I’d like to test DHA and any potential hits from the compounds in wormwood first in p52 mutants, since this mutation alters a tumor suppressor gene and is found in many varieties of cancer cells. Testing in this mutant type and a few others may be useful in predicting how these compounds will perform in tumors compared to healthy cells. From there, we may choose other mutants which could reveal which mutations make the cells more or less vulnerable to these compounds.
What are some specific future experiments scientists could perform in order to investgate and continue studying the radiosensitizing effects of DHA and wormwood?
In our future directions, we have a couple next steps for DHA. First, we’d like to repeat our experiment and expand the drug response curve with a larger range of final doses in food, from around 0.01mM to 10mM, since the quantify of DHA available limited our maximum tested dose to a lower quantity than the highest relevant dose. Knowing the response at the maximum physiologically relevant dose and having enough samples to establish statistical significance will help us understand if DHA merits further investigation in relevant mutant Drosophila melanogaster lines or cancer cell lines. Increasing the granularity at the lower doses will demonstrate whether the dose response curve has a u-shape (greater effect and mortality of tumor model at low AND high doses) or a step down effect with greater fly mortality occurring at higher doses.
However, directionally comparing with wormwood may reveal that DHA or another compound within wormwood has a greater effect when interacting with other compounds. This informs the future directions recommendation for wormwood. First, we would repeat the experiment with wild type and possibly p52 mutant Drosophila melanogaster, testing wormwood as a whole compound and using experimental matrix comparing the individual effects of active compounds in wormwood to the combined effects to identify any interactions. Identifying potential synergies or impedance of radiosensitizing effects of the whole compound allows us to select compounds of interest for future study as potential radiosensitizing chemotherapies. Radioprotectants which may impede the effect can be removed or used for other purposes. Then a drug response curve where response to further dilutions should also be included for the compound to establish the therapeutic index.
What are some specific future experiments scientists could perform in order to investigate and continue studying the radiosensitizing effects of DHA and wormwood?
Thanks for asking, Tenzin. In previous studies DHA has been shown as a potential radiosensitizer or compound which increases vulnerability to radiotherapy. It does this by reducing the cell’s time in the S-phase, the cell cycle which is least vulnerable to radiation. So far, DHA has been tested in cancer cell lines but not yet in heterogenous in vivo tests like this one in Drosophila Melanogaster. For this reason, we wanted to link our experiment to existing research with a promising radiosensitizer and also study its source, wormwood, to see if other compounds within the natural source could be interacting with DHA and reveal a possible better combination to investigate further.
Thanks for asking me to clarify. DHA is the active metabolite of artemisinin which is found in wormwood. This means that DHA is the active form of artemisinin which acts on cells in the body after artemisinin has been metabolized by the body.
What types of mutants would you like to test your compound on in the future and what would you like to learn from this?
Thanks for the interesting question, Nicole!
I’d like to test DHA and any potential hits from the compounds in wormwood first in p52 mutants, since this mutation alters a tumor suppressor gene and is found in many varieties of cancer cells. Testing in this mutant type and a few others may be useful in predicting how these compounds will perform in tumors compared to healthy cells. From there, we may choose other mutants which could reveal which mutations make the cells more or less vulnerable to these compounds.
What are some specific future experiments scientists could perform in order to investgate and continue studying the radiosensitizing effects of DHA and wormwood?
Thanks for the question, Jenny.
In our future directions, we have a couple next steps for DHA. First, we’d like to repeat our experiment and expand the drug response curve with a larger range of final doses in food, from around 0.01mM to 10mM, since the quantify of DHA available limited our maximum tested dose to a lower quantity than the highest relevant dose. Knowing the response at the maximum physiologically relevant dose and having enough samples to establish statistical significance will help us understand if DHA merits further investigation in relevant mutant Drosophila melanogaster lines or cancer cell lines. Increasing the granularity at the lower doses will demonstrate whether the dose response curve has a u-shape (greater effect and mortality of tumor model at low AND high doses) or a step down effect with greater fly mortality occurring at higher doses.
However, directionally comparing with wormwood may reveal that DHA or another compound within wormwood has a greater effect when interacting with other compounds. This informs the future directions recommendation for wormwood. First, we would repeat the experiment with wild type and possibly p52 mutant Drosophila melanogaster, testing wormwood as a whole compound and using experimental matrix comparing the individual effects of active compounds in wormwood to the combined effects to identify any interactions. Identifying potential synergies or impedance of radiosensitizing effects of the whole compound allows us to select compounds of interest for future study as potential radiosensitizing chemotherapies. Radioprotectants which may impede the effect can be removed or used for other purposes. Then a drug response curve where response to further dilutions should also be included for the compound to establish the therapeutic index.
What are some specific future experiments scientists could perform in order to investigate and continue studying the radiosensitizing effects of DHA and wormwood?
What made you initially choose DHA as a potential candidate for cancer therapy?
Thanks for asking, Tenzin. In previous studies DHA has been shown as a potential radiosensitizer or compound which increases vulnerability to radiotherapy. It does this by reducing the cell’s time in the S-phase, the cell cycle which is least vulnerable to radiation. So far, DHA has been tested in cancer cell lines but not yet in heterogenous in vivo tests like this one in Drosophila Melanogaster. For this reason, we wanted to link our experiment to existing research with a promising radiosensitizer and also study its source, wormwood, to see if other compounds within the natural source could be interacting with DHA and reveal a possible better combination to investigate further.
Sorry, I meant to type the cell cycle phase in which cells are least vulnerable to radiation.
What is the relationship between DHA and wormwood? Is DHA a compound that’s present within wormwood?
Thanks for asking me to clarify. DHA is the active metabolite of artemisinin which is found in wormwood. This means that DHA is the active form of artemisinin which acts on cells in the body after artemisinin has been metabolized by the body.