{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T07:45:40Z","timestamp":1785743140800,"version":"3.56.0"},"reference-count":38,"publisher":"Scientific Scholar","content-domain":{"domain":["ijmr.org.in"],"crossmark-restriction":true},"short-container-title":["Indian J Med Res"],"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      Drug resistance and off-target toxicity remain major challenges in cancer therapy. Due to rapid proliferating nature of malignant cells, microtubule-targeting agents (MTAs) are widely used for chemotherapy, although their clinical efficacy is often limited by drug resistance and adverse effects. Objective of this study was to identify a novel therapeutic agent capable of selectively targeting microtubules in cancer cells while minimising toxicity to normal cells. Present study evaluates the chemotherapeutic potential of\n                      <jats:italic>Vibrio cholerae<\/jats:italic>\n                      haemagglutinin protease (HAP) as a novel MTA for gastric and colon cancers by investigating its role in microtubule degradation and apoptosis induction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Effects of HAP were evaluated in human gastric and colon cancer cells using cellular and molecular assays. Time-dependent live-cell imaging was employed to assess HAP internalisation and co-localisation within intracellular organelles. Explant cultures derived from human tumour tissues were used to replicate the tumour microenvironment and validate therapeutic responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HAP treatment activated protease-activated receptor 1 (PAR1), which is overexpressed in malignant cells, leading to an increase in intracellular reactive oxygen species (ROS) and facilitated HAP internalisation. Once internalised, HAP induced microtubule degradation through four mechanisms: ROS-mediated degradation of MAP2 and tau, destabilising microtubule network; enhancing tubulin-PARKIN interaction, enabling microtubule ubiquitination; and activation of lysosomal and proteasomal pathways to degrade microtubules. Collectively these events triggered apoptotic cascades in cancer cells and explant tissues, while normal healthy cells remained unaffected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation and conclusions<\/jats:title>\n                    <jats:p>HAP demonstrates strong potential as a selective anticancer therapeutic by inducing microtubule degradation and apoptosis without compromising viability of normal cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.25259\/ijmr_189_2026","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T07:01:12Z","timestamp":1785740472000},"page":"169-178","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microtubule disruption and apoptotic induction by\n                    <i>Vibrio cholerae<\/i>\n                    haemagglutinin protease: Implications for anticancer therapy in colon and gastric tumours"],"prefix":"10.25259","volume":"164","author":[{"given":"Tanusree","family":"Ray","sequence":"first","affiliation":[{"name":"Division of Molecular Pathophysiology, ICMR-National Institute for Research in Bacterial Infection, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinaki","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Medical Gastroenterology, Medical College and Hospital, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niraj","family":"Nag","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathophysiology, ICMR-National Institute for Research in Bacterial Infection, Kolkata, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Animesh","family":"Gope","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine, ICMR-National Institute for Research in 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