Withaferin A activates TRIM16 for its anti"cancer activity in melanoma

Zsuzsanna Nagy; Belamy B. Cheung; Wing Tsang; Owen Tan; Mika Herath; Olivia C. Ciampa; Shadma Fatima; Daniel R. Carter; Glenn M. Marshall

doi:10.1038/s41598-020-76722-x

Withaferin A activates TRIM16 for its anti"cancer activity in melanoma

Zsuzsanna Nagy, Belamy B. Cheung, Wing Tsang, Owen Tan, Mika Herath, Olivia C. Ciampa, Shadma Fatima, Daniel R. Carter, Glenn M. Marshall

Western Sydney University

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

Abstract

Although selective BRAF inhibitors and novel immunotherapies have improved short-term treatment responses in metastatic melanoma patients, acquired resistance to these therapeutics still represent a major challenge in clinical practice. In this study, we evaluated the efficacy of Withaferin A (WFA), derived from the medicinal plant Withania Somnifera, as a novel therapeutic agent for the treatment of melanoma. WFA showed selective toxicity to melanoma cells compared to non-malignant cells. WFA induced apoptosis, significantly reduced cell proliferation and inhibited migration of melanoma cells. We identified that repression of the tumour suppressor TRIM16 diminished WFA cytotoxicity, suggesting that TRIM16 was in part responsible for the cytotoxic effects of WFA in melanoma cells. Together our data indicates that WFA has potent cytopathic effects on melanoma cells through TRIM16, suggesting a potential therapeutic application of WFA in the disease.

Original language	English
Article number	19724
Number of pages	9
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-76722-x
Publication status	Published - Dec 2020

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Publisher Copyright:
© 2020, The Author(s).

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Cite this

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title = "Withaferin A activates TRIM16 for its anti{"}cancer activity in melanoma",

abstract = "Although selective BRAF inhibitors and novel immunotherapies have improved short-term treatment responses in metastatic melanoma patients, acquired resistance to these therapeutics still represent a major challenge in clinical practice. In this study, we evaluated the efficacy of Withaferin A (WFA), derived from the medicinal plant Withania Somnifera, as a novel therapeutic agent for the treatment of melanoma. WFA showed selective toxicity to melanoma cells compared to non-malignant cells. WFA induced apoptosis, significantly reduced cell proliferation and inhibited migration of melanoma cells. We identified that repression of the tumour suppressor TRIM16 diminished WFA cytotoxicity, suggesting that TRIM16 was in part responsible for the cytotoxic effects of WFA in melanoma cells. Together our data indicates that WFA has potent cytopathic effects on melanoma cells through TRIM16, suggesting a potential therapeutic application of WFA in the disease.",

author = "Zsuzsanna Nagy and Cheung, {Belamy B.} and Wing Tsang and Owen Tan and Mika Herath and Ciampa, {Olivia C.} and Shadma Fatima and Carter, {Daniel R.} and Marshall, {Glenn M.}",

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AU - Nagy, Zsuzsanna

AU - Cheung, Belamy B.

AU - Tsang, Wing

AU - Tan, Owen

AU - Herath, Mika

AU - Ciampa, Olivia C.

AU - Fatima, Shadma

AU - Carter, Daniel R.

AU - Marshall, Glenn M.

PY - 2020/12

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N2 - Although selective BRAF inhibitors and novel immunotherapies have improved short-term treatment responses in metastatic melanoma patients, acquired resistance to these therapeutics still represent a major challenge in clinical practice. In this study, we evaluated the efficacy of Withaferin A (WFA), derived from the medicinal plant Withania Somnifera, as a novel therapeutic agent for the treatment of melanoma. WFA showed selective toxicity to melanoma cells compared to non-malignant cells. WFA induced apoptosis, significantly reduced cell proliferation and inhibited migration of melanoma cells. We identified that repression of the tumour suppressor TRIM16 diminished WFA cytotoxicity, suggesting that TRIM16 was in part responsible for the cytotoxic effects of WFA in melanoma cells. Together our data indicates that WFA has potent cytopathic effects on melanoma cells through TRIM16, suggesting a potential therapeutic application of WFA in the disease.

AB - Although selective BRAF inhibitors and novel immunotherapies have improved short-term treatment responses in metastatic melanoma patients, acquired resistance to these therapeutics still represent a major challenge in clinical practice. In this study, we evaluated the efficacy of Withaferin A (WFA), derived from the medicinal plant Withania Somnifera, as a novel therapeutic agent for the treatment of melanoma. WFA showed selective toxicity to melanoma cells compared to non-malignant cells. WFA induced apoptosis, significantly reduced cell proliferation and inhibited migration of melanoma cells. We identified that repression of the tumour suppressor TRIM16 diminished WFA cytotoxicity, suggesting that TRIM16 was in part responsible for the cytotoxic effects of WFA in melanoma cells. Together our data indicates that WFA has potent cytopathic effects on melanoma cells through TRIM16, suggesting a potential therapeutic application of WFA in the disease.

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Withaferin A activates TRIM16 for its anti"cancer activity in melanoma

Abstract

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Withaferin A activates TRIM16 for its anti"cancer activity in melanoma

Abstract

Bibliographical note

Open Access - Access Right Statement

UN SDGs

Access to Document

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Fingerprint

Cite this

Withaferin A activates TRIM16 for its anti"cancer activity in melanoma