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Shengmai Formula suppressed over-activated Ras/MAPK pathway in C. elegans by opening mitochondrial permeability

Yan Liu1, Dejuan Zhi1, Menghui Li2

  • 1Gansu high throughput screening and creation center for health products, School of Pharmacy, Lanzhou University, Donggang West Road No. 199, Lanzhou 730020, P.R. China.

Scientific Reports
|December 17, 2016
PubMed

Insights

Shengmai formula (SM), a traditional Chinese medicine, unexpectedly acted as a pro-oxidant, triggering oxidative stress and apoptosis. This inhibited tumor-like growth in a Ras-related cancer model, suggesting SM as a potential anti-cancer drug.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Ras/MAPK pathway over-activation is implicated in ~30% of human cancers.
  • This pathway activation is linked to increased reactive oxygen species (ROS) accumulation.
  • Targeting ROS is a potential anti-cancer drug development strategy.

Purpose of the Study:

  • To investigate the effect of Shengmai formula (SM), a traditional Chinese medicine with antioxidant properties, on a cancer model.
  • To determine if SM can modulate the tumor-like phenotype associated with over-activated Ras/MAPK signaling.

Main Methods:

  • Utilized a C. elegans let-60 (gf) mutant model exhibiting a tumor-like multivulva phenotype.
  • Administered SM to assess its impact on the mutant's physiology and phenotype.
  • Analyzed mitochondrial permeability transition pore opening, oxidative stress, and key signaling pathways (p53, JNK, p38/MAPK).

Main Results:

  • SM treatment unexpectedly induced mitochondrial permeability transition pore opening via cyclophilin D regulation.
  • This led to increased oxidative stress and activation of p53, JNK, and p38/MAPK pathways.
  • SM triggered the mitochondrial apoptosis pathway and reduced the multivulva phenotype.

Conclusions:

  • Shengmai formula (SM) functions as a pro-oxidant agent, not an antioxidant, in this cancer model.
  • SM effectively inhibits tumor-like growth by inducing apoptosis.
  • SM shows potential as a therapeutic candidate for Ras-related cancers.

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