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

Abstract

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.

Putrescine Upregulates Melanogenesis Through Modulation of MITF Transcription Factor in B16F1 Mouse Melanoma Cells

“…To further investigate the potential toxicity of putrescine, putrescine concentrations of 0.25 to 2 mM were used to evaluate its effect on melanogenesis, but no evidence of cell death was observed. However, at concentrations above 10 mM, putrescine enhances cytotoxicity by considerably reducing cell viability of BT474 breast cancer cells, as shown in an earlier study ( 27 ). Decomposition of H 2 O 2 can produce hydroxyl radicals, which can cause DNA damage and trigger lipid peroxidation ( 28 ).…”

“…Tyrosinase is a key enzyme in the process of melanogenesis and a critical diagnostic tool for identifying the enzyme in the melanin synthesis pathway ( 23 ). Commonly used to enhance skin tone and cure dermatoses, tyrosinase inhibitors may effectively suppress the formation of the pigment ( 24 ). The purpose of the tyrosinase activity test was to assess the function of putrescine in melanin synthesis.…”

The Potential Role of Spermine and Its Acetylated Derivative in Human Malignancies

“…The effects of extracellular spermines on the breast cancer cell line BT474 were tested, which showed that spermine elicited a Ca 2+ signaling composed of both Ca 2+ release and Ca 2+ influx and could decrease cell line viability by apoptosis. This suggested spermine cytotoxicity could act through another in vitro mechanism, i.e., acting on a putative polyamine receptor in BT474 cells instead of oxidative stress, resulted in Ca 2+ overload, Ca 2+ store depletion and ER stress [45]. The results indicated that spermine can be employed as a polyamine target in tackling cancers; nonetheless, intensive experiments on cell lines, xenograft models and clinical trials are required before applying results to clinical atmosphere.…”

Smartphone-based paper strip assay for putrescine and spermidine detection using hybrid organic–inorganic perovskite with Eu3+ complex

“…Abnormal levels of these compounds in the human body can contribute to neurological problems, proliferation limitations, and cell transformation. [1][2][3][4] Therefore, their detection in physiological samples is crucial for diagnosing tumors and evaluating the efficacy of cancer therapy. 5 Currently, PUT/SPD are mainly detected using traditional techniques such as high-performance liquid chromatography/mass spectrometry, matrix-assisted laser desorption/ionization coupling with time-of-flight mass spectrometry, [6][7][8] electrophoresis, 9,10 and electrochemical methods, 11,12 However, these methods can be complex and require skilled personnel.…”