 |
04-23-2007, 10:07 AM
|
#1
|
|
Senior Member
Join Date: Mar 2006
Posts: 4,778
|
STATINS induce apoptosis(cell suicide) of breast cancer cells (both ER+ and ER-)
neither cell line was her2+ however
ABSTRACT: Simvastatin induces apoptosis in human breast cancer cells: p53 and estrogen receptor independent pathway requiring signalling through JNK [Cancer Letters]
The effect of simvastatin, a widely used statin for the treatment of hypercholesterolemia, was investigated in the estrogen receptor (ER)-positive MCF-7, and the ER-negative MDA-MB 231 human breast cancer cell lines. Simvastatin induced cell cycle arrest and apoptosis in both cells. These effects of simvastatin were not altered by 17-?-estradiol treatment.
MCF-7 cells express wild-type tumor suppressor protein p53, whereas MDA-MB 231 cells carry a p53 mutation. However, no alteration in the level or localisation of p53 was observed with simvastatin treatment in either cell line. On the other hand, simvastatin strongly stimulated phosphorylation of c-jun which was completely abolished by the c-jun NH2-terminal kinase (JNK) inhibitor SP600125, which also significantly reduced the antiproliferative and apoptotic effects of simvastatin in these cells.
In conclusion, we describe here that simvastatin induces apoptosis via involvement of JNK in breast cancer cells independent of their ER or p53 expression status. These findings indicate a great potential for statins for the treatment of cancers resistant to currently used drugs, and target the JNK signalling pathway for a novel approach of breast cancer treatment.
|
|
|
|
04-23-2007, 10:13 AM
|
#2
|
|
Senior Member
Join Date: Jul 2005
Location: Ft. Collins, Colorado
Posts: 546
|
are there human trials
of statins in bc treatment that you know of? I'll look too, but I'm guessing not and that this information is based on in vitro studies. Thank you AGAIN for all of the good information that really keeps some of us going in the tough times. The service you provide, Lani, has tremendous impact!
__________________
with love and gratitude,
joy
dx stage I 2/2000*er/pr+; her- per IHC*lumpectomy*4 rounds A/C*30 rads*tamoxifen*dx stage 4 5/2002*huge mets to liver*tiny mets to lungs*stopped tamoxifen*5/02 taxotere/xeloda*her 2 checked with FiSH-her2+++herceptin *2/03 stopped chemo femara w/herceptin*zolodex*04 switched to aromasin w/herceptin*05 high estrogen tx*11/05taxol/carbo*7/06 stopped chemo; megace/herceptin*9/06navelbine/herceptin*5/07tykerb/xeloda great response*4/08 progression in liver; ooph/ faslodex /herceptin
6/08 began Herceptin DM-1
9/08 progression
|
|
|
|
|
04-23-2007, 10:18 AM
|
#3
|
|
Senior Member
Join Date: Mar 2006
Posts: 4,778
|
I believe UCSF had one which was reported at San Antonio in 2005
one name on the paper presented was Laura Esserman, MD the head of their cancer center.
Statins are widely used --side-effects are easily found (google them)
Haven't seen papers on statins with her2+ cells lines (will let you know if I find one)
|
|
|
|
|
04-23-2007, 10:32 AM
|
#4
|
|
Senior Member
Join Date: Mar 2006
Posts: 4,778
|
PS It is great to receive appreciative messages
from posters named "Joy" and "Hopeful"--that is the point!
|
|
|
|
|
04-23-2007, 03:36 PM
|
#5
|
|
Senior Member
Join Date: Sep 2005
Location: Naples FL
Posts: 1,744
|
That was interesting. I don't know how coincidental this is but 2 years before I was diagnosed with breast cancer my cholesterol went sky high. I had NO history of high cholesterol in my family (or of cancer either) and was slim and ate a low fat, low dairy diet. Tried natural cholesterol lowering strategies ( like oatmeal and cheerios!) but nothing worked. I wonder if there is a correlation between breast cancer and high cholesterol??? I started on lovastatin after I finished chemo...
__________________
 Suzan W.
age 54 at diagnosis
5/05 suspicious mammogram-left breast
5/05 biopsy-invasive lobular carcinoma with LCIS,8mm tumor,stage 1 grade 2, ER+ PR+ Her2+++
6/14/05 bilateral mastectomy, node neg. all scans neg.
Oncotype DX-high risk
8/05-10/05 4 rounds A/C
10/05 -10/06 1 yr. herceptin
arimidex-5 years
2/14/08 started daily self administered injections..FORTEO for severe osteoporosis
7/28/09 BRCA 1 negative BRCA2 POSITIVE
8/17/09 prophylactic salpingo-oophorectomy
10/15/10 last FORTEOinjection
RECLAST infusion(ostoeporosis)
6/14/10 5 year cancerversary!
8/2010-18%increase in bone density!
no further treatments
Oncologist says, "Go do the Happy Dance"
I say,"What a long strange trip its been"
'One day at a time'
6-14-2015. 10 YEAR CANCERVERSARY!
