Ng, Min Jia and Kong, Boon Hong and Teoh, Kean Hooi and Yap, Yeannie Hui-Yeng and Ng, Szu Ting and Tan, Chon Seng and Razif, Muhammad Fazril Mohamad and Fung, Shin Yee (2023) In vivo anti-tumor activity of Lignosus rhinocerus TM02 (R) using a MCF7-xenograft NCr nude mice model. Journal of Ethnopharmacology, 304. ISSN 0378-8741, DOI https://doi.org/10.1016/j.jep.2022.115957.
Full text not available from this repository.Abstract
Ethnopharmacological relevance: Lignosus rhinocerus (Cooke) Ryvarden (also known as Tiger Milk mushroom, TMM), is a basidiomycete belonging to the Polyporaceae family. It has been documented to be used by tradi-tional Chinese physicians and indigenous people in Southeast Asia to treat a variety of illnesses, such as gastritis, arthritis, and respiratory conditions, as well as to restore patients' physical well-being. TMM has also been used in folk medicine to treat cancer. For example, people from the indigenous Kensiu tribe of northeast Kedah (Malaysia) apply shredded TMM sclerotium mixed with water directly onto breast skin to treat breast cancer, while Chinese practitioners from Hong Kong, China prescribe TMM sclerotium as a treatment for liver cancer. L. rhinocerus has previously been demonstrated to possess selective anti-proliferative properties in vitro, however pre-clinical in vivo research has not yet been conducted.Aim of study: This study aimed to examine the anti-tumor activities of L. rhinocerus TM02 (R), using two different sample preparations cold water extract (CWE) and fraction] via various routes of administration (oral and intraperitoneal) on an MCF7-xenograft nude mouse model. This study also investigated the inhibitory effect of TM02 (R) CWE and its fractions against COX-2 in vitro using LPS-induced RAW264.7 macrophages, on the basis of the relationship between COX-2 and metastasis, apoptosis resistance, as well as the proliferation of cancer cells. Materials and methods: The first preparation, L. rhinocerus TM02 (R) sclerotium powder (TSP) was dissolved in cold water to obtain the cold water extract (CWE). It was further fractionated based on its molecular weight to obtain the high (HMW), medium (MMW) and low (LMW) molecular weight fractions. The second preparation, known as the TM02 (R) rhinoprolycan fraction (TRF), was obtained by combining the HMW and MMW fractions. TSP was given orally to mimic the daily consumption of a supplement; TRF was administered intraperitoneally to mimic typical tumorous cancer treatment with a rapid and more thorough absorption through the peritoneal cavity. Another experiment was conducted to examine changes in COX-2 activity in LPS-induced RAW264.7 macro-phages after a 1-h pre-treatment with CWE, HMW, and MMW.Results: Our results revealed that intraperitoneal TRF-injection (90 mu g/g BW) for 20 days reduced initial tumor volume by similar to 64.3% (n = 5). The percentage of apoptotic cells was marginally higher in TRF-treated mice vs. control, suggesting that induction of apoptosis as one of the factors that led to tumor shrinkage. TSP (500 mu g/g BW) oral treatment (n = 5) for 63 days (inclusive of pre-treatment prior to tumor inoculation) effectively inhibited tumor growth. Four of the five tumors totally regressed, demonstrating the effectiveness of TSP ingestion in suppressing tumor growth. Although no significant changes were found in mouse serum cytokines (TNF-alpha, IL-5, IL-6 and CCL2), some increasing and decreasing trends were observed. This may suggest the immunomodulatory potential of these treatments that can directly or indirectly affect tumor growth. Pre-treatment with CWE, HMW and MMW significantly reduced COX-2 activity in RAW264.7 macrophages upon 24 h LPS-stimulation, suggesting the potential of L. rhinocerus TM02 (R) extract and fractions in regulating M1/M2 polarization.Conclusion: Based on the findings of our investigation, both the rhinoprolycan fraction and crude sclerotial powder from L. rhinocerus TM02 (R) demonstrated tumor suppressive effects, indicating that they contain substances with strong anticancer potential. The antitumor effects of L. rhinocerus TM02 (R) in our study highlights the potential for further explorations into its mechanism of action and future development as a prophylactic or adjunct thera-peutic against tumorous cancer.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education Malaysia via the Fundamental Research Grant Scheme [Grant No: FRGS/1/2020/STG02/UM/02/1] |
| Uncontrolled Keywords: | Lignosus rhinocerusTM02 (R); In vivo; Tumor suppression; Apoptosis; COX-2 inhibition; Immunomodulation |
| Subjects: | R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 27 Nov 2024 04:11 |
| Last Modified: | 27 Nov 2024 06:48 |
| URI: | http://eprints.um.edu.my/id/eprint/39198 |
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