دورية أكاديمية
أعرض في EDS

Crotoxin induces cytotoxic effects in human malignant melanoma cells in both native and detoxified forms.

التفاصيل البيبلوغرافية
العنوان: Crotoxin induces cytotoxic effects in human malignant melanoma cells in both native and detoxified forms.
المؤلفون: Almeida TC; Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil., Giannotti KC; Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil., Ribeiro Silva LM; Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil., Marques-Porto R; Laboratory of Development and Innovation, Butantan Institute, Sao Paulo, Brazil., DeOcesano-Pereira C; Centre of Excellence in New Target Discovering (CENTD), Butantan Institute, Sao Paulo, Brazil., Camargo L; Centre of Excellence in New Target Discovering (CENTD), Butantan Institute, Sao Paulo, Brazil., Chudzinski-Tavassi AM; Centre of Excellence in New Target Discovering (CENTD), Butantan Institute, Sao Paulo, Brazil., Reid P; Celtic Biotech Ltd., Dublin, Ireland., Picolo G; Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil.
المصدر: Frontiers in pharmacology [Front Pharmacol] 2024 Jul 24; Vol. 15, pp. 1425446. Date of Electronic Publication: 2024 Jul 24 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Media] Country of Publication: Switzerland NLM ID: 101548923 Publication Model: eCollection Cited Medium: Print ISSN: 1663-9812 (Print) Linking ISSN: 16639812 NLM ISO Abbreviation: Front Pharmacol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Media]
مستخلص: Introduction: Melanoma, a highly aggressive skin cancer originating in melanocytes, poses a significant threat due to its metastatic potential. While progress has been made in treating melanoma with targeted therapies and immunotherapies, challenges persist. Crotoxin (CTX), the principal toxin in Crotalus durissus terrificus snake venom, exhibits various biological activities, including anti-tumoral effects across multiple cancers. However, its clinical use is limited by toxicity. Thus, exploring alternatives to mitigate adverse effects is crucial. Methods and Results: This study investigates the antitumoral potential of CTX in its native and in a detoxified form, in melanoma cells. Firstly, we demonstrated that detoxified CTX presented reduced phospholipase activity. Both forms proved to be more cytotoxic to SK-MEL-28 and MeWo melanoma cells than non-tumoral cells. In SK-MEL-28 cells, where cytotoxic effects were more pronounced, native and detoxified CTX induced increased necrosis and apoptosis rates. We also confirmed the apoptosis death demonstrated by the activation of caspase-3 and 7, and the formation of apoptotic bodies. Furthermore, both CTX caused cell cycle arrest at the G2/M phase, interfering with melanoma cell proliferation. Cell migration and invasion were also suppressed by both CTX. These results confirm the antitumoral potential of CTX. Discussion: The maintenance of the antiproliferative effects in the detoxified version, with reduced enzymatic activity often liked to harm effects, supports further studies to identify active parts of the molecule responsible for the interesting effects without causing substantial toxic events, contributing to the future use of CTX-derived drugs with safety and efficacy.
Competing Interests: Author PR was employed by Celtic Biotech Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Almeida, Giannotti, Ribeiro Silva, Marques-Porto, DeOcesano-Pereira, Camargo, Chudzinski-Tavassi, Reid and Picolo.)
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فهرسة مساهمة: Keywords: antitumoral activity; crotoxin; cytotoxicity; detoxified crotoxin; melanoma
تواريخ الأحداث: Date Created: 20240808 Latest Revision: 20240809
رمز التحديث: 20240809
مُعرف محوري في PubMed: PMC11303296
DOI: 10.3389/fphar.2024.1425446
PMID: 39114354
قاعدة البيانات: MEDLINE
الوصف
تدمد:1663-9812
DOI:10.3389/fphar.2024.1425446