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Updated: Jun 26, 2026
Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
Published on: August 21, 2019
Effect of Ganoderma on drug-sensitive and multidrug-resistant small-cell lung carcinoma cells
David Sadava1, David W Still, Ryan R Mudry
1Division of Tumor Cell Biology, Beckman Research Institute at City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA. dsadava@jsd.claremont.edu
Abstract:
Multidrug resistance is a major problem in small-cell lung cancer (SCLC). Ganoderma lucidum is a widely used herb in traditional Chinese medicine. We tested the effects of Ganoderma on drug-sensitive (H69) and multi-drug resistant (VPA) human SCLC cells. Both cells showed equal cytotoxicity when incubated with extracts of mycelia of 9 species of Ganoderma, including G. lucidum. Cells treated with the IC(50) of cytotoxic Ganoderma and analyzed by flow cytometry-PI staining showed increases in S phase. When compared untreated controls or SCLC cells treated with extracts of non-cytotoxic Ganoderma species, cells treated with extracts of cytotoxic Ganoderma species responded with an induction of apoptosis similar to cells treated with the chemotherapeutic drugs etoposide and doxorubicin. This was shown by four criteria: increased DNA fragmentation within cells as measured by ELISA; increased TUNEL staining for DNA breaks; increased specific activities of caspases 3 and 9, but not caspase 8 by colorimetric assays, indicating the endogenous pathway; and similar patterns changes in the expressions of 9 genes involved in the cell cycle/apoptosis, as measured by RT-PCR and capillary electrophoresis. Pre-incubation of drug-resistant SCLC cells with cytotoxic Ganoderma reduced the IC(50) for etoposide (3.4-0.21 microM) and doxorubicin (0.19-0.04 microM). These results show that extracts of several species of Ganoderma are cytotoxic to both drug-sensitive and drug-resistant SCLC cells, are pro-apoptotic, induce gene expression patterns that are similar to SCLC cells treated with chemotherapeutic drugs, and can reverse resistance to chemotherapeutic drugs.
Insights
Ganoderma extracts show cytotoxicity against small-cell lung cancer (SCLC) cells, inducing apoptosis and reversing drug resistance. This traditional Chinese medicine offers potential for SCLC treatment.
Area of Science:
- Oncology
- Pharmacology
- Traditional Chinese Medicine
Background:
- Multidrug resistance (MDR) is a significant challenge in treating small-cell lung cancer (SCLC).
- Ganoderma lucidum, a mushroom used in traditional Chinese medicine, has potential therapeutic properties.
Purpose of the Study:
- To investigate the cytotoxic and chemosensitizing effects of Ganoderma extracts on drug-sensitive and drug-resistant SCLC cell lines.
- To elucidate the mechanisms underlying Ganoderma's effects on SCLC cells, including apoptosis induction and gene expression modulation.
Main Methods:
- Cytotoxicity assays using drug-sensitive (H69) and drug-resistant (VPA) SCLC cells treated with Ganoderma extracts.
- Flow cytometry for cell cycle analysis, ELISA and TUNEL staining for apoptosis detection.
- Colorimetric assays for caspase activity, RT-PCR, and capillary electrophoresis for gene expression analysis.
- Chemotherapy drug sensitivity assays (etoposide, doxorubicin) after pre-incubation with Ganoderma.
Main Results:
- Ganoderma extracts exhibited cytotoxicity against both drug-sensitive and drug-resistant SCLC cells.
- Ganoderma treatment induced S-phase arrest and apoptosis, evidenced by DNA fragmentation, caspase activation (caspase 3 and 9), and altered gene expression.
- Pre-incubation with cytotoxic Ganoderma extracts significantly reduced the IC(50) values for etoposide and doxorubicin in drug-resistant SCLC cells, reversing chemoresistance.
Conclusions:
- Ganoderma species extracts possess cytotoxic and pro-apoptotic properties against SCLC cells.
- Ganoderma extracts can modulate SCLC cell cycle and apoptosis-related gene expression, mimicking chemotherapy drug effects.
- Ganoderma extracts demonstrate potential in overcoming multidrug resistance in SCLC, suggesting a role as an adjuvant therapy.
