Immunomodulatory Effect and an Intervention of TNF Signalling Leading to Apoptotic and Cell Cycle Arrest on ORL-204 Oral Cancer Cells by Tiger Milk Mushroom, Lignosus rhinocerus
1Department of Oral Biology and Biomedical Sciences, Faculty of Dentistry, MAHSA University, Jalan SP 2, Bandar Saujana Putra, 42610 Jenjarom, Selangor, Malaysia
2Medicinal Mushroom Research Group (MMRG), Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
3Department of Biomedical Sciences, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
4Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, MAHSA University, Jalan SP 2, Bandar Saujana Putra, 42610 Jenjarom, Selangor, Malaysia
5Oral Cancer Research and Coordinator (OCRCC), Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
6Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
7LiGNO Biotech Sdn. Bhd., Jalan Perindustrian Balakong Jaya 2/2, Taman Perindustrian Balakong Jaya 2, 43300 Balakong Jaya, Selangor, Malaysia
Received: 26 April 2021
Accepted: 14 November 2021
Lignosus rhinocerus; oral cancer; apoptosis; cell cycle; COX-2; MIP2
Research background. Tiger milk mushroom (Lignosus rhinocerus) is a medicinal mushroom that is geographically distributed in the region of South China, Thailand, Malaysia, Indonesia, Philippines and Papua New Guinea. Consumption of its sclerotium has been reported to treat various ailments. However, its anticancer potential towards oral cancer cell lines is yet to be discovered considering its traditional method of consumption by biting/chewing of the sclerotium.
Experimental approach. Mushroom sclerotial powder of cultivar TM02® was extracted and fractionated by a Sephadex G-50 chromatographic column prior to cytotoxicity testing against a panel of human oral cancer cell lines. The capability of the identified bioactive fraction in regulating several molecules associated with its TNF pathway was investigated.
Results and conclusions. MTT proliferation assay indicated that ORL-48 (derived from gingiva), ORL-188 (derived from the tongue), and ORL-204 (derived from buccal mucosa) were inhibited by L. rhinocerus sclerotial cold water extract and its high-molecular-mass fraction (HMM) in varying degree with ORL-204 being most affected. Hence, HMM treatment on ORL-204 was further investigated. HMM induced apoptosis and G0/G1-phase cell cycle arrest through caspase-3/7 cleavage. Activities of MIP2 and COX-2 were downregulated by 0.2- and 4.6-fold respectively in the HMM-treated ORL-204 cells.
Novelty and scientific contribution. Using ORL-204, it revealed that HMM may have intervened via the TNF pathway at various network sites in its manifestation as a potential dietary compound for cancer prevention and natural adjunct therapeutic to conventional cancer treatment.