Exploring the Ca2+ signaling and cytotoxicity induced by the alantolactone in breast cancer cells and its potential implications in treatment using the Ca2+ chelating agent BAPTA-AM
Year: 2025
Type: article
Abstract: Alantolactone, a bioactive sesquiterpene lactone derived from the roots of Inula helenium (elecampane), has garnered attention in biomedical and pharmacological research for its diverse therapeutic properties, including anticancer, anti-inflammatory, antimicrobial, and antioxidant activities. Despite its well-documented bioactivity, the effects of alantolactone on calcium ion (Ca2+) signaling and the underlying mechanisms in human breast cancer cells remain poorly understood. This study explored how alantolactone influences intracellular Ca2+ levels ([Ca2+]i), cell viability, and the role of Ca2+-dependent pathways in T-47D human breast cancer cells. Specifically, it examined the relationship between Ca2+ signaling and cytotoxicity in cells exposed to alantolactone, with or without the Ca2+ chelator BAPTA-AM. The findings reveal that alantolactone (25–75 μM) increases [Ca2+]i in a concentration-dependent manner, while concentrations of 25–100 μM induce cytotoxicity, an effect that can be reversed by BAPTA-AM pre-treatment. Removing extracellular Ca2+ significantly inhibits Ca2+ influx, and both SKF96365 and 2-APB, modulators of store-operated Ca2+ channels, block the alantolactone-induced Ca2+ entry. Additionally, in a Ca2+-free environment, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump, suppresses the alantolactone-induced rise in [Ca2+]i, while alantolactone reduces the [Ca2+]i increase triggered by thapsigargin. Moreover, inhibiting phospholipase C (PLC) with U73122 abolishes the alantolactone-induced [Ca2+]i elevation. These results suggest that alantolactone-induced cell death in T-47D cells is Ca2+-dependent, involving Ca2+ entry via store-operated channels and Ca2+ release from the endoplasmic reticulum, with PLC playing a pivotal role. Importantly, the ability of BAPTA-AM to reverse alantolactone's cytotoxic effects highlights its potential therapeutic significance in breast cancer research.
Source: Toxicology Research
Authors: Chun-Lang Su, Po-Min Chang, Wei-Zhe Liang
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W4410248853