I'm working with a lipid extract from a deep-sea marine sponge which gave interesting results against HTC-116 cell line. After fractionating, the most active fraction contains ceramides and glicolipids. I hope at some point I will have the answer to this. but I'm just wondering if someone have a clear idea about it, as publications go both ways.
Silvia, I've come across several fractions, from different sources, that showed bioactivity towards cancer cell lines and were composed mainly of glycolipids. But you'll have to continue your bioassay-guided approach until you can tell for sure, maybe you have a minor constituent that isn't a ceramide nor a glycolipid and is responsible for the activity.
Silvia, I have come across both classes of lipids as active in various assays in natural product extracts. Sometimes they have non-specific detergent like effects in biochemjcal assays. I don't recall however either of them being active in HCT-116 (I presume cytotoxicity assay?). I agree with the earlier post to keep going with the bioassay guided fractionation, as you could have trace amounts of highly potent compounds (i.e. polyethers such as halichondrins, known cytotoxics isolated from sponges). These also have potent in vitro activity, and in vivo activity in animal models. Good luck.
I've worked with marine samples (sponges, coral, bacteria, fungi) as well and have come across a few anticancer glycolipids. The general rule was to check the active fractions by NMR which would help to indicate if they were glycolipids or not. If they were glycolipids, it was unlikely that they would ever make or be made into viable drugs so they were often abandoned as suitable leads.
Ceramide it self may induce apoptosis(programmed cell death). So it reduces proliferation and growth of cancer cell.
And for the ones who are interested, the answer in this particular case is...neither. Some other fractions which we need now to clarify what kind of compound is, was the most active...
That's why we love to do what we do :)
You chase down one promising lead only to find out you've been going down the wrong path. Hopefully though, you gain new knowledge and enjoy the journey even if it drove you a little crazy. All the best in your journey.
I would follow up with the glycolipid fraction. Ceramides can cause cell apoptosis by binding via FAS death domain. I disagree with the opinion that glycolipids cannot be developed into drugs. The advantage that glycolipids have over ceramides is their sugar polar heads which provides for their immune-related biological activities. Their non-specific detergent effect causing cell lysis occurs at and around CMC (critical micelle concentration). Look for specific acitivities in the lower concentration ranges. Good luck!
Dear Silvia gangliosides are known to be' overexpressed in colon cancer so i think that the gangliosides you recovered in your extract cold work interfiring with processes mediated by gangliosides in your cell line.
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