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Licensed Unlicensed Requires Authentication Published by De Gruyter February 24, 2020

Polyamine stimulation perturbs intracellular Ca2+ homeostasis and decreases viability of breast cancer BT474 cells

Louis W.C. Chow , Kar-Lok Wong , Lian-Ru Shiao , King-Chuen Wu EMAIL logo and Yuk-Man Leung EMAIL logo


Intracellular polyamines such as spermine and spermidine are essential to cell growth in normal and especially in cancer cells. However, whether extracellular polyamines affect cancer cell survival is unknown. We therefore examined the actions of extracellular polyamines on breast cancer BT474 cells. Our data showed that spermine, spermidine, and putrescine decreased cell viability by apoptosis. These polyamines also elicited Ca2+ signals, but the latter were unlikely triggered via Ca2+-sensing receptor (CaSR) as BT474 cells have been demonstrated previously to lack CaSR expression. Spermine-elicited Ca2+ response composed of both Ca2+ release and Ca2+ influx. Spermine caused a complete discharge of the cyclopiazonic acid (CPA)-sensitive Ca2+ pool and, expectedly, endoplasmic reticulum (ER) stress. The Ca2+ influx pore opened by spermine was Mn2+-impermeable, distinct from the CPA-triggered store-operated Ca2+ channel, which was Mn2+-permeable. Spermine cytotoxic effects were not due to oxidative stress, as spermine did not trigger reactive oxygen species formation. Our results therefore suggest that spermine acted on a putative polyamine receptor in BT474 cells, causing cytotoxicity by Ca2+ overload, Ca2+ store depletion, and ER stress.


Y.M.L. would like to thank China Medical University, Taiwan, for providing funding (CMU108-S-31, CMU107-S-01). L.W.C.C. would like to thank the Macau Science and Technology Development Fund (FUNDO PARA O DESENVOLVIMENTO DAS CIÊNCIAS E DA TECNOLOGIA) for support (grant number 002/2015/A1). K.C.W. thanks the Chang Gung Memorial Hospital, Chiayi, for support (CMRPG6J0371, CMRPG6G0541).

  1. Conflict of interests: The authors declare no conflict of interests.

  2. Ethical approval: No humans or animals were used in this study; only cell lines were used in this work, and therefore, ethical approval is not required.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2019-06-23
Revised: 2020-01-06
Accepted: 2020-01-21
Published Online: 2020-02-24
Published in Print: 2020-03-26

©2020 Walter de Gruyter GmbH, Berlin/Boston

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