MetaVi Labs has automated the assay that was first used to measure the effect of inhibitory substances on migrating tumor cells.

Time-lapse Movies of Propranolol (beta-blocker) Treated Breast Cancer Cells

These are time-lapse movies of untreated and Propranolol treated cells. You can observe the dramatic difference in cell migration over an 10-hour period. The video below are un-treated mda-mb-231 cells over 10 hours in a 3D Collagen matrix. The video is Propranolol treated mda-mb-231 cells over 10 hours in a 3D Collagen matrix. Have a … Continue reading


SUMMARY

Beta-blocker use has been shown to reduce metastasis formation and extend life in seven cancer types: colon, mammary, melanoma, ovarian, prostate, non-small cell lung, hepatocellular.

Earlier use of beta-blockers increases efficacy, but improvement in lifespan can be seen at nearly every stage of cancer when used in combination with conventional treatment.

Patients at heightened risk of cancer and patients in remission could be optimal candidates for beta-blocker use as a cancer prophylactic.

Any clinically given dosage seems to be effective, whereas unselective beta-blockers (e.g. propranolol) are more effective than cardioselective beta-blockers (e.g. atenolol). Propranolol use drops the five-year cumulative probability of breast cancer-specific mortality from 26.8% to 9.4% [8].

Details

More than 90% of cancer deaths are caused by metastasis formation rather than the primary tumor [1]. Active migration of tumor cells is an essential prerequisite for invasion and metastasis formation. Norepinephrine is the most potent activator of cell migration as evidenced in colonic [2,20], mammary [3], and prostate [4] cancer cells. This increase is mediated predominantly by beta-2 adrenergic receptors and can therefore be inhibited by clinically established non-selective beta-blockers such as propranolol. The in vivo relevance of these experimental results was confirmed by mice xenograft models using prostate [5] and breast cancer [6]. Most strikingly, retrospective analyses of data from patients with several types of cancer showed that beta-blockers significantly reduce metastasis formation and consequently prolong the survival time of these patients. Results were obtained in epidemiological studies on breast cancer [7-10], melanoma [11-13], ovarian cancer [14], prostate cancer [15, 16], non-small cell lung cancer [17], and hepatocellular cancer [18] patients. Furthermore, a meta-analysis of these studies provided evidence that the use of beta-blockers can be associated with the prolonged survival of cancer patients, especially in patients with early-stage cancer treated primarily with surgery [19].

REFERENCES

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2. Masur K, Niggemann B, Zänker KS, Entschladen F. Norepinephrine-induced migration of SW 480 colon carcinoma cells is inhibited by beta-blockers. Cancer Res 2001; 61: 2866-2869.

3. Drell TL, Joseph J, Lang K, Niggemann B, Zänker KS, Entschladen F. Effects of neurotransmitters on the chemokinesis and chemotaxis of MDA-MB-468 human breast carcinoma cells. Breast Cancer Res Treat 2003; 80: 63-70.

4. Lang K, Drell TL, Lindecke A, Niggemann B, Kaltschmidt C, Zänker KS, Entschladen F. Induction of a metastatogenic tumor cell type by neurotransmitters and its pharmacological inhibition by established drugs. Int J Cancer 2004; 112: 231-238.

5. Palm D, Lang K, Niggemann B, Drell TL, Masur K, Zänker KS, Entschladen F. The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by beta-blockers. Int J Cancer 2006; 118: 2744-2749.

6. Sloan EK, Priceman SJ, Cox BF, Yu S, Pimentel MA, Tangkanangnukul V, Arevalo JM, Morizono K, Karanikolas BD, Wu L, Sood AK, Cole SW. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res 2010; 70: 7042-7052.

7. Powe DG, Voss MJ, Zänker KS, Habashi HO, Green AR, Ellis IO, Entschladen F. Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival. Oncotarget 2010; 1: 628-638.

8. Barron TI, Connolly RM, Sharp L, Bennett K, Visvanathan K. Beta Blockers and Breast Cancer Mortality: A Population-Based Study. J Clin Oncol 2011; 29: 2635-2644.

9. Melhem-Bertrandt A, Chavez-Macgregor M, Lei X, Brown EN, Lee RT, Meric-Bernstam F, Sood AK, Conzen SD, Hortobagyi GN, Gonzalez-Angulo AM. Beta-blocker use is associated with improved relapse-free survival in patients with triple-negative breast cancer. J Clin Oncol 2011; 29: 2645-2652.

10. Botteri E, Munzone E, Rotmensz N, Cipolla C, De Giorgi V, Santillo B, Zanelotti A, Adamoli L, Colleoni M, Viale G, Goldhirsch A, Gandini S. Therapeutic effect of β-blockers in triple-negative breast cancer postmenopausal women. Breast Cancer Res Treat 2013; 140: 567-75.

11. De Giorgi V, Grazzini M, Gandini S, Benemei S, Lotti T, Marchionni N, Geppetti P. Treatment with beta-blockers and reduced disease progression in patients with thick melanoma. Arch Intern Med 2011; 171: 779-781.

12. Lemeshow S, Sorensen HT, Phillips G, Yang EV, Antonsen S, Riis AH, Lesinski GB, Jackson R, Glaser R. beta-Blockers and survival among Danish patients with malignant melanoma: a population-based cohort study. Cancer Epidemiol Biomarkers Prev 2011; 20: 2273-2279.

13. De Giorgi V, Gandini S, Grazzini M, Benemei S, Marchionni N, Geppetti P. Effect of β-Blockers and Other Antihypertensive Drugs On the Risk of Melanoma Recurrence and Death. Mayo Clin Proc 2013; 88: 1196-203.

14. Diaz ES, Karlan BY, Li AJ. Impact of beta-blockers on epithelial ovarian cancer survival. Gynecol Oncol 2012; 127: 375-378.

15. Grytli HH, Fagerland MW, Fosså SD, Taskén KA, Håheim LL. Use of beta-blockers is associated with prostate cancer-specific survival in prostate cancer patients on androgen deprivation therapy. Prostate 2012; 73: 250-260.

16. Grytli HH, Fagerland MW, Fosså SD, Taskén KA. Association between the use of beta-blockers and prostate cancer-specific survival: a cohort study of 3561 prostate cancer patients with high-risk or metastatic disease. Eur Urol 2014; 65: 635-641.

17. Wang HM, Liao ZX, Komaki R, Welsh JW, O'Reilly MS, Chang JY, Zhuang Y, Levy LB, Lu C, Gomez DR. Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy. Ann Oncol 2013; 24: 1312-1319.

18. Nkontchou G, Aout M, Mahmoudi A, Roulot D, Bourcier V, Grando-Lemaire V, Ganne-Carrie N, Trinchet JC, Vicaut E, Beaugrand M. Effect of long-term propranolol treatment on hepatocellular carcinoma incidence in patients with HCV-associated cirrhosis. Cancer Prev Res (Phila) 2012; 5: 1007-14.

19. Choi CH, Song T, Kim TH, Choi JK, Park JY, Yoon A, Lee YY, Kim TJ, Bae DS, Lee JW, Kim BG. Meta-analysis of the effects of beta-blocker on survival time in cancer patients. J Cancer Res Clin Oncol. 2014, 140: 1179-1188.

20. Jansen, L.; Hoffmeister, M.; Arndt, V.; Chang-Claude, J.; Brenner, H. Stage-specific associations between beta-blocker use and prognosis after colorectal cancer. Cancer 2014, 120, 1178–1186.