Latcripin-7A, derivative of Lentinula edodes C91-3, reduces migration and induces apoptosis, autophagy, and cell cycle arrest at G1 phase in breast cancer cells

Appl Microbiol Biotechnol. 2020 Dec;104(23):10165-10179. doi: 10.1007/s00253-020-10918-z. Epub 2020 Oct 12.

Abstract

Due to the high mortality rate and an increase in breast cancer incidence, it has been challenging for researchers to come across an effective chemotherapeutic strategy with minimum side effects. Therefore, the need for the development of effective chemotherapeutic drugs is still on the verge. Consequently, we approached a new mechanism to address this issue. The naturally available peptide named latcripin-7A (LP-7A), extracted from a mushroom called Lentinula edodes, provided us promising results in terms of growth arrest, apoptosis, and autophagy in breast cancer cells (MCF-7 and MDA-MB-231). Expressions of protein markers for apoptosis, autophagy, and cell cycle were confirmed via Western blot analysis. Migration and invasion assays were performed to analyze the anti-migratory and anti-invasive properties of LP-7A, while cell cycle analysis was performed via flow cytometry to evaluate its affect over cell growth. Supportive assays were performed like acridine orange, Hoechst 33258 stain, DNA fragmentation, and mitochondrial membrane potential (MMP) to further confirm the anticancer effect of LP-7A on breast cancer cell lines. It is concluded that LP-7A effectively reduces migration and promotes apoptosis as well as autophagy in MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell growth arrest at G0/G1 phase and decreasing mitochondrial membrane potential without adverse effects on MCF-10A normal breast cells. KEY POINTS: • In this study, we have investigated the anti-cancer activity of novel latcripin-7A (LP-7A), a protein extracted as a result of de novo characterization of Lentinula edodes C91-3. • We conclude in our research work that LP-7A can initiate diverse cell death-related events, i.e., apoptosis and autophagy in both triple-positive and triple-negative breast cancer cell lines by interacting with different nodes of cellular signaling that can further be investigated in vivo to gain a better understanding.

Keywords: Apoptosis; Autophagy; Breast cancer; Latcripin-7A; Lentinula edodes.

MeSH terms

  • Apoptosis
  • Autophagy
  • Breast Neoplasms* / drug therapy
  • Cell Cycle
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Peptides
  • Shiitake Mushrooms*

Substances

  • Peptides