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My plant extract (ethyl acetate fraction) seems to have two different effects depending on the cell/cell line it's being tested on. On liver cancer cells (HepG2), it is moderately cytotoxic. But on lymphocytes and macrophages, it helps increase their proliferation. Is this really possible? What do you think is the possible explanation for this?

I've been trying to find studies that might have similar results as mine, but none so far. I found one study wherein their extract both exhibited anti-proliferative effects on both cancer cells and fibroblasts. However, the effect is much stronger on cancer cells.

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  • $\begingroup$ "I found one study wherein their extract both exhibited anti-proliferative effects on both cancer cells and fibroblasts" - Could you please cite that article? $\endgroup$
    – Chris Rogers
    Commented Aug 21, 2021 at 4:52
  • $\begingroup$ I couldn't find the study anymore (forgot to save it, I guess). But I found another one - similar results, wherein the extract had a lower level of toxicity against fibroblasts, compared to cancer cell lines: frontiersin.org/articles/10.3389/fphar.2017.00371/full $\endgroup$
    – Maria
    Commented Aug 22, 2021 at 3:42

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Of course different types of cells, or even the same type of cell in different conditions, may react differently to the same stimulus. Regarding your "plant extract", it likely has many different molecular components. A typical biochemistry way to investigate further would be to separate the extract into fractions containing different components, and see whether an effect can be prodced by one or more of the components and not others.

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  • $\begingroup$ Oh, actually, I used the ethyl acetate fraction. The hexane fraction is highly toxic based on my preliminary assays. I will edit my question to add this info, sorry for the missing info. $\endgroup$
    – Maria
    Commented Aug 22, 2021 at 3:35
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Cell lines can do wacky things

Have a look at Zhou, 2019, which discusses the genome of HepG2 cells. These typically have 49 to 52 chromosomes... and many other interesting aberrations. Awortwe, 2014 commented on the irreproducibility of drug-herb interaction studies in cell lines; they note Caco-2 cells could vary 100-fold in their ability to transport mannitol. Cell lines are frequently subject to genetic instability associated with their immortalization from a tumor, followed by in vitro evolution that changes their behavior. (Fusenig, 2017) The old traditional cell lines are useful in some contexts - if you would like to find a protein that binds something you are interested in, for example - but they can't be counted on to react in a human way.

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  • $\begingroup$ Thanks for the references. I would think the cell lines are useful for preliminary studies, like screening of plant extracts. I do primary cultures, I get murine macrophages and lymphocytes, since I want to screen for potential immunostimulants. My colleagues test their extracts on cancer cell lines. $\endgroup$
    – Maria
    Commented Aug 22, 2021 at 3:32
  • $\begingroup$ Finding a consistent interaction is useful. I imagine you could fractionate the extract and identify the compound that affects the HepG2 cells. Injected into a mouse, maybe it causes elevated liver enzymes ... maybe it cures liver cancer. :) Either way, it might be something that a person taking an herbal supplement would like to know about. $\endgroup$
    – Mike Serfas
    Commented Aug 23, 2021 at 10:27
  • $\begingroup$ True! I'm still screening but this plant extract can be one of the candidates for further elucidation. Thanks! $\endgroup$
    – Maria
    Commented Aug 24, 2021 at 6:24

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