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Non-Small Cell Lung Cancer Treatment: insights from Ca2+ influx and channel activity
Non-small cell lung cancer (NSCLC) is the leading form of lung cancer and has been the focus of much research within the field of oncology. It is categorized by a ras mutation which makes it insensitive to treatment by known kinase inhibitors. This leaves cytotoxic drugs, surgery and radiation as the only effective means of treatment, but each of these presents its own limitations. In response to this, Viswanadha et al. (2010) have taken a look at the potentials of RP-3042, a novel and potent cytostatic agent that inhibits cell proliferation in NSCLS cell lines via a Calcium Released Activated Calcium (CRAC) channel pathway. The results of their study could have significant implications in future treatment efforts for NSCLC.
To conduct their study, Viswanadha et al loaded NCI-H460 cells with Fluo-8® AM, a novel green fluorescent indicator that monitors Ca2+ concentrations and influx. The versatility of this indicator allows researchers to test a variety of Ca2+ binding disassociation constants and also is less temperature dependent, which helps deliver more consistent and accurate results. Once these cells were loaded with this indicator, Viswanadha and his team inhibited thapsigargin induced calcium influx to observe the growth inhibiting effect of RP-3042 on different NSCLC cell lines such as A549, NCI-H460, and NCI-H522. The brightness and intensity of the Fluo-8 AM indicator allows researchers to easily observe the effect of RP-3042 as it worked through a Calcium Released Activated Calcium channel pathway. What the researches saw was the remarkable effect RP-3042 had on inhibiting thapsigargin-induced calcium influx into NCI-H460 cells. All cell lines under study displayed high levels of Orai1 and Stim1, which are two key proteins for calcium signaling via CRAC channels. Also, RP-3042 was found to be metabolically stable across all the species used in the study (mice, rats, dogs, monkeys and humans) and it showed no significant CYP inhibition in human liver microsomes. All of this further speaks to the validity of using RP-3042 in treatment of NSCLS.
In general, this study found that RP-3042 is effective and safe and as a result has a lot of promising potential in terms of treatment of NSCLC. This novel approach to treatment using the inhibition of CRAC channels has been made possible by researcher's ability to closely and carefully monitor Ca2+ influx and activity. The Fluo-8 AM indicator was essential to this process. It allows for an easier loading process, which reduces the chances of damaging the sample, which would diminish the integrity of the research. In a study like this, the activity of Ca2+ was the key indicator into determining the efficacy of RP-3042 in inhibiting NSCLC cell growth. Ensuring that the indicator being used to obtain the results was not interfering or hurting the sample being studied was a key factor that helped make this study possible. With new tools on their hands like Fluo-8 AM, researches are able to make novel discoveries that will help develop and test new treatments for some of the most damaging diseases.
To conduct their study, Viswanadha et al loaded NCI-H460 cells with Fluo-8® AM, a novel green fluorescent indicator that monitors Ca2+ concentrations and influx. The versatility of this indicator allows researchers to test a variety of Ca2+ binding disassociation constants and also is less temperature dependent, which helps deliver more consistent and accurate results. Once these cells were loaded with this indicator, Viswanadha and his team inhibited thapsigargin induced calcium influx to observe the growth inhibiting effect of RP-3042 on different NSCLC cell lines such as A549, NCI-H460, and NCI-H522. The brightness and intensity of the Fluo-8 AM indicator allows researchers to easily observe the effect of RP-3042 as it worked through a Calcium Released Activated Calcium channel pathway. What the researches saw was the remarkable effect RP-3042 had on inhibiting thapsigargin-induced calcium influx into NCI-H460 cells. All cell lines under study displayed high levels of Orai1 and Stim1, which are two key proteins for calcium signaling via CRAC channels. Also, RP-3042 was found to be metabolically stable across all the species used in the study (mice, rats, dogs, monkeys and humans) and it showed no significant CYP inhibition in human liver microsomes. All of this further speaks to the validity of using RP-3042 in treatment of NSCLS.
In general, this study found that RP-3042 is effective and safe and as a result has a lot of promising potential in terms of treatment of NSCLC. This novel approach to treatment using the inhibition of CRAC channels has been made possible by researcher's ability to closely and carefully monitor Ca2+ influx and activity. The Fluo-8 AM indicator was essential to this process. It allows for an easier loading process, which reduces the chances of damaging the sample, which would diminish the integrity of the research. In a study like this, the activity of Ca2+ was the key indicator into determining the efficacy of RP-3042 in inhibiting NSCLC cell growth. Ensuring that the indicator being used to obtain the results was not interfering or hurting the sample being studied was a key factor that helped make this study possible. With new tools on their hands like Fluo-8 AM, researches are able to make novel discoveries that will help develop and test new treatments for some of the most damaging diseases.
References
- Sumalatha Kuppireddi, Sridhar Veeraraghavan, Gayatri Swaroop Merikapudi and Swaroop Vakkalanka. Abstract LB-109: Pharmacological evaluation of RP3042, a cytostatic calcium release activated calcium (CRAC) channel inhibitor, in non-small cell lung cancer. Cancer Research (2010). DOI: 10.1158/1538-7445.AM10-LB-109
Original created on August 31, 2016, last updated on August 31, 2016
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