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Cytotoxic effects of selective serotonin‐ and serotonin‐norepinephrine reuptake inhibitors on human metastatic breast cancer cell line, MCF‐7 (842.3)
Author(s) -
Bavadekar Supriya,
Panchal Palak,
Hanbashi Ali,
Vansal Sandeep
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.842.3
Subject(s) - sertraline , venlafaxine , citalopram , escitalopram , pharmacology , serotonin uptake inhibitors , paroxetine , reuptake inhibitor , fluoxetine , chemistry , serotonin , medicine , antidepressant , receptor , hippocampus
Current evidence suggests that some antidepressants possess growth‐inhibitory effects against a number of cancer cell lines. The present study evaluated seven of the most commonly prescribed antidepressants in the US for cytotoxic effects on MCF‐7 breast cancer cells. These included selective serotonin reuptake inhibitors (sertraline, fluoxetine, paroxetine, citalopram, escitalopram) and serotonin‐norepinephrine reuptake inhibitors (venlafaxine, duloxetine). Viability was determined after 24 h using the XTT cell proliferation assay. All test agents inhibited cell growth in a concentration‐dependent manner. Sertraline (IC 50 ~16 µM) was the most potent, followed by equipotent paroxetine, duloxetine, and fluoxetine (IC 50 ~31‐36 µM), while citalopram, escitalopram, and venlafaxine were significantly weaker. The lead compound, sertraline, induced apoptosis, as evidenced by morphological changes, phosphatidylserine externalization, and poly(ADP‐ribose) polymerase (PARP) cleavage. Future experiments are aimed towards identifying the binding site(s) for sertraline and further elucidating the signal transduction pathway(s) involved in the cytotoxic effect. In summary, the high sensitivity shown by the four most potent agents, and especially sertraline, in inhibiting MCF‐7 growth suggests that these agents should be evaluated further for potential use in anti‐breast cancer therapy. Grant Funding Source : This work is supported by the Division of Pharmaceutical Sciences at Long Island University.