Possible Interaction: Melatonin and Tamoxifen

“Preliminary data would suggest that the pineal hormone, melatonin (MLT), may enhance tamoxifen (TMX) anti-tumour efficacy.”

“This phase II study would suggest that the neuroendocrine combination with TMX plus MLT may have some benefit in untreatable metastatic solid tumour patients, either in controlling cancer cell proliferation or improving the PS.”

“Co-treatment of the cells with melatonin loaded nanoparticles and tamoxifen caused two fold increase in the percentage of apoptosis (p<0.05).”

“Only 371 ng/mL tamoxifen caused a 38% growth inhibition of cells pre-exposed to vehicle whereas all concentrations of tamoxifen inhibited the growth of melatonin pre-exposed cells by 28% to 61% in a dose-dependent manner.”

“These results indicate that melatonin has the capability to augment the inhibitory actions of tamoxifen , and to a lesser extent itself, on human breast cancer cell growth.”

“Finally, we show that the inhibitory effect of tamoxifen (25 μM) is markedly enhanced by the coincubation with melatonin (1.3 mM) up to 75% (P < 0.001).”

“These data show that the antiproliferative effects of tamoxifen and ethanol, respectively, on mouse hepatoma cell line HEPA 1–6 are enhanced by melatonin.”

“Although the melatonin plus tamoxifen group had higher multiploidy percentage (38%), the difference was not statistically significant as compared to the tamoxifen (or melatonin) groups.”

“Moreover, tamoxifen (50–200 μm) in the presence of melatonin reduced basal membrane fluidity and MDA+4-HDA levels in microsomes.”

“These synergistic effects of tamoxifen and melatonin in stabilizing biological membranes may be important in protecting membranes from free radical damage.”

“Thus, the IC50s for preventing membrane rigidity and for inhibiting lipid peroxidation obtained for tamoxifen in the presence of melatonin were lower than those obtained with tamoxifen alone.”

“When melatonin was added, the efficacy of tamoxifen in preventing membrane rigidity was enhanced.”

“In particular, it has been demonstrated that MLT may stimulate estrogen receptor (ER) expression and enhance tamoxifen (TMX) effects other than the antiestrogenic action.”

“Moreover, the percent of survival at 1 year was significantly higher in patients treated with TMX plus MLT than in those treated with TMX alone (12/19 vs 5/21, p<0.01).”

“Therefore, MLT could amplify the efficacy of TMX also in patients with negative ER.”