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Background <p>Metal-based therapeutics are re-emerging in oncology, exemplified by the discovery of copper-dependent cell death pathways, such as cuproptosis, and by the use of arsenic trioxide in leukemia. Traditional Siddha herbo-mineral formulations employ systematic sulphidation and calcination processes that convert metals into chemically stable, low-solubility forms, potentially modifying their biological activity and toxicity.</p> Purpose of the Review <p>This review aims to critically synthesize classical Siddha knowledge and contemporary scientific evidence on the metallurgical transformation, molecular mechanisms, anticancer potential, and safety considerations of <i>Siva Thambira Chenduram</i> (STC), a Siddha formulation composed of mercuric sulphide (HgS), copper sulphide (CuS), arsenic sulphides (As₂S₃/As₄S₄), and elemental sulphur. A narrative synthesis of peer-reviewed experimental and clinical studies was conducted alongside classical Siddha texts, focusing on physicochemical transformation, nanoscale characteristics, and mechanistic pathways relevant to cancer biology.</p> Recent Findings <p>Available evidence indicates that ingredients of STC exert multi-pathway anticancer effects. Copper sulphide has been reported to induce copper-dependent metabolic stress in experimental systems. Whether copper sulphide within STC undergoes selective dissolution or intracellular activation under tumor microenvironmental conditions remains unknown and warrants investigation. While arsenic sulphides induce mitochondrial apoptosis through Bax/Bcl-2 modulation, p53 activation, and caspase signaling. Elemental sulphur contributes to redox imbalance and suppression of pro-survival and metastatic pathways, including Akt, ErbB, and Matrix Metalloproteinases (MMP). Mercuric sulphide predominantly exists as a chemically stable, low-bioavailability phase, potentially limiting systemic mercury toxicity while contributing to nanoscale structural integrity.</p> Summary <p>STC represents a hypothesis-generating, multi-target complex with potential translational relevance in oncology. Future progress requires standardized manufacturing, rigorous physicochemical and toxicological evaluation, and well-controlled clinical studies to establish its safety and therapeutic role.</p>

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Mercury and Copper-based Complex Sulphide (Siva Thambira Chenduram) in Contemporary Oncology: A Review of Metallurgical Composition, Transformation, and Relevance to Cancer

  • 期刊论文

  • 发表日期：

    2026年7月6日

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  • Abarna Balasubramani,
  • Ganapathi R,
  • R. Sathish Adithya,
  • Murugesan Sannasi,
  • Madhavan Ramachandran,
  • Senthil Vel G

摘要

Background

Metal-based therapeutics are re-emerging in oncology, exemplified by the discovery of copper-dependent cell death pathways, such as cuproptosis, and by the use of arsenic trioxide in leukemia. Traditional Siddha herbo-mineral formulations employ systematic sulphidation and calcination processes that convert metals into chemically stable, low-solubility forms, potentially modifying their biological activity and toxicity.

Purpose of the Review

This review aims to critically synthesize classical Siddha knowledge and contemporary scientific evidence on the metallurgical transformation, molecular mechanisms, anticancer potential, and safety considerations of Siva Thambira Chenduram (STC), a Siddha formulation composed of mercuric sulphide (HgS), copper sulphide (CuS), arsenic sulphides (As₂S₃/As₄S₄), and elemental sulphur. A narrative synthesis of peer-reviewed experimental and clinical studies was conducted alongside classical Siddha texts, focusing on physicochemical transformation, nanoscale characteristics, and mechanistic pathways relevant to cancer biology.

Recent Findings

Available evidence indicates that ingredients of STC exert multi-pathway anticancer effects. Copper sulphide has been reported to induce copper-dependent metabolic stress in experimental systems. Whether copper sulphide within STC undergoes selective dissolution or intracellular activation under tumor microenvironmental conditions remains unknown and warrants investigation. While arsenic sulphides induce mitochondrial apoptosis through Bax/Bcl-2 modulation, p53 activation, and caspase signaling. Elemental sulphur contributes to redox imbalance and suppression of pro-survival and metastatic pathways, including Akt, ErbB, and Matrix Metalloproteinases (MMP). Mercuric sulphide predominantly exists as a chemically stable, low-bioavailability phase, potentially limiting systemic mercury toxicity while contributing to nanoscale structural integrity.

Summary

STC represents a hypothesis-generating, multi-target complex with potential translational relevance in oncology. Future progress requires standardized manufacturing, rigorous physicochemical and toxicological evaluation, and well-controlled clinical studies to establish its safety and therapeutic role.