some article describes that more than one way of cell death (necrosis, autophagy, apoptosis) could possible in cells with single concentration of drug. How it is possible? how can single concentration of drug induce these types of cell death?
Even a single drug can induce several types of cell death. When the mitochondrial inner membrane is damaged, changed membrane potential would induce necrosis. On the other hand, when the mitochondrial outer membrane is damaged, leaked cytochrome c would induce apoptosis. This is shown in the following literature.
Article Identification of a novel compound that inhibits both mitoch...
I suscribe Dr Yoshida's answer. The same drug may produce different types of cellular death. Usually this is dose dependent. But in certain cases, like the one commented here, it may happen with the same dose.
It has not been found yet the exact biochemical or molecular relation between different types of cell death, but it is highly possible that there are interconnecting pathways. This remains to be elucidated in the future.
Thank you Dr. Yoshida & Dr. Tomas. Once cells undergone apoptosis it will die, then how it is possible to enter into the necrosis pathway. In my work, I checked apoptotic markers such as Bax, PARP, Caspase and anti-apoptotic Bcl-2 & inflammatory proteins such as TNF-a, Cox-2 & iNOS. I got good results in both. Leakage of inflammatory proteins indicates that drug induces necrosis & it also induces apoptosis. I used single concentration of drug with same tissue samples. How can I justify that?
Perhaps not the answer you are looking for, but in addition to previous pertinent answers, I would like to point out that we must keep in mind that sometimes apoptosis leads to secondary necrosis. Consequently, for the same drug at the same concentration in the same cell, even, you could observe both apoptosis in the earlier stages of cell death, then necrosis, secondary to apoptosis. Hence, the time at which cell death is observed after the toxic treatment must also be taken into account when qualifying the different types of cell death.
http://www.ncbi.nlm.nih.gov/pubmed/20974143
Actually this is a quite good question.Indeed a drug at the same concentration may cause not only apoptosis(programmed cell death) but also necrosis or autophagy in certain conditions. And the above phenomenon may be validated by flow cytometry and other methods such as western blotting, because when it comes to necrosis or necroptosis, only a small proportion of cancer cells undergo early-phase apoptosis(FITC-Annexin-Ⅴ positive cells ) and most of the cells are going to be located in the right upper quadrant. And I would like to say that apoptosis, necrosis and autophagy are closely related with each other.
Recently I have used an Bcl-2 family inhibitor Obatoclax in our current work and found that this drug was able to induce apoptosis and necrosis at the same time , because it could affect the MOMP and lysosome stability at the same time, the former effect could induce the loss of MOMP and the latter effect may affect the observed necrosis.
It may also be a timing issue. In cell culture, cells can undergo what's known as secondary necrosis. The cell will die through apoptosis and then eventually release all of its contents into the media. It's likely due to the fact that there are no mechanisms (ie. macrophages) to remove them http://www.ncbi.nlm.nih.gov/pubmed/20974143.
For realization apoptosis (process of elimination eukaryote cell with minimum entropy increase) it is need energy and molecular mechanism for it realization. If energy source or mechanism is destroyed partly, we can see ”pro inflammatory” apoptosis with “altered morphology”. If destruction more serious, to collapse of cell (break up it to parts without the any orderliness - necrosis) will lead more lately (then apoptosis). For UV induced apoptosis you can see it on webinar “Molecular Diagnostic” 6 -7 April 16 - (Non-monotonic dose dependence of UVB –induced apoptosis) and more carefully on webinar “Clinical Diagnostic” 2-3 October 16
In apoptosis resident macrophages-like cells clears dying cells and debris by engulfing them but that's not the case in necrosis,then how can one get markers for both apoptosis and necrosis?Then is it something time dependent?
A drug at the same concentration may cause not only apoptosis(programmed cell death) but also necrosis or autophagy in certain conditions. And the above phenomenon may be validated by flow cytometry and other methods such as western blotting, because when it comes to necrosis or necroptosis, only a small proportion of cancer cells undergo early-phase apoptosis(FITC-Annexin-Ⅴ positive cells ) and most of the cells are going to be located in the right upper quadrant. And I would like to say that apoptosis, necrosis and autophagy are closely related with each other.
Kunal Pal, you simply copied again. Weijun Wei wrote the following...
"a drug at the same concentration may cause not only apoptosis(programmed cell death) but also necrosis or autophagy in certain conditions. And the above phenomenon may be validated by flow cytometry and other methods such as western blotting, because when it comes to necrosis or necroptosis, only a small proportion of cancer cells undergo early-phase apoptosis(FITC-Annexin-Ⅴ positive cells ) and most of the cells are going to be located in the right upper quadrant. And I would like to say that apoptosis, necrosis and autophagy are closely related with each other."
Kunal, that is exactly what you wrote, or should I say, copied.
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