cannot make it through the first three steps of the cell cycle, it cannot divide to make two more cells just like it in the fourth step of the cell cycle -- cell division. In that case, it usually will die, subtracting one cancer cell from the body's burden, and preventing two more from being created.
How Cancer Drugs Work -- Or Don't
The reason one cancer drug may work well on a particular cancer while a different drug may not is because drugs each typically have different ways of killing cancer cells, referred to as a drug's mechanism of action, and various cancers are more or less vulnerable to being attacked in any particular way.
If a patient's cancer doesn't respond to treatment with a particular drug, the cancer is said to be resistant to that drug, and doctors will usually select another drug that may work better.
The cancer drug 5-FdUrd is an improved version of the cancer drug 5-FU. It makes a sort of "counterfeit" uracil, a substance needed to make new RNA necessary for cell division. When cells try to use the counterfeit uracil, it doesn't work, so the cells can't make RNA. The cell quits moving through the cell cycle, and so it dies.
Ara-C is a cancer drug made to resemble a protein cells need to make DNA, but which won't work for that purpose. When cells take it up, they can't make DNA. Unable to make DNA, they can't move further through the cell cycle, and they die.
Sometimes, a patient's cancer will be resistant to not one, but two different cancer drugs that work in two different ways. Such a cancer is said to be "cross-resistant", meaning neither drug works, alone or in combination. A cancer like that can be very difficult to treat successfully.
Lymphoma is a cancer that starts in lymphocytes, white blood cells of the immune system. Among lymphoma cell types, some called H9 human lymphoma cells can be killed by FdUrd or Ara-C. But if they are cross-resistant to both drugs, the H9 lymphoma cells are an example of cancer cells very hard to kill.
However, in a recent research study of H9 cells cross-resistant to both drugs, an international team of cancer scientists working together from universities in the US and Europe found that a natural substance earlier shown effective against several other kinds of cancer killed cross-resistant H9 lymhoma cells when neither of the two conventional cancer drugs used against them in the study could do so.
Saiko P, Ozsvar-Kozma M, Graser G, Lackner A, Grusch M, Madlener S, Krupitza G, Jaeger W, Hidvegi M, Agarwal RP, Fritzer-Szekeres M, Szekeres T.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, A-1090 Vienna, Austria.
Avemar (MSC) is a nontoxic fermented wheat germ extract, which has been shown to significantly improve the survival rate in patients suffering from various malignancies. We investigated its effects in sensitive and 5-FdUrd/Ara-C cross-resistant H9 human lymphoma cells. After 48 and 72 h of incubation, Avemar inhibited the growth of sensitive H9 cells with IC50 values of 290 and 200 microg/ml, whereas the growth of 5-FdUrd/Ara-C cross-resistant H9 cells was attenuated with IC50 values of 180 and 145 microg/ml, respectively. Treatment with 300 microg/ml MSC for 48 h caused dose-dependent induction of apoptosis in 48% of sensitive H9 cells. In cross-resistant H9 cells, incubation with 200 microg/ml Avemar for 48 h led to 41% of apoptotic tumor cells. Growth arrest of sensitive H9 cells after exposure to various concentrations of MSC occurred mainly in the S phase of the cell cycle, thereby increasing the cell population from 54 to 73% while depleting cells in the G0-G1 phase from 40 to 19%. Growth arrest in cross-resistant H9 cells occurred also mainly in the S phase, increasing the cell population from 45 to 68% while depleting cells in the G0-G1 phase from 45 to 31%. As MSC treatment likely overcomes 5-FdUrd/Ara-C resistance, further investigations to elucidate the exact mechanisms are warranted. We conclude that Avemar exerts a number of beneficial effects which could support conventional chemotherapy of human malignancies.
PMID: 19212640 [PubMed - indexed for MEDLINE
The Cell Cycle and Cancer Drugs
Our body's cells -- both normal and cancerous -- make more cells like them through a series of four major steps often depicted as a circle, called the cell cycle. Most cancer drugs work by interfering with a specific step in the cell cycle, because if the cell cannot make it through the first three steps of the cell cycle, it cannot divide to make two more cells just like it in the fourth step of the cell cycle -- cell division. In that case, it usually will die, subtracting one cancer cell from the body's burden, and preventing two more from being created.
How Cancer Drugs Work -- Or Don't
The reason one cancer drug may work well on a particular cancer while a different drug may not is because drugs each typically have different ways of killing cancer cells, referred to as a drug's mechanism of action, and various cancers are more or less vulnerable to being attacked in any particular way.
If a patient's cancer doesn't respond to treatment with a particular drug, the cancer is said to be resistant to that drug, and doctors will usually select another drug that may work better.
The cancer drug 5-FdUrd is an improved version of the cancer drug 5-FU. It makes a sort of "counterfeit" uracil, a substance needed to make new RNA necessary for cell division. When cells try to use the counterfeit uracil, it doesn't work, so the cells can't make RNA. The cell quits moving through the cell cycle, and so it dies.
Ara-C is a cancer drug made to resemble a protein cells need to make DNA, but which won't work for that purpose. When cells take it up, they can't make DNA. Unable to make DNA, they can't move further through the cell cycle, and they die.
Sometimes, a patient's cancer will be resistant to not one, but two different cancer drugs that work in two different ways. Such a cancer is said to be "cross-resistant", meaning neither drug works, alone or in combination. A cancer like that can be very difficult to treat successfully.
Lymphoma is a cancer that starts in lymphocytes, white blood cells of the immune system. Among lymphoma cell types, some called H9 human lymphoma cells can be killed by FdUrd or Ara-C. But if they are cross-resistant to both drugs, the H9 lymphoma cells are an example of cancer cells very hard to kill.
However, in a recent research study of H9 cells cross-resistant to both drugs, an international team of cancer scientists working together from universities in the US and Europe found that a natural substance earlier shown effective against several other kinds of cancer killed cross-resistant H9 lymhoma cells when neither of the two conventional cancer drugs used against them in the study could do so.
posted by Dr Frank Ervolino | 8:32 PM
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