Related Experiment Video
Updated: Jul 13, 2026

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Targeting the weak point of cancer by induction of necroptosis
1Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China. huxun@zju.edu.cn
Abstract:
Targeting the "weak point" of cancers, especially the apoptotic/drug resistant cancers, is critical for the success of cancer chemotherapy. We found that the drug resistant cancer cell lines overexpressing P-gp, MRP1, BCRP, Bcl-2 and Bcl-xL are susceptible to shikonin, a necroptotic inducer, despite the fact that they are highly resistant to a variety of anticancer agents such as anthracycline antibiotics, vinca alkaloids, taxanes, epipodophylotoxins, etc. These findings reveal that, although apoptotic/drug resistance is a formidable "stronghold" of cancer against chemotherapy, necroptotic susceptibility is an intrinsic "weak point" of cancer. Therefore, targeting the weakness of cancer by induction of necroptosis may have significant potential in cancer chemotherapy, especially in the apoptotic/drug resistant cancers.
Insights
Shikonin effectively targets drug-resistant cancers by inducing necroptosis, a cell death pathway that bypasses common resistance mechanisms like P-gp overexpression. This offers a new strategy for treating resistant tumors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cancer chemotherapy faces challenges with drug-resistant tumors.
- Resistance often involves overexpression of proteins like P-gp, MRP1, BCRP, Bcl-2, and Bcl-xL, which inhibit apoptosis.
- Targeting these resistance mechanisms is crucial for effective cancer treatment.
Purpose of the Study:
- To investigate the efficacy of shikonin against drug-resistant cancer cell lines.
- To identify a novel therapeutic strategy by targeting cancer's "weak point" through necroptosis induction.
Main Methods:
- Utilized drug-resistant cancer cell lines overexpressing key resistance proteins.
- Administered shikonin, a known necroptotic inducer.
- Assessed cancer cell susceptibility to shikonin.
Main Results:
- Drug-resistant cancer cell lines were susceptible to shikonin.
- Shikonin induced necroptosis, bypassing common apoptotic resistance pathways.
- This susceptibility was observed despite resistance to conventional chemotherapeutic agents.
Conclusions:
- Necroptosis induction represents a viable therapeutic strategy for overcoming chemoresistance.
- Shikonin's ability to induce necroptosis highlights its potential in treating resistant cancers.
- Targeting cancer's intrinsic "weak point" of necroptosis susceptibility is a promising avenue for chemotherapy.
Related Concept Videos
Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
The Intrinsic Apoptotic Pathway
