Cancer cells escape chemo induced cell death

Cancer cells escape chemo induced cell death

Scientists found that cancer cells were able to escape the programmed cell death induced by chemotherapy once the chemicals were removed: in fact even though the normal cell death process had started, they were able to recover, as long as they did not go beyond the end stage of normal "apoptosis", the natural process through which cells kill themselves when they receive a signal to do so.

The study is the work of researchers from the Chinese University of Hong Kong and was published in the advanced online issue of the British Journal of Cancer on 16 December 2008.

The researchers treated a range of human cancer cell lines seeded on tissue culture plates with three chemicals known to trigger apoptosis to see if they could survive beyond the point of no return for normal cell death.

The cells came from cervical, skin, liver and breast cancer tumors. The three apoptotic chemicals were: jasplakinolide (Invitrogen), staurosporine (Sigma) and ethanol (Scharlau).

The researchers found that while the chemicals sent the right signals to trigger programmed cell death, if they were removed before the natural point of no return was reached, the cancer cells recovered: they regained their shape, function, and ability to replicate.

The point of no return beyond which the cells were not able to recover when the chemicals were removed, was when the nuclei of the cells had started to disintegrate. This event occurs right at the end of normal cell apoptosis.

The researchers concluded that:

"Our findings show that cancer cells can survive after initiation of apoptosis, thereby revealing an unexpected potential escape mechanism of cancer cells from chemotherapy."

Corresponding author Professor Ming-Chiu Fung, who is based at The Department of Biology at The Chinese University of Hong Kong, said:

"We have shown that various cancer cell lines can survive programmed cell death."

"This research suggests the existence of an escape tactic which cancer cells might call upon to survive chemotherapy treatment," added Fung.

Fung explained that these findings open the door to new avenues of research that will look into what drives these cancer cells to regain their full function and ability to replicate after chemotherapy. Also, we need to know more about the extent to which their ability to recover and continue to replicate helps them divide and grow during cycles of anti-cancer treatment, said Fung.

"Answers to these questions will provide potential new therapeutic targets in our battle against cancer," added Fung.

Information director for Cancer Research UK, Lesley Walker, said:

"This eye-opening discovery has created an entire map of new routes to explore in the search for new therapy targets. It is an intriguing advance and one that we hope will play a useful part in our efforts to beat cancer."

Apoptosis or programmed cell death is characterised by mitochondrial fragmentation and dysfunction, nuclear condensation, cytoplasmic shrinkage and activation of certain suicide proteins that also serve as useful markers that the process is under way.

"Reversibility of apoptosis in cancer cells".

H L Tang, K L Yuen, H M Tang, M C Fung.

British Journal of Cancer Advance online publication, 16 Dec 2008.

doi: 10.1038/sj.bjc.6604802

Click here for Abstract.

Sources: Journal article, Cancer Research UK.

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Section Issues On Medicine: Disease