7-16 to 9-16. Extensive (and expensive) dental work done to save teeth. Damage from osteoporosis and chemo and long term bisphosphonate use
6-14-16. 11 YEAR CANCERVERSARY!!
7-20-16 Prolia injection for severe osteoporosis
2 days later, massive hive outbreak. This led to an eventual dx of Chronic Ideopathic Urticaria, an auto-immune disease from HELL.
6-14-17 12 YEAR CANCERVERSARY!!
still suffering from CIU. 4 hospitilizations in the past year
as of today, 10-31-17 in remission from CIU and still, CANCER FREE!!!
6-14-18 13 YEAR CANCERVERSARY!! NED!!
|
|
|
|
|
04-23-2007, 04:01 PM
|
#6
|
|
Senior Member
Join Date: Sep 2005
Location: Stockton, NJ
Posts: 4,179
|
As far as a possible cholesterol/bc connection we can go down 2 paths.
One is that cholesterol is the precursor to the manufacture of all sex hormones (estrogen, progesterone, androgens). It is one of the reasons the body manufactures cholesterol. Therefore, you could possibly make some sort of conclusion that more cholestrol, more estrogen etc. However..
before hormones are made, first prostagladins are made (and then the sex hormones are made from that). Well, if you get into all that RB has been teaching us on omega 3s and omega 6s, these fats feed into that pathway. Prostaglandins cause inflammation (which isn't a bad thing in general but can be bad if it is ongoing. For example, pain comes from an inflammatory response. It is a good thing so that you know you are hurt or sick but a bad thing if it goes on forever. Because long term inflammation causes tissue damage. Tissue damage can cause changes in tissue DNA (ie dysplasia or cancers).
So, some of these pathways can definitely be involved. You can see how complex it all is - even the cancer cell in general. Its just amazingly complex and formidable!!!
__________________
Kind regards
Becky
Found lump via BSE
Diagnosed 8/04 at age 45
1.9cm tumor, ER+PR-, Her2 3+(rt side)
2 micromets to sentinel node
Stage 2A
left 3mm DCIS - low grade ER+PR+Her2 neg
lumpectomies 9/7/04
4DD AC followed by 4 DD taxol
Used Leukine instead of Neulasta
35 rads on right side only
4/05 started Tamoxifen
Started Herceptin 4 months after last Taxol due to
trial results and 2005 ASCO meeting & recommendations
Oophorectomy 8/05
Started Arimidex 9/05
Finished Herceptin (16 months) 9/06
Arimidex Only
Prolia every 6 months for osteopenia
NED 18 years!
Said Christopher Robin to Pooh: "You must remember this: You're braver than you believe and stronger than you seem and smarter than you think"
|
|
|
|
|
04-23-2007, 05:00 PM
|
#7
|
|
Senior Member
Join Date: Jun 2006
Posts: 153
|
I was part of the UCSF study for statins and DCIS. I think it was a phase II or III not sure.
__________________
|
|
|
|
|
07-10-2007, 08:09 PM
|
#8
|
|
Senior Member
Join Date: May 2007
Location: DFW area (TX)
Posts: 431
|
What was the result of the UCSF study for statins and DCIS??
|
|
|
|
|
07-10-2007, 08:23 PM
|
#9
|
|
Senior Member
Join Date: Mar 2006
Posts: 4,778
|
some articles by L. Esserman on statins and bc
9:
Campbell MJ, Esserman LJ, Zhou Y, Shoemaker M, Lobo M, Borman E, Baehner F, Kumar AS, Adduci K, Marx C, Petricoin EF, Liotta LA, Winters M, Benz S, Benz CC.
Related Articles, Links
Breast cancer growth prevention by statins.
Cancer Res. 2006 Sep 1;66(17):8707-14.
PMID: 16951186 [PubMed - in process]
dexed for MEDLINE]
13:
Kumar AS, Benz CC, Esserman LJ.
Related Articles, Links
Clinical trials are required to prove the chemopreventive worth of statins.
Arch Intern Med. 2006 May 22;166(10):1143; author reply 1144. No abstract available.
PMID: 16717179 [PubMed - indexed for MEDLINE]
14:
Kumar AS, Campbell M, Benz CC, Esserman LJ.
Related Articles, Links
A call for clinical trials: lipophilic statins may prove effective in treatment and prevention of particular breast cancer subtypes.
J Clin Oncol. 2006 May 1;24(13):2127; author reply 2127-8. No abstract available.
PMID: 16648516 [PubMed - indexed for MEDLINE]
20:
Kumar AS, Esserman LJ.
Related Articles, Links
Statins: health-promoting agents show promise for breast cancer prevention.
Clin Breast Cancer. 2005 Dec;6(5):455-9. Review. No abstract available.
PMID: 16381630 [PubMed - indexed for MEDLINE]
|
|
|
|
Posting Rules
|
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts
HTML code is Off
|
|
|
All times are GMT -7. The time now is 10:39 PM.
|
Linear Mode
