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Updated: May 15, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Alternative Pathways of Cancer Cell Death by Rottlerin: Apoptosis versus Autophagy
Claudia Torricelli1, Sara Salvadori, Giuseppe Valacchi
1Department of Physiology, University of Siena, Via Aldo Moro, 7-53100 Siena, Italy.
Abstract:
Since the ability of cancer cells to evade apoptosis often limits the efficacy of radiotherapy and chemotherapy, autophagy is emerging as an alternative target to promote cell death. Therefore, we wondered whether Rottlerin, a natural polyphenolic compound with antiproliferative effects in several cell types, can induce cell death in MCF-7 breast cancer cells. The MCF-7 cell line is a good model of chemo/radio resistance, being both apoptosis and autophagy resistant, due to deletion of caspase 3 gene, high expression of the antiapoptotic protein Bcl-2, and low expression of the autophagic Beclin-1 protein. The contribution of autophagy and apoptosis to the cytotoxic effects of Rottlerin was examined by light, fluorescence, and electron microscopic examination and by western blotting analysis of apoptotic and autophagic markers. By comparing caspases-3-deficient (MCF-7(3def)) and caspases-3-transfected MCF-7 cells (MCF-7(3trans)), we found that Rottlerin induced a noncanonical, Bcl-2-, Beclin 1-, Akt-, and ERK-independent autophagic death in the former- and the caspases-mediated apoptosis in the latter, in not starved conditions and in the absence of any other treatment. These findings suggest that Rottlerin could be cytotoxic for different cancer cell types, both apoptosis competent and apoptosis resistant.
Insights
Rottlerin induces cancer cell death through autophagy in apoptosis-resistant breast cancer cells. This natural compound offers a potential therapeutic strategy for various cancer types, including those resistant to conventional treatments.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Cancer cells evade apoptosis, limiting radiotherapy and chemotherapy efficacy.
- Autophagy is an emerging target for promoting cancer cell death.
- MCF-7 breast cancer cells are resistant to apoptosis and autophagy.
Purpose of the Study:
- To investigate Rottlerin's ability to induce cell death in MCF-7 breast cancer cells.
- To determine the role of autophagy and apoptosis in Rottlerin-induced cytotoxicity.
- To explore Rottlerin as a potential therapeutic agent for apoptosis-resistant cancers.
Main Methods:
- Utilized MCF-7 breast cancer cell lines (caspase-3 deficient and transfected).
- Employed light, fluorescence, and electron microscopy.
- Conducted western blotting for apoptotic and autophagic markers.
Main Results:
- Rottlerin induced noncanonical, Bcl-2-, Beclin 1-, Akt-, and ERK-independent autophagic death in caspase-3 deficient MCF-7 cells.
- Rottlerin induced caspase-mediated apoptosis in caspase-3 transfected MCF-7 cells.
- Cytotoxicity was observed in non-starved conditions without additional treatments.
Conclusions:
- Rottlerin can induce distinct cell death pathways (autophagic or apoptotic) depending on cellular context.
- Rottlerin demonstrates potential as a cytotoxic agent for both apoptosis-competent and apoptosis-resistant cancer cells.
- This study highlights Rottlerin as a promising natural compound for cancer therapy.
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