Santamarine Synergizes With Cisplatin via ROS/JNK Axis to Selectively Induce Apoptosis and DNA Damage in Oral Cancer...

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Santamarine (SAMA), a sesquiterpene lactone from Michelia compressa, has shown anticancer properties.
• The synergistic effects and mechanisms of SAMA combined with cisplatin in oral cancer remain underexplored.

Purpose of the Study:

• To investigate the combined effects of SAMA and cisplatin on oral cancer cells.
• To elucidate the underlying reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signaling pathways involved.

Main Methods:

• Cell viability (ATP assay), colony formation, and cell migration assays were performed on oral cancer cell lines (Ca9-22, CAL 27).
• Flow cytometry was used to assess cell cycle distribution, apoptosis (annexin V), and ROS levels.
• Western blotting and specific inhibitors (JNK inhibitor, NAC ROS scavenger) were employed to determine signaling pathways.

Main Results:

• SAMA and cisplatin exhibited synergistic antiproliferative effects, significantly reducing oral cancer cell viability and suppressing colony formation and migration.
• The combination induced cell cycle arrest (subG1, G2/M), elevated cellular and mitochondrial ROS, and promoted apoptosis via caspase activation.
• Significant DNA damage (γH2AX, 8-OHdG) was observed, while normal oral cells showed minimal toxicity, indicating selectivity.
• JNK pathway inhibition and ROS scavenging (NAC) attenuated the observed effects, confirming ROS-dependent JNK signaling.

Conclusions:

• SAMA synergizes with cisplatin to enhance oxidative stress, apoptosis, and DNA damage in oral cancer cells.
• The mechanism involves ROS-dependent activation of JNK signaling, leading to selective cytotoxicity.
• SAMA demonstrates potential as an adjunct therapy to cisplatin for oral cancer treatment.