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Updated: Dec 20, 2025
Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
Piperlongumine induces ROS mediated cell death and synergizes paclitaxel in human intestinal cancer cells
Laxminarayan Rawat1, Harsha Hegde2, Sugeerappa Laxmanappa Hoti2
1Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, K.K. Birla Goa Campus, NH-17B, Zuarinagar, Goa 403726, India.
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.
Insights
Piperlongumine (PL), a natural compound from long pepper, shows anti-cancer effects against intestinal cancer cells. It works by inducing oxidative stress and altering key cancer-related genes, suggesting potential for new intestinal cancer therapies.
Area of Science:
- Pharmacology
- Oncology
- Natural Products Chemistry
Background:
- Piperlongumine (PL), derived from Piper longum L, exhibits known anti-inflammatory and anti-cancer activities.
- Previous research has explored PL's efficacy in various cancers, but its impact on intestinal cancers remains uninvestigated.
Purpose of the Study:
- To evaluate the anti-neoplastic potential of Piperlongumine (PL) against human intestinal carcinoma cells in vitro.
- To elucidate the underlying mechanisms of action for PL's anti-cancer effects in intestinal cancer models.
Main Methods:
- Cytotoxicity assays were performed on INT-407 and HCT-116 human intestinal cancer cell lines.
- Intracellular reactive oxygen species (ROS) levels, mitochondrial function, and nuclear morphology were assessed.
- Gene expression analysis was conducted to determine the impact of PL on key regulatory proteins (P53, P21, BAX, BCL2, SMAD4, SURVIVIN).
- Synergistic effects of PL in combination with paclitaxel were investigated.
Main Results:
- Piperlongumine (PL) demonstrated significant inhibition of intestinal cancer cell proliferation in a dose- and time-dependent manner.
- PL treatment led to increased intracellular reactive oxygen species (ROS), suggesting induction of oxidative stress, mitochondrial dysfunction, and nuclear fragmentation.
- Upregulation of tumor suppressor genes (P53, P21, BAX, SMAD4) and downregulation of anti-apoptotic genes (BCL2, SURVIVIN) were observed.
- A synergistic anti-cancer effect was noted when PL was combined with paclitaxel.
Conclusions:
- Piperlongumine (PL) exhibits significant anti-neoplastic properties against human intestinal cancer cells in vitro.
- PL exerts its effects through mechanisms including oxidative stress induction and modulation of key cell death and survival pathways.
- PL holds promise as a potential therapeutic agent for intestinal cancers, possibly in combination with existing chemotherapies.
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