Page 56 - TD-4-2

Tumor Discovery Role of honokiol in combination therapy

aimed at preventing graft rejection. These therapies, while Honokiol has demonstrated potential as an adjuvant
essential for transplant success, compromise immune therapy to mitigate the increased cancer risk associated
surveillance and increase susceptibility to oncogenic with post-transplant immunosuppression. Its anti-
viruses and malignancies such as skin cancers, Kaposi inflammatory, antiproliferative, and immunomodulatory
sarcoma, and lymphomas, including post-transplant properties make it an attractive candidate for integration
lymphoproliferative disorders Oncogenic viruses, into post-transplant cancer prevention strategies.
67
such as Epstein-Barr virus, human papillomavirus, and
human herpesvirus 8 are frequently implicated in these 6.1. Cyclosporine A and honokiol
malignancies. 68,69 Other factors, such as recipient age at the Cyclosporine A (CsA) is a calcineurin inhibitor widely
time of transplantation, gender, and genetic pre-disposition, used to prevent transplant rejection. It blocks the
further modulate cancer risk. 70,71 The present management translocation of the nuclear factor of activated T cells to
strategies emphasize regular cancer screening, modulation the nucleus, suppressing T cell activation and immune
of immunosuppressive regimens, targeted therapies, and responses. However, CsA also promotes tumor progression
vaccinations against oncogenic viruses. 72,73 by activating oncogenic pathways such as Ras-Raf-ERK

Table 1. Combination treatments with honokiol

Drug/therapeutic name Cancer type/models Key findings References
Chemotherapeutic drugs
Cisplatin Colorectal cancer, ovarian Reduce toxicity, re-sensitization, interleukin-6/STAT3 regulation, 19,28-34
cancer, oral cancer, lung cancer, dynamin-related protein 1 regulation, and reactive oxygen species and
and renal cell carcinoma anti-oxidative enzyme regulation
Paclitaxel (Taxol) Human squamous KB cells, lung Inhibit cell proliferation and tumor growth, induce paraptosis, 19,37-40
cancer, and breast cancer downregulation of focal adhesion kinase, PI3K, MMP-2, and MMP-9
Doxorubicin Breast cancer and Inhibit growth and proliferation by regulating microRNA-188-5p, FBXW7, 42-45
cardiomyopathy and c-Myc, regulation of mucin 1 and multidrug resistance protein 1, and
cardioprotective properties
5‐fluorouracil Oral cancer, urothelial cell High apoptosis, suppresses tumor growth, cell cycle arrest, and decreased 47-49
carcinoma, and tongue cancer systemic toxicity
Metformin Breast cancer Induce apoptosis and inhibit cell growth 50
Bleomycin Breast cancer, pancreatic cancer, Reduce pulmonary toxicity and inhibit DNA repair 52
and melanoma
Monoclonal antibodies
Cetuximab Cetuximab-resistant cancer cells Resensitization, regulate HER, MAPK, AKT, and dynamin-related protein 53
1 pathways
Small-molecule inhibitors
Cabozantinib Renal cell carcinoma Induce reactive oxygen species-mediated apoptosis and autophagy, inhibit 57
Rubicon, p62, and HO-1
Lapatinib Breast cancer Cell cycle arrest induces apoptosis, suppresses PI3K/AKT/mTOR pathway 24
Imatinib Leukemia Inhibit cell adhesion to the extracellular matrix and induce paraptosis 59
Erlotinib Head and neck squamous cell Induce apoptosis, inhibit EGFR signaling pathways, including MAPK, 56,60
carcinoma and lung cancer AKT, and STAT3
Osimertinib Non-small cell lung cancer Inhibit cell proliferation and induce apoptosis, suppress tumor growth 61
even with 19del, T790M, and C797S triple mutations, inhibit p-ERK1/2,
and promote myeloid cell leukemia-1 degradation
Immunosuppressive drugs in transplantation
Cyclosporine A Renal cell carcinoma Inhibit cyclosporine A-induced Ras-Raf-ERK and VEGF pathways 74
Rapamycin Renal cell carcinoma Inhibit cell proliferation and growth, inhibit Rubicon, programmed 26,77
death-ligand 1, c-mesenchymal-epithelial transition factor, and AXL, and
downregulate HO-1
Abbreviations: AKT: Protein kinase B; EGFR: Epidermal growth factor receptor; ERK: Extracellular signal-regulated kinase; HER: Human epidermal
growth factor receptor; HO-1: Heme oxygenase-1; MAPK: Mitogen-activated protein kinase; MMP: Matrix metallopeptidase; mTOR: Mammalian target
of rapamycin; PI3K: Phosphoinositide 3-kinase; STAT3: Signal transducer and activator of transcription 3; VEGF: Vascular endothelial growth factor.

Volume 4 Issue 2 (2025) 48 doi: 10.36922/td.8152