Telomerase Antagonist Effective in all major breast cancer cell lines

[Lani]

ABSTRACT: Telomerase Template Antagonist GRN163L Disrupts Telomere Maintenance, Tumor Growth, and Metastasis of Breast Cancer [Clinical Cancer Research; Subscribe]
Purpose: Maintenance of telomeres by telomerase is critical for the continuing proliferation of most advanced cancer cells. Telomerase activity has been detected in the vast majority of cancer cells but not most normal cells, making the enzyme an attractive target for anticancer therapy. The aim of this study was to address the breast cancer translational potential of the novel telomerase inhibitor, GRN163L.

Experimental Design: In the present study, we investigated the effects of GRN163L treatment on a panel of breast cancer cells representing different tumor subtypes with varying genetic backgrounds, including ER+, ER-, HER2+, BRCA1 mutant breast tumor cells as well as doxorubicin-resistant cancer cells. To investigate the in vivo effects of GRN163L, we employed a breast cancer xenograft and metastasis model that simulates a clinical situation in which a patient arrives with a primary tumor that may be then treated or surgically removed.

Results: GRN163L effectively inhibited telomerase activity in a dose-dependent fashion in all breast cancer cell lines resulting in progressive telomere shortening. A mismatch control oligonucleotide showed no effect on telomerase activity and GRN163L did not significantly affect telomere shortening in normal human mammary epithelial cells or in endothelial cells. Breast cancer cells that exhibited telomerase inhibition also exhibited significant reduction in colony formation and tumorigenicity. Furthermore, GRN163L suppressed tumor growth and lung metastases (P = 0.017) of MDA-MB-231 cells in vivo after 4 weeks of treatment.

Conclusions: These results show in vivo effectiveness of GRN163L in breast cancer and support its promising clinical potential for breast cancer treatment.

[Tom]

Hi Lani.

I have been losing sleep over telomerase activity for many months now. I am concerned about the effects of alpha-lipoic acid on telomeres. Alpha-lipoic acid is fast becoming known as a substance that might be a fountain of youth of sorts, for cells, as it can prevent the normal shortening of the telomeres with each successive cell division. This has the potential, at some level, to make them immortal.

There is research that alpha-lipoic acid can promote apoptosis in malignant cells, but I can't help but wonder what the true effect might be if it is helping to sustain telomere length. Let me know what your thoughts are on this, as I have been giving Mom alpha-lipoic acid for some time now, and would hate to find out later that I am doing anything to aid tumor cell survival. Thanks.

Tom

[Lani]

My opinion is not worth anything as NOONE knows how this all really works. We are just beginning to get an inkling. I have seen videos of worms whose telomers hardly shorten with cell divisions and they look "young" and live longer. That is on an organism-sized basis rather than a cellular basis (it may not work uniformly within an organism if the enzyme is somewhat tissue specific) and worms and people may not work exactly the same (lets hope so!)

On a personal level, I am a cautious type and know some substances have totally different (and even opposite) effects depending on what concentration you use and in what environment you give them (eg. Faslodex when given in the presence of estrogen). Since noone knows, you are truly just rolling the dice--but the price of gambling is intolerably high.

Noone can decide for you/your mother. I just posted the information to get people thinking--each must decide what risks to take. This is the price of fighting a disease where more is unknown than known despite what seem to be our great leaps and bounds of late. Sorry I can not be of more help!

[Lani]

If you were a woman I would say you must decide whether to follow your instinct (woman's intuition) if it is causing you to lose sleep.

I have no idea how man's intuition works, or even if there is such a thing...

[R.B.]

Tom

Tom it seems to me that cancer reflects life - our real level of control is limited and somewhat illusory - we can only do our best.

Mercury and radiation were considered treatments many moons ago. We would now reagrd them as amusing but there were some seeds in there I suppose - primitive chemo and radio therapy which in turn will be smiled about by future generations with a greater understanding.



LANI


Intuition

A huge subject.

The brains ability to connect and compute at very subtle levels?.

Low level telepathy?.

Male? female? genetic? brain level function dependent? given?...............

Global consiousness? god gaia higher existence?

I am male and beleive in intution (however you define it) as a concept, and often let intution win out over strict "logic".

RB