Targeting the weak point of cancer by induction of necroptosis

Xun Hu1, Weidong Han, Ling Li

  • 1Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China. huxun@zju.edu.cn

Autophagy
|July 10, 2007
PubMed

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

Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
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 Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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 Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...