Tanshinone IIA induces autophagy in colon cancer cells through MEK/ERK/mTOR pathway
Jun Qian1, Yi Cao2, Junfeng Zhang3
1Department of Diagnostics of Chinese Medicine, School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Background:
Colon cancer is a common malignancy of the digestive tract. The search for effective drugs to treat colon cancer has become the focus of current researches. Tanshinone IIA (Tan IIA) is a fat-soluble component extracted from tanshinone, a traditional Chinese medicine. Tan IIA can modulate the occurrence and development of tumors, but its effect on autophagy in colon cancer cells has not been reported.
Methods:
Two types of colon cancer cell lines were selected and different concentrations of Tan IIA were used to treat cells at different time points. Cell Counting Kit-8 assay (CCK-8) was used to detect the effect of Tan IIA on cell proliferation; transmission electron microscopy was used to observe the formation of autophagosomes; reverse transcription-polymerase chain reaction (RT-qPCR) and western blot were used to detect the expression of autophagy related genes and proteins. Cell transfection was used to interfere with MEK (mitogen-activated extracellular signal-regulated kinase) expression, and RT-qPCR and western blot were used to detect the expression of MEK/ERK/mTOR pathway-related proteins.
Results:
Tan IIA resulted in a significant reduction in the viability of the two kinds of colon cancer cells. The number of autophagosomes increased significantly after the treatment of Tan IIA into these cells. Addition of autophagy inhibitor 3-MA (3-Methyladenine) improved the increase of autophagosomes in cells induced by Tan IIA. At the same time, Tan IIA induced the expression of autophagy-related proteins in the two colon cancer cell lines. When Tan IIA induced autophagy in colon cancer cells, the expression of MEK/ERK/mTOR pathway-related proteins increased significantly. After interfering with the expression of MEK, the expression of autophagy decreased significantly, indicating that Tan IIA promoted autophagy of colon cancer cells through MEK/ERK/mTOR pathway.
Conclusions:
Tan IIA stimulates autophagy in colon cancer cells through MEK/ERK/mTOR pathway, hence inhibiting the growth of colon cancer cells.
Insights
Tanshinone IIA (Tan IIA) stimulates autophagy in colon cancer cells by activating the MEK/ERK/mTOR pathway. This process inhibits colon cancer cell growth, offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Colon cancer remains a significant global health challenge, driving research for novel therapeutic agents.
- Tanshinone IIA (Tan IIA), a component of traditional Chinese medicine, shows potential in modulating tumor development.
- The impact of Tan IIA on autophagy in colon cancer cells was previously unreported.
Purpose of the Study:
- To investigate the effect of Tanshinone IIA (Tan IIA) on autophagy in colon cancer cells.
- To elucidate the molecular pathway, specifically the MEK/ERK/mTOR pathway, involved in Tan IIA-induced autophagy.
- To assess the therapeutic potential of Tan IIA in colon cancer treatment.
Main Methods:
- Utilized two colon cancer cell lines treated with varying concentrations and time points of Tan IIA.
- Assessed cell viability using Cell Counting Kit-8 (CCK-8) assay.
- Examined autophagosome formation via transmission electron microscopy and autophagy-related gene/protein expression using RT-qPCR and western blot.
- Investigated the role of the MEK/ERK/mTOR pathway by interfering with MEK expression.
Main Results:
- Tan IIA significantly reduced colon cancer cell viability.
- Tan IIA treatment led to a marked increase in autophagosome formation and autophagy-related protein expression.
- The MEK/ERK/mTOR pathway proteins showed increased expression upon Tan IIA treatment.
- Interference with MEK expression attenuated Tan IIA-induced autophagy, confirming pathway involvement.
Conclusions:
- Tanshinone IIA (Tan IIA) effectively stimulates autophagy in colon cancer cells.
- The MEK/ERK/mTOR pathway is crucial for Tan IIA-mediated autophagy induction.
- Tan IIA exhibits potential as an anti-cancer agent by inhibiting colon cancer cell growth via autophagy stimulation.
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