ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Pharmacology of Anti-Cancer Drugs

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1544666

This article is part of the Research TopicUnlocking Autophagy’s Full Potential: Embracing a Multidimensional Approach for Targeted Cancer TreatmentView all 4 articles

Anticancer Activity of RM-3-22: A TAZQ-Based Hydroxamic Acid Derivative Targeting NSCLC In Vitro and In Vivo

Provisionally accepted
Essha ChatterjeeEssha Chatterjee1Ram SharmaRam Sharma2Biswajit DeyBiswajit Dey1Hoshiyar SinghHoshiyar Singh1Aliva NaikAliva Naik1Anjesh KhanAnjesh Khan1Ankush BansodeAnkush Bansode1Santanu BasakSantanu Basak1Ritika SachdevaRitika Sachdeva2Anamika SharmaAnamika Sharma1Rahul KumarRahul Kumar1Pankaj Kumar SinghPankaj Kumar Singh1Dr. Pradeep Kumar NaikDr. Pradeep Kumar Naik3Kunal NepaliKunal Nepali2Santosh Kumar GuruSantosh Kumar Guru1*
  • 1National Institute of Pharmaceutical Education and Research, Hyderabad, Andhra Pradesh, India
  • 2Taipei Medical University, Taipei, Taipei County, Taiwan
  • 3Department of Biotechnology and Bioinformatics, Sambalpur University, Sambalpur, India

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Lung cancer remains the leading cause of cancer-related deaths, necessitating novel therapeutic strategies. We developed RM-3-22, a TAZQ-based hydroxamic acid derivative and HDAC inhibitor, and evaluated its anticancer activity in A549 adenocarcinoma cells. RM-3-22 significantly reduced tumor growth and cell viability in 2D and 3D cultures. Mechanistically, it induced autophagy via inhibition of the PI3K/Akt/mTOR pathway, induced G2/M cell cycle arrest, and triggered caspase-dependent apoptosis. Additionally, RM-3-22 upregulated FTH1, a tumor suppressor, reinforcing its anticancer potential. Notably, RM-3-22 exhibited lower toxicity to normal cells, underscoring its selectivity. Our findings highlight RM-3-22 as a promising therapeutic candidate for NSCLC.

Keywords: Apoptosis, Autophagy, cell cycle arrest, Cell Death, PI3K/Akt/mTOR pathway

Received: 13 Dec 2024; Accepted: 21 Apr 2025.

Copyright: © 2025 Chatterjee, Sharma, Dey, Singh, Naik, Khan, Bansode, Basak, Sachdeva, Sharma, Kumar, Singh, Naik, Nepali and Guru. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Santosh Kumar Guru, National Institute of Pharmaceutical Education and Research, Hyderabad, Andhra Pradesh, India

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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