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<p>Oral squamous cell carcinoma (OSCC) is a predominant form of cancer that affects the oral cavity of the mucosal epithelium layer. Withanolides are a structurally related family of natural products extracted from the herbal plant (Withania genus). Many active members of this family play a major role in the prevention and cure of OSCC, while some also show potent activity as anticancer agents. The data covered by this review were collected from different databases, including PubMed, Scopus, and Web of Science, focusing on studies relevant to withanolides and their applications against oral squamous cell carcinoma from 2020 to 2025. The core structure of withanolides consists of a steroidal ring system along with a lactone moiety. Presently, more than 1200 withanolides with different lactones and an array of different functional groups have been identified. This article focuses on several key derivatives, elucidating their targets and signalling molecular pathways that modulate cellular survival, proliferation, invasion, and metastasis. As an example, withaferin A (WA) is a well-studied withanolide that exhibits potent anticancer effects in oral squamous cell carcinoma. WA has been shown to modulate key signalling pathways such as NF-κB, PI3K/Akt, and heat shock protein regulation, leading to apoptosis, autophagy, and cell cycle arrest. The classification of this large family of withanolides is presented, based on structural differences correlated with their anticancer effects, molecular targets, and signalling pathways. Additionally, the potential of these derivatives in enhancing therapeutic strategies and overcoming resistance to conventional treatments is described and summarized. By understanding the intricate mechanisms through which withanolides exert their effects, future research can develop novel cancer therapies that leverage the efficacy of these natural compounds.</p>

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Withanolides as molecular inhibitors in oral squamous cell carcinoma: unveiling anticancer mechanisms and therapeutic targets

  • 期刊论文

  • 发表日期：

    2026年4月6日

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  • Vishnu Malakar,
  • Bharat Sankhla,
  • Chandi C. Malakar,
  • Ashish Runthala,
  • Pratap Chand Mali,
  • S. K. Sireesha,
  • Ronald E. Viola,
  • Nitesh Kumar Poddar

摘要

Oral squamous cell carcinoma (OSCC) is a predominant form of cancer that affects the oral cavity of the mucosal epithelium layer. Withanolides are a structurally related family of natural products extracted from the herbal plant (Withania genus). Many active members of this family play a major role in the prevention and cure of OSCC, while some also show potent activity as anticancer agents. The data covered by this review were collected from different databases, including PubMed, Scopus, and Web of Science, focusing on studies relevant to withanolides and their applications against oral squamous cell carcinoma from 2020 to 2025. The core structure of withanolides consists of a steroidal ring system along with a lactone moiety. Presently, more than 1200 withanolides with different lactones and an array of different functional groups have been identified. This article focuses on several key derivatives, elucidating their targets and signalling molecular pathways that modulate cellular survival, proliferation, invasion, and metastasis. As an example, withaferin A (WA) is a well-studied withanolide that exhibits potent anticancer effects in oral squamous cell carcinoma. WA has been shown to modulate key signalling pathways such as NF-κB, PI3K/Akt, and heat shock protein regulation, leading to apoptosis, autophagy, and cell cycle arrest. The classification of this large family of withanolides is presented, based on structural differences correlated with their anticancer effects, molecular targets, and signalling pathways. Additionally, the potential of these derivatives in enhancing therapeutic strategies and overcoming resistance to conventional treatments is described and summarized. By understanding the intricate mechanisms through which withanolides exert their effects, future research can develop novel cancer therapies that leverage the efficacy of these natural compounds.