Salidroside reduces renal cell carcinoma proliferation by inhibiting JAK2/STAT3 signaling

Cai Lv1, Yuan Huang2, Zhen-Xiang Liu1

  • 1Department of Urology, Haikou Municipal Hospital, Haikou, Hainan, China.

Insights

Salidroside demonstrates significant anticancer effects against renal cell carcinoma by inhibiting cell growth and inducing apoptosis. This natural compound shows promise as a therapeutic strategy by modulating the JAK2/STAT3 signaling pathway.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Renal cell carcinoma (RCC) is a significant global health concern with limited effective treatments.
  • Salidroside, a natural compound, has shown potential anticancer activities, necessitating further investigation in RCC.

Purpose of the Study:

  • To evaluate the efficacy of salidroside in inhibiting renal cell carcinoma (RCC) growth in vitro and in vivo.
  • To elucidate the underlying molecular mechanisms of salidroside's anticancer effects in RCC.

Main Methods:

  • Cell viability and proliferation assays (Cell Counting Kit-8, colony formation) were performed on RCC cell lines (A498, 786-0).
  • In vivo tumor growth was assessed using a mouse xenograft model.
  • Cell cycle, apoptosis, and protein expression (JAK2/STAT3 signaling) were analyzed via flow cytometry and western blotting.

Main Results:

  • Salidroside significantly reduced RCC cell viability and colony formation in a dose- and time-dependent manner.
  • In vivo studies showed that salidroside suppressed tumor growth in the mouse xenograft model.
  • Salidroside induced G1 phase cell cycle arrest and apoptosis, and decreased phosphorylated JAK2 and STAT3 levels.

Conclusions:

  • Salidroside exhibits potent anticancer properties against renal cell carcinoma.
  • The mechanism involves the modulation of the JAK2/STAT3 signaling pathway.
  • Salidroside represents a potential therapeutic candidate for renal cell carcinoma treatment.

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.7K
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...
5.0K
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...
6.1K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.6K
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...
6.2K
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...
5.4K