Artesunate induces G2/M cell cycle arrest through autophagy induction in breast cancer cells

Kai Chen1, Liu-Mei Shou, Fang Lin

  • 1aDepartment of Oncology, the First Affiliated Hospital of Soochow University bDepartment of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Pharmaceutical Science cJiangsu Institute of Clinical Immunology, Suzhou, China.

Anti-Cancer Drugs
|February 13, 2014
PubMed

Insights

Artesunate (ART) inhibits breast cancer cell growth by inducing autophagy, a type of cell death. ART also enhances chemotherapy effectiveness, suggesting its potential as a novel breast cancer treatment.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Breast cancer remains a significant global health challenge.
  • Novel therapeutic strategies are urgently needed to improve treatment outcomes.
  • Artesunate (ART), an antimalarial drug, shows potential anticancer properties.

Purpose of the Study:

  • To investigate the mechanism of action of artesunate (ART) in breast cancer cells.
  • To determine the role of autophagy in ART-induced anticancer effects.
  • To evaluate ART's potential to sensitize breast cancer cells to chemotherapy.

Main Methods:

  • Cell viability assays were performed on MCF-7 and MDA-MB-231 breast cancer cell lines.
  • Cell cycle analysis and Western blotting were used to assess cell cycle arrest and protein expression (p21, Beclin1, LC3).
  • Autophagy was modulated using 3-methyladenine (3-MA) and Beclin1 knockdown.
  • Synergistic effects of ART and epirubicin were evaluated.

Main Results:

  • Artesunate inhibited breast cancer cell proliferation and induced G2/M cell cycle arrest.
  • ART upregulated p21 expression and induced autophagy, evidenced by increased Beclin1 and LC3-II formation.
  • Inhibition of autophagy (using 3-MA or Beclin1 knockdown) reversed ART-induced effects.
  • ART sensitized breast cancer cells to epirubicin chemotherapy via an autophagy-dependent pathway.

Conclusions:

  • Artesunate exerts anticancer effects in breast cancer cells by inducing autophagy and cell cycle arrest.
  • Autophagy plays a crucial role in mediating the anti-breast cancer activity of ART.
  • ART enhances the efficacy of epirubicin chemotherapy, highlighting its potential as a novel therapeutic agent for breast cancer treatment.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.2K
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...
7.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.0K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
2.6K