Nitro-Substituted Benzylic Organochalcogenides as Anticancer Agents: Unravelling the Multifaceted Pathways to Combat...

Area of Science:

• Medicinal Chemistry
• Cancer Biology
• Pharmacology

Background:

• Organochalcogens show promise as chemotherapeutics.
• Simultaneous targeting of multiple cancer pathways is largely unexplored.

Purpose of the Study:

• To investigate a novel 4-nitro-substituted benzylic diselenide (compound 7) as a multi-targeting anticancer agent.
• To elucidate the mechanisms of action against triple-negative breast cancer (TNBC).

Main Methods:

• Synthesis and characterization of diselenide 7.
• In vitro studies using MDA-MB-231 cells to assess pathway inhibition (Akt/mTOR, ERK, NF-κB) and cellular effects (ROS, DNA damage, mitochondrial dysfunction).
• In vivo studies in mice bearing breast adenocarcinoma to evaluate anti-tumor efficacy, angiogenesis, and metastasis markers (VEGF, MMP-9).

Main Results:

• Diselenide 7 demonstrated concerted inhibition of Akt/mTOR and ERK pathways, suppressing NF-κB-mediated inflammation and invasiveness in TNBC cells.
• Mechanistic studies revealed compound 7 induces reactive oxygen species (ROS), leading to DNA damage and mitochondrial dysfunction, ultimately causing cell death.
• In vivo, compound 7 significantly reduced tumor volume, downregulated VEGF and MMP-9, and extended lifespan in mice.

Conclusions:

• Diselenide 7 acts as a multi-targeting agent against aggressive breast cancer by disrupting key oncogenic signaling pathways and inducing cellular damage.
• The compound exhibits potent anti-tumor, anti-angiogenic, and anti-metastatic effects.
• This study highlights the therapeutic potential of small-molecule organoselenium compounds for cancer treatment.