Cucurbitacin E inhibits esophageal carcinoma cell proliferation, migration, and invasion by suppressing Rac1

Luquan Zhang1, Hao Liang, Yanzhong Xin

  • 1Esophageal Mediastinal Division of Thoracic Surgery, Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Anti-Cancer Drugs
|June 23, 2020
PubMed

Insights

Cucurbitacin E inhibits esophageal carcinoma cell growth by reducing Rac1 expression, thereby blocking the PI3K/AKT/mTOR pathway. This study reveals a novel mechanism for Cucurbitacin E

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Esophageal carcinoma is a significant global health concern.
  • Cucurbitacin E (CuE) shows potential antitumor activity, but its mechanism in esophageal cancer is unclear.
  • Rac1's role in esophageal carcinoma progression needs further elucidation.

Purpose of the Study:

  • To investigate the effects of Cucurbitacin E (CuE) on human esophageal carcinoma cells.
  • To elucidate the underlying mechanism of CuE's anticarcinoma activity, focusing on Rac1 and the PI3K/AKT/mTOR pathway.

Main Methods:

  • Human esophageal carcinoma cell lines (ECA109, EC9706) and normal cells (Het-1A) were used.
  • Rac1 expression was manipulated via sh-Rac1 and pCDNA3.1-Rac1 transfection.
  • Cell proliferation, migration, and invasion were assessed using MTT, EDU, scratch, and Transwell assays.
  • Western blotting analyzed the phosphorylation of AKT and mTOR.

Main Results:

  • Rac1 was highly expressed in esophageal carcinoma cells and promoted their proliferation, migration, and invasion.
  • CuE treatment decreased Rac1 expression, suppressed cell viability, and reduced AKT/mTOR phosphorylation.
  • Overexpression of Rac1 counteracted CuE's inhibitory effects.

Conclusions:

  • Cucurbitacin E inhibits esophageal carcinoma cell proliferation, invasion, and migration.
  • CuE exerts its effects by downregulating Rac1, consequently blocking the phosphoinositide 3-kinase/AKT/mTOR pathway.
  • Rac1 is a key mediator of CuE's anticarcinoma activity in esophageal cancer.

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...
5.4K
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...
4.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.6K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K