Capsaicin Exerts Antitumor Activity in Mesothelioma Cells

Our plain-English summary of Capsaicin Exerts Antitumor Activity in Mesothelioma Cells, by E. Andretta, A. Costa, E. Ventura, et al (Nutrients, 2024).

The study

• Authors: E. Andretta, A. Costa, E. Ventura, M. Quintiliani, S. Damiano, A. Giordano, A. Morrione, R. Ciarcia
• Journal: Nutrients
• Published: 2024;16(21)
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background/objectives: Mesothelioma is an aggressive cancer with limited treatment options. Mesothelioma therapy often involves a multimodal approach including surgery, radiotherapy and chemotherapy. However, the prognosis for patients remains poor. Difficult diagnosis, late symptoms when the tumor is in an advanced stage and the onset of chemotherapy resistance make mesothelioma difficult to treat. For this reason, it is essential to discover new pharmacological approaches. Capsaicin (CAPS) is the active compound of chili peppers. Based on CAPS's anticancer properties on various tumor lines and its chemo-sensitizing action on resistant cells, in this study, we evaluated the effects of CAPS on mesothelioma cells to assess its potential use in mesothelioma therapy.

Methods: To evaluate antiproliferative effects of CAPS, we performed MTS assays on various mesothelioma cells, representative of all major mesothelioma subtypes. Transwell migration and wound-healing assays were used to examine the effect of CAPS on mesothelioma cell migration. We also determined the effects of CAPS on oncogenic signaling pathways by assessing the levels of AKT and MAPK activation.

Results: In this study, we show that CAPS significantly reduces proliferation of both parental and cisplatin-resistant mesothelioma cells. CAPS promotes S-phase cell cycle arrest and inhibits lateral motility and migration of mesothelioma cells. Accordingly, CAPS suppresses AKT and ERK1/2 activation in MSTO-211H and NCI-H2052 cells. Our results support an antitumor effect of CAPS on cisplatin-resistant mesothelioma cells, suggesting that it may reduce resistance to cisplatin.

Conclusions: Our results could pave the way for further studies to evaluate the use of CAPS for mesothelioma treatment.

In plain English

This was a laboratory study of cancer cells grown in dishes. It did not study patients or asbestos exposure. The authors treated four human mesothelioma cell lines, representing the epithelioid, sarcomatoid and biphasic subtypes, with capsaicin, the active compound of chili peppers. They also tested cisplatin-resistant versions of two of these lines, made in their laboratory. Capsaicin at 200 µM significantly reduced the growth of three lines and of both cisplatin-resistant lines. The fourth line (NCI-H28) needed 250 or 300 µM. Capsaicin significantly increased the share of cells held in the S phase of the cell cycle in three lines. It reduced cell migration in most of the tests and reduced invasion in the one line tested. It also significantly inhibited activation of the AKT and ERK1/2 signaling proteins in two lines. The authors concluded that these results support a possible use of capsaicin. They added that it must first be tested in 3D or animal models before its use as a clinical treatment can be evaluated.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on human mesothelioma cell lines
• Who was studied: Four commercially obtained human malignant mesothelioma cell lines: NCI-H2052 (sarcomatoid), NCI-H2452 and NCI-H28 (epithelioid), and MSTO-211H (biphasic). The study also used cisplatin-resistant MSTO-211H and NCI-H2052 cells, which the authors generated in their laboratory by long-term exposure to increasing cisplatin concentrations. No human subjects were studied.
• Exposure: Capsaicin dissolved in DMSO and added to the cell medium for 24, 48 and 72 hours, at 50 to 200 µM for most lines and up to 300 µM for NCI-H28 cells. Cells given DMSO alone served as controls. Asbestos exposure was not studied.
• Main results:
  • Capsaicin at 50 µM and 100 µM did not impair growth of any line compared with DMSO. At 200 µM it significantly reduced growth of MSTO-211H, NCI-H2052 and NCI-H2452 cells but not NCI-H28 cells. Growth of NCI-H28 cells was significantly reduced at 250 µM and 300 µM.
  • IC50 is the capsaicin concentration that halved cell growth. After 72 hours it was 189.5 µM for MSTO-211H, 173.0 µM for NCI-H2052, 191.6 µM for NCI-H2452 and 242.4 µM for NCI-H28. After 24 hours it was 193.6, 216.1, 231.4 and 325.2 µM respectively. Values were lower for the sarcomatoid and biphasic lines than for the epithelioid lines.
  • Capsaicin at 200 µM reduced growth of both cisplatin-resistant cell lines (MSTO-211H and NCI-H2052) compared with DMSO-treated cells. This was based on two independent experiments performed in triplicate.
  • After 48 hours at 200 µM, the share of cells in S phase rose significantly in two lines. In MSTO-211H cells it was 21.9% plus or minus 0.566, versus 9.8% plus or minus 3.39 with DMSO. In NCI-H2052 cells it was 22.1% plus or minus 3.68, versus 8.15% plus or minus 1.91 with DMSO. In NCI-H2452 cells the S-phase increase was not significant. In NCI-H28 cells a significant S-phase increase was seen only after 72 hours at 300 µM: 21.45% plus or minus 1.34, versus 10.57% plus or minus 1.93 with DMSO.
  • In wound-healing (scratch) tests, capsaicin reduced closure of the scratched area in two lines. For NCI-H2452 cells at 100 µM, closure was 45.90% versus 69.62% with DMSO after 72 hours. For NCI-H28 cells at 200 µM, closure was 32.34% versus 67.56% at 48 hours, and 44.44% versus 86.62% at 72 hours. Capsaicin at 100 µM did not affect lateral motility of NCI-H2052 cells.
  • Capsaicin reduced migration through Transwell membranes in three lines: NCI-H2052 and MSTO-211H cells at 100 µM, and NCI-H28 cells at 200 µM. These concentrations did not affect growth. At 100 µM it also reduced the invasion of NCI-H2052 cells through Matrigel-coated chambers.
  • Capsaicin significantly inhibited activation of AKT and ERK1/2 in MSTO-211H and NCI-H2052 cells. In NCI-H28 cells, capsaicin at 250 µM only delayed AKT and ERK1/2 activation.
• The authors' conclusion: The authors concluded that their in vitro results support the possible use of capsaicin, including against cisplatin-resistant cells. They stated that validation in 3D models or animal xenograft models is required before evaluating capsaicin in clinical therapy.
• Limitations the authors state:
  • The findings come from cell lines only. Further validation in 3D or animal models is needed before clinical evaluation.
  • The effects of low versus high capsaicin concentrations, and of different routes of administration, still need to be defined in mouse models of mesothelioma.
  • How capsaicin affects cell death (apoptosis) in mesothelioma cells is not yet clear. The authors described their caspase-3 finding as preliminary.
  • Capsaicin has low bioavailability and a short half-life, which bears on any clinical use.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Chemotherapy, Prognosis, Cisplatin.

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• CpG-oligodeoxynucleotides exert remarkable antitumor activity against diffuse malignant peritoneal mesothelioma orthotopic xenografts — M. De Cesare, L. Sfondrini, et al. (2016)
• Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines — L. Cortes-Dericks, L. Froment, et al. (2016)
• Modulation of Calretinin Expression in Human Mesothelioma Cells Reveals the Implication of the FAK and Wnt Signaling Pathways in Conferring Chemoresistance towards Cisplatin — J. Wörthmüller, V. Salicio, et al. (2019)
• Combined treatment with cisplatin and sirolimus to enhance cell death in human mesothelioma — M.L. Hartman, J.M. Esposito, et al. (2010)

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