ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2010
Rottlerin stimulates apoptosis in pancreatic cancer cells through interactions with proteins of the Bcl-2 family.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- BCL2 inhibition in acute and chronic pancreatitis - is there a therapeutic perspective?Cell death discovery · 2026Review
- Natural Modulators of Aquaporins in Cancer Therapy: Functional Mechanisms and Clinical Potential.Molecules (Basel, Switzerland) · 2026Review
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- Targeted mitochondrial therapy for pancreatic cancer.Translational oncology · 2025Review
- Unraveling the Aquaporin-3 Inhibitory Effect of Rottlerin by Experimental and Computational Approaches.International journal of molecular sciences · 2023Article
- B7-H4 expression is upregulated by PKCδ activation and contributes to PKCδ-induced cell motility in colorectal cancer.Cancer cell international · 2022Article
- Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy.International journal of molecular sciences · 2021Review
- Improved synergistic anticancer efficacy of quercetin in combination with PI-103, rottlerin, and G0 6983 against MCF-7 and RAW 264.7 cells.In vitro cellular & developmental biology. Animal · 2019Article
- Rottlerin promotes autophagy and apoptosis in gastric cancer cell lines.Molecular medicine reports · 2018Article
- Tumor suppressive role of rottlerin in cancer therapy.American journal of translational research · 2018Review
- Rottlerin inhibits cell growth and invasion via down-regulation of EZH2 in prostate cancer.Cell cycle (Georgetown, Tex.) · 2018Article
- Article
- Rottlerin inhibits cell growth and invasion via down-regulation of Cdc20 in glioma cells.Oncotarget · 2016Article
- Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells.Oncotarget · 2016Article
- The Unfolded Protein Response Plays a Predominant Homeostatic Role in Response to Mitochondrial Stress in Pancreatic Stellate Cells.PloS one · 2016Article
- Rottlerin exhibits anti-cancer effect through inactivation of S phase kinase-associated protein 2 in pancreatic cancer cells.American journal of cancer research · 2016Article
- Targeting protein kinase C subtypes in pancreatic cancer.Expert review of anticancer therapy · 2015Review
- Antiproliferative Effect of Rottlerin on Sk-Mel-28 Melanoma Cells.Evidence-based complementary and alternative medicine : eCAM · 2015Article
- Rottlerin induces Wnt co-receptor LRP6 degradation and suppresses both Wnt/β-catenin and mTORC1 signaling in prostate and breast cancer cells.Cellular signalling · 2014Article
- Determination of Rottlerin, a Natural Protein Kinases C Inhibitor, in Pancreatic Cancer Cells and Mouse Xenografts by RP-HPLC Method.Journal of chromatography & separation techniques · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors.
Funding
Abstract
Rottlerin is a polyphenolic compound derived from Mallotus philipinensis. In the present study, we show that rottlerin decreased tumor size and stimulated apoptosis in an orthotopic model of pancreatic cancer with no effect on normal tissues in vivo. Rottlerin also induced apoptosis in pancreatic cancer (PaCa) cell lines by interacting with mitochondria and stimulating cytochrome c release. Immunoprecipitation results indicated that rottlerin disrupts complexes of prosurvival Bcl-xL with Bim and Puma. Furthermore, siRNA knockdown showed that Bim and Puma are necessary for rottlerin to stimulate apoptosis. We also showed that rottlerin and Bcl-2 and Bcl-xL inhibitor BH3I-2' stimulate apoptosis through a common mechanism. They both directly interact with mitochondria, causing increased cytochrome c release and mitochondrial depolarization, and both decrease sequestration of BH3-only proteins by Bcl-xL. However, the effects of rottlerin and BH3I-2' on the complex formation between Bcl-xL and BH3-only proteins are different. BH3I-2' disrupts complexes of Bcl-xL with Bad but not with Bim or Puma, whereas rottlerin had no effect on the Bcl-xL interaction with Bad. Also BH3I-2', but not rottlerin, required Bad to stimulate apoptosis. In conclusion, our results demonstrate that rottlerin has a potent proapoptotic and antitumor activity in pancreatic cancer, which is mediated by disrupting the interaction between prosurvival Bcl-2 proteins and proapoptotic BH3-only proteins. Thus rottlerin represents a promising novel agent for pancreatic cancer treatment.
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