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Piperlongumine induces ROS mediated cell death and synergizes paclitaxel in human intestinal cancer cells.

Abstract
Piperlongumine (PL), a herbal drug extracted from long pepper (Piper longum L), is known for its anti-inflammatory and anti-cancer properties. Although, its anti-cancer potential has been evaluated in cancer models like breast, pancreatic, gastric, hepatocellular and lung carcinoma, there is no report on its bio-activity evaluation in intestinal cancers. Here, we report the anti-neoplastic potential of PL against human intestinal carcinoma in-vitro and its possible mechanisms of action. Cytotoxicity studies demonstrate that PL inhibits cell proliferation of INT-407 and HCT-116 cells in a concentration and time-dependent manner. Also, PL elevated the levels of intracellular reactive oxygen species, which may lead to lethal oxidative stress, mitochondrial dysfunction, and nuclear fragmentation. Remarkably, P53, P21, BAX, and SMAD4 were significantly upregulated after PL treatment whereas; BCL2 and SURVIVIN were down-regulated. Moreover, the combination study also shows the synergistic effect of PL with the current chemotherapeutic drug paclitaxel. These findings suggest that PL possesses anti-neoplastic properties in intestinal cancer cells.
AuthorsLaxminarayan Rawat, Harsha Hegde, Sugeerappa Laxmanappa Hoti, Vijayashree Nayak
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 128 Pg. 110243 (Aug 2020) ISSN: 1950-6007 [Electronic] France
PMID32470748 (Publication Type: Journal Article)
CopyrightCopyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Dioxolanes
  • Reactive Oxygen Species
  • Doxorubicin
  • piperlonguminine
Topics
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Antineoplastic Combined Chemotherapy Protocols (pharmacology)
  • Cell Death (drug effects)
  • Cell Movement (drug effects)
  • Cell Proliferation (drug effects)
  • Colorectal Neoplasms (drug therapy, genetics, metabolism, pathology)
  • DNA Damage
  • Dioxolanes (pharmacology)
  • Dose-Response Relationship, Drug
  • Doxorubicin (pharmacology)
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Oxidative Stress (drug effects)
  • Reactive Oxygen Species (metabolism)
  • Time Factors

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