Nano-hydroxyapatite promotes cell apoptosis by co-activating endoplasmic reticulum stress and mitochondria damage to...

Area of Science:

• Biomaterials Science
• Cancer Biology
• Cellular and Molecular Mechanisms

Background:

• Nano-hydroxyapatite (n-HA) shows anti-tumor effects, but its precise mechanisms are not fully understood.
• Endoplasmic reticulum (ER) and mitochondria are crucial for calcium (Ca2+) homeostasis and cellular stress responses.
• The interplay between ER and mitochondria in Ca2+ regulation is vital for preventing cellular damage.

Purpose of the Study:

• To investigate the anti-tumor effectiveness of needle-like n-HA.
• To elucidate the underlying cellular and molecular mechanisms of n-HA's anti-glioma effects.
• To explore the role of ER-mitochondria interplay in n-HA-induced cancer cell apoptosis.

Main Methods:

• Fabrication of needle-like nano-hydroxyapatite (n-HA).
• In vitro studies on glioma cell growth and invasion.
• Analysis of ER stress biomarkers, intracellular reactive oxygen species, and mitochondrial membrane potential.
• In vivo experiments to assess tumor growth inhibition.

Main Results:

• n-HA significantly reduced glioma cell growth and invasion in vitro.
• n-HA treatment upregulated ER stress biomarkers (GRP78, p-IRE1, p-PERK, PERK, ATF6) and activated CHOP, inducing apoptosis.
• n-HA caused increased reactive oxygen species, mitochondrial membrane depolarization, and downstream apoptotic signaling, indicating Ca2+ overload and mitochondrial damage.
• In vivo studies confirmed n-HA's ability to induce ER stress and mitochondrial damage, effectively restraining glioma tumor growth.

Conclusions:

• n-HA induces cancer cell apoptosis by co-activating ER stress and mitochondrial damage.
• The findings offer new insights into ER-mitochondria targeted anti-tumor therapies.
• n-HA presents a promising therapeutic agent for glioma treatment.