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 determined considering the traditional method of its consumption by biting/chewing of the sclerotium.
Experimental approach. Mushroom sclerotial powder of cultivar TM02® was extracted and fractionated by in a 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 tumour necrosis factor (TNF) pathway was investigated.
Results and conclusions. 2,5-Diphenyl-2H-tetrazolium bromide (MTT) proliferation assay indicated that cell lines ORL-48 (derived from gingiva), ORL-188 (derived from the tongue) and ORL-204 (derived from buccal mucosa) were inhibited by cold water extract of L. rhinocerus sclerotia and its high-molecular-mass fraction (HMM) in varying degrees with ORL-204 being most affected. Hence, the treatment of ORL-204 with HMM mushroom extract was further investigated. HMM mushroom extract 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 mushroom extract-treated ORL-204 cells.
Novelty and scientific contribution. Using ORL-204, we showed that HMM mushroom extract may act via the TNF pathway at various network sites as a potential dietary compound for cancer prevention and natural adjunct therapeutic to conventional cancer treatment.