Action of solamargine on TNFs and cisplatin-resistant human lung cancer cells
Related Experiment Video
Updated: Aug 22, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Chia-Hua Liang1, Li-Feng Liu, Li-Yen Shiu
1Department of Biochemistry, School of Medicine, Kaohsiung Medical University, Taiwan, ROC.
Abstract:
A loss of TNF receptors expression has been found in advanced lung cancers, and human A549 lung adenocarcinoma cells are resistant to the cytotoxic effects of TNF-alpha and cisplatin. Here, the mechanisms of the drug resistance of A549 were extensively studied by gene modulation of the cells by solamargine (SM) which was isolated from Solanum incanum herb. SM induced morphological changes of chromatin condensation, DNA fragmentation, and sub-G(1) peak in a DNA histogram of A549 cells, indicating cell death by apoptosis. SM elevated the expressions of TNF-R1 and -R2 and overcame the resistance of A549 cells to TNF-alpha and -beta. The recruitment of TRADD, FADD, and activation of caspase-8 and -3 in SM-treated A549 cells evidenced the activation of TNFRs signal transduction. In addition, release of cytochrome c from mitochondria, down-expression of Bcl-2 and Bcl-x(L), up-regulation of Bax, and caspase-9 activities were observed in SM-treated A549 cells. Combinational treatment of SM and cisplatin synergistically enhanced caspase-8, -9, and -3 activities in A549 cells. Thus, SM sensitizes A549 cells through TNFRs and mitochondria-mediated pathways and may have anticancer potential against TNFs- and cisplatin-resistance lung cancer cells.
Insights
Solamargine (SM) overcomes drug resistance in lung cancer cells by restoring TNF receptors and activating apoptosis pathways. This natural compound shows potential against resistant lung cancers when used alone or with cisplatin.
Area of Science:
- Molecular Biology
- Pharmacology
- Oncology
Background:
- Advanced lung cancers exhibit reduced TNF receptor expression, leading to resistance against TNF-alpha and cisplatin.
- Human A549 lung adenocarcinoma cells display resistance to TNF-alpha and cisplatin treatments.
Purpose of the Study:
- To investigate the mechanisms underlying drug resistance in A549 cells.
- To evaluate the potential of solamargine (SM) in overcoming this resistance.
Main Methods:
- Gene modulation of A549 cells using solamargine (SM) isolated from Solanum incanum.
- Analysis of apoptosis induction, TNF receptor expression, and signal transduction pathways.
- Assessment of mitochondrial-mediated apoptosis and caspase activation.
Main Results:
- SM induced apoptosis in A549 cells, evidenced by chromatin condensation and DNA fragmentation.
- SM upregulated TNF-R1 and TNF-R2 expression, sensitizing cells to TNF-alpha and TNF-beta.
- SM activated TNFRs signaling, caspase cascades (caspase-8, -3, -9), and mitochondrial pathways.
- Combination therapy with SM and cisplatin showed synergistic enhancement of caspase activities.
Conclusions:
- Solamargine sensitizes A549 lung adenocarcinoma cells via TNF receptor and mitochondria-mediated apoptosis.
- SM demonstrates potential as an anticancer agent against TNF and cisplatin-resistant lung cancers.
