Multifaceted antineoplastic curative potency of novel water-soluble methylimidazole-based oxidovanadium (IV) complex
Noyel Ghosh1, Samhita De1, Nikhil Ranjan Pramanik2
1Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, India.
Abstract:
A bunch of complexes harboring vanadium as metal centers have been reported to exhibit a wide array of antineoplastic properties that come under non‑platinum metallodrug series and emerge to offer alternative therapeutic strategies from the mechanistic behaviors of platinum-drugs. Though antineoplastic activities of vanado-complexes have been documented against several animal and xenografted human cancers, the definite mechanism of action is yet to unveil. In present study, a novel water soluble 1-methylimidazole substituted mononuclear dipicolinic acid based oxidovanadium (IV) complex (OVMI) has been evaluated for its antineoplastic properties in breast carcinoma both in vitro and in vivo. OVMI has been reported to generate cytotoxicity in human triple negative breast carcinoma cells, MDA-MB-231 as well as in mouse 4T1 cells by priming them for apoptosis. ROS-mediated, mitochondria-dependent as well as ER-stress-evoked apoptotic death seemed to be main operational hub guiding the cytotoxicity of OVMI in vitro. Moreover, OVMI has been noticed to elicit antimetastatic effect in vitro. Therapeutic application of OVMI has been extended on 4T1-based mammary tumor of female Balb/c mice, where it has been found to reduce tumor size, volume and restore general tissue architecture successfully to a great extent. Apart from that, OVMI has been documented to limit 4T1-based secondary pulmonary metastasis along with being non-toxic and biocompatible in vivo.
Insights
A novel oxidovanadium (IV) complex, OVMI, shows potent anticancer effects against breast cancer cells by inducing apoptosis. This metallodrug also reduced tumor growth and metastasis in vivo, demonstrating therapeutic potential.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Cancer Biology
Background:
- Vanadium complexes offer non-platinum metallodrug alternatives for cancer therapy.
- The precise mechanisms underlying vanado-complex antineoplastic activity require further elucidation.
Purpose of the Study:
- To evaluate the antineoplastic properties of a novel oxidovanadium (IV) complex (OVMI) in breast carcinoma.
- To investigate the in vitro and in vivo efficacy and mechanism of action of OVMI.
Main Methods:
- Synthesis and characterization of a water-soluble 1-methylimidazole substituted mononuclear dipicolinic acid based oxidovanadium (IV) complex (OVMI).
- In vitro cytotoxicity assays on human triple-negative breast carcinoma (MDA-MB-231) and mouse 4T1 cells.
- Investigation of apoptosis pathways (ROS-mediated, mitochondria-dependent, ER-stress-evoked) and antimetastatic effects in vitro.
- In vivo studies using a 4T1-based mammary tumor model in Balb/c mice to assess tumor reduction and metastasis inhibition.
Main Results:
- OVMI demonstrated significant cytotoxicity against MDA-MB-231 and 4T1 cells by inducing apoptosis.
- Apoptosis was mediated through ROS generation, mitochondrial dysfunction, and ER stress.
- OVMI exhibited antimetastatic effects in vitro and reduced primary tumor size and volume in vivo.
- OVMI successfully limited pulmonary metastasis and was found to be non-toxic and biocompatible in vivo.
Conclusions:
- OVMI is a promising novel oxidovanadium (IV) complex with significant in vitro and in vivo antineoplastic and antimetastatic activities against breast carcinoma.
- The cytotoxicity of OVMI is driven by multiple apoptotic pathways, highlighting its versatile mechanism of action.
- OVMI's biocompatibility and efficacy in reducing tumor burden and metastasis suggest its potential as a therapeutic agent for breast cancer.
More Related Videos
13:43Intraductal Delivery and X-ray Visualization of Ethanol-Based Ablative Solution for Prevention and Local Treatment of Breast Cancer in Mouse Models
Published on: April 1, 2022
12:57X-Ray Visualization of Intraductal Ethanol-Based Ablative Treatment for Prevention of Breast Cancer in Rat Models
Published on: December 9, 2022
