A critical assessment for huaier, a traditional Chinese medicine, for cancer therapy: medicinal characteristics, molecular mechanisms of action, in-vitro and in-vivo anticancer activities, and future research directions

Cancer, a pervasive global health concern, remains a leading cause of mortality worldwide. Current cancer treatment modalities encompass surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy, all of which have significantly contributed to improving patient survival. However, these treatments are often accompanied by significant side effects, immunotherapy resistance, and limited efficacy in advanced stages. In this context, traditional Chinese medicine (TCM) has emerged as a potential adjunct therapy for cancer, offering multitarget effects and minimal side effects. Huaier (Trametes robiniophila Murr), a traditional Chinese herbal extract with a history spanning over a thousand years, has garnered significant attention for its anticancer properties.

Chemical Composition and Extraction Methods
Huaier's chemical composition primarily comprises polysaccharides, sterols, and alkaloids. Polysaccharides, the primary active component, are long-chain polymers of monosaccharides and have shown profound pharmacological activities, including antitumor effects. The extraction of Huaier polysaccharides (HPs) can be achieved through various methods, including water extraction, acid extraction, alkali extraction, salt precipitation, enzyme extraction, ultrasonic-assisted extraction, and supercritical fluid extraction. Each method impacts the extraction efficiency and biological activity of HPs, with water extraction being the most commonly employed due to its simplicity and effectiveness.

Medicinal Characteristics and Clinical Applications
Huaier has been traditionally used in TCM for its numerous health benefits, including hemostasis, treatment of intestinal hemorrhoids, nourishing Yin, moistening dryness, nourishing the heart, alleviating anxiety and insomnia, tonifying qi, strengthening the spleen, improving appetite, and moistening the lungs to relieve dry cough. In modern medicine, Huaier was first clinically used in the treatment of advanced liver cancer in the 1980s and was subsequently approved for this indication in China in 1992. Its unique anticancer effect has since been explored across various cancer types, such as breast cancer, lung cancer, liver cancer, and colon cancer.

Molecular Mechanisms of Action
The anticancer mechanisms of Huaier are multifaceted and involve multiple pathways. It inhibits tumor cell proliferation, promotes apoptosis, induces oxidative stress, interferes with cell cycle arrest, inhibits tumor metastasis and angiogenesis, induces autophagy, and regulates immune function. Huaier has been shown to modulate key signaling pathways, including PI3K/Akt/mTOR, MAPK, NF-kB, and JAK/STAT, resulting in cell cycle arrest and apoptosis. Furthermore, it enhances the immune system by stimulating cytokine production and enhancing the activity of natural killer cells and macrophages.

In-Vitro and In-Vivo Anticancer Activities
Numerous in-vitro and in-vivo studies have demonstrated Huaier's potent antitumor effects. In-vitro studies have shown that Huaier inhibits the proliferation of various cancer cell lines and induces apoptosis through various mechanisms. In-vivo studies and clinical trials have further confirmed Huaier's ability to slow tumor progression, reverse drug resistance, improve chemotherapy drug sensitivity, and extend cancer patients' survival time. Huaier has also been shown to have synergistic effects when combined with conventional chemotherapy, enhancing its efficacy and reducing toxicity.

Future Research Directions
Despite the promising results of Huaier in cancer therapy, further research is needed to fully elucidate its anticancer mechanisms and efficacy. Future studies should focus on identifying the active ingredients responsible for Huaier's anticancer effects and their specific targets. Additionally, clinical trials with larger sample sizes and longer follow-up periods are required to validate Huaier's efficacy and safety in various cancer types. Furthermore, research on the combination of Huaier with other anticancer agents, including immunotherapy and targeted therapy, holds immense potential for improving cancer treatment outcomes.

Conclusions
In conclusion, Huaier, a traditional Chinese medicine with a rich history, has shown significant potential as an anticancer agent. Its unique multitarget effects and minimal side effects make it an attractive adjunct therapy for cancer. Further research is necessary to fully understand its molecular mechanisms and efficacy, with the aim of developing novel anticancer drugs and treatment strategies. The integration of Huaier into cancer treatment protocols may lead to improved outcomes and quality of life for cancer patients.

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https://www.xiahepublishing.com/2996-3427/OnA-2024-00007

The study was recently published in the Oncology Advances.

Oncology Advances is dedicated to improving the diagnosis and treatment of human malignancies, advancing the understanding of molecular mechanisms underlying oncogenesis, and promoting translation from bench to bedside of oncological sciences. The aim of Oncology Advances is to publish peer-reviewed, high-quality articles in all aspects of translational and clinical studies on human cancers, as well as cutting-edge preclinical and clinical research of novel cancer therapies.

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