Plant Compound Triggers Cell Death Pathway in Human Skin Cancer Cells

Jim Crocker
27th June, 2024

Plant Compound Triggers Cell Death Pathway in Human Skin Cancer Cells

An extract from watercress (Nasturtium officinale, pictured), rich in phenethyl isothiocyanate (PEITC), selectively kills malignant melanoma cells by inducing apoptosis through the activation of the intrinsic mitochondrial pathway and formation of the apoptosome.

Photo adapted from: Jo Roberts / CC BY (Source)

Key Findings

  • Researchers from The Cyprus Institute of Neurology & Genetics found that watercress extract, rich in PEITC, can selectively kill melanoma cells
  • The extract showed significant, time- and dose-dependent toxic effects on melanoma cells, while sparing non-melanoma and normal cells
  • The study confirmed that watercress extract induces cancer cell death through the intrinsic apoptosis pathway, involving key mitochondrial signals
Malignant melanoma is the most aggressive form of skin cancer, characterized by high rates of mortality and increasing incidence worldwide. Traditional treatments often provide limited long-term benefits due to acquired drug resistance, emphasizing the need for new therapeutic strategies[2]. Recent research from The Cyprus Institute of Neurology & Genetics has explored the potential of watercress extract, rich in phenethyl isothiocyanate (PEITC), as an anti-cancer agent against malignant melanoma[1]. The study evaluated the effects of watercress extract on various human cell lines, including melanoma (A375, COLO-679, COLO-800), non-melanoma epidermoid carcinoma (A431), and non-tumorigenic keratinocyte (HaCaT) cells. The chemical composition of the extract was characterized using advanced analytical techniques like UPLC MS/MS, revealing a high concentration of isothiocyanates, particularly PEITC. This compound has been previously noted for its anticancer properties[3]. To assess the cytotoxicity of the extract, researchers used the alamar blue assay, a test that measures cell viability based on metabolic activity. The results showed significant, time- and dose-dependent cytotoxic effects on all melanoma cell lines, while non-melanoma and non-tumorigenic cells displayed notable resistance. This selective cytotoxicity is crucial as it suggests that PEITC targets cancer cells more effectively than normal cells. Apoptosis, or programmed cell death, is a vital mechanism in cancer treatment as it leads to the elimination of malignant cells. The study employed a multiplex activity assay kit to measure the activation of caspases -3, -8, and -9, which are key enzymes in the apoptotic process. Additionally, quantitative real-time PCR (qRT-PCR) was used to identify major genes involved in apoptosis. The findings indicated that the watercress extract induced apoptosis through the intrinsic pathway, which is regulated by mitochondrial signals. Protein expression levels were further analyzed by western immunoblotting, confirming the involvement of several proteins in the apoptotic cascade. This comprehensive approach provided robust evidence that watercress extract, and specifically PEITC, can effectively trigger apoptosis in melanoma cells. These findings align with previous research on isothiocyanates (ITCs), which have shown a biphasic effect on cell growth and migration. At low concentrations, ITCs like sulforaphane (SFN) can promote cell proliferation and migration, while at higher concentrations, they inhibit these processes[3]. The current study supports the notion that the dose of ITCs is critical in determining their effect on cancer cells. Additionally, the study's results are consistent with earlier findings on the role of epigenetic alterations in melanoma progression and drug resistance[2]. By targeting the epigenome, compounds like PEITC could potentially overcome resistance to conventional therapies, offering a new avenue for treatment. The research also touches on the broader context of cancer and inflammation. Toll-like receptor 4 (TLR4) signaling has been implicated in cancer progression and inflammatory responses. Various phytochemicals, including those found in watercress, can inhibit TLR4 activation, thereby reducing inflammation and potentially hindering cancer progression[4]. This adds another layer of understanding to the anticancer properties of watercress extract. In summary, the study from The Cyprus Institute of Neurology & Genetics provides compelling evidence that watercress extract, rich in PEITC, can selectively induce apoptosis in melanoma cells through the intrinsic pathway. This research not only highlights the potential of PEITC as a promising anticancer agent but also underscores the importance of dose and context in the therapeutic application of phytochemicals.

MedicineHealthBiochem

References

Main Study

1) Naturally-derived phenethyl isothiocyanate modulates apoptotic induction through regulation of the intrinsic cascade and resulting apoptosome formation in human malignant melanoma cells.

Published 25th June, 2024

https://doi.org/10.1080/15376516.2024.2369666

Related Studies

2) Targeting the epigenome in malignant melanoma: Facts, challenges and therapeutic promises.

https://doi.org/10.1016/j.pharmthera.2022.108301

3) Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention.

https://doi.org/10.1371/journal.pone.0114764

4) The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive Phytochemicals Targeting the TLR4 Signaling Pathway.

https://doi.org/10.3390/ijms19092729


Related Articles

An unhandled error has occurred. Reload 🗙