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Tumor Discovery Role of honokiol in combination therapy

Similarly, Lu et al. demonstrated that paclitaxel tongue carcinoma induced by 4-nitroquinoline oxide in
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combined with honokiol nanosuspensions, encapsulated Wistar albino rats. Notably, this combination therapy also
in thermosensitive hydrogels, allowed for sustained and decreased systemic toxicity compared to either treatment
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targeted drug release at the tumor site. Honokiol has also alone. These findings suggest that honokiol can potentiate
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shown benefits as a complementary therapy in patients the anti-tumor effects of 5-FU while mitigating its adverse
with paclitaxel-resistant tumors, particularly when effects, making it a potential adjunct in cancer therapy.
administered intravenously. 19
2.5. Metformin and honokiol
2.3. Doxorubicin and honokiol Metformin, an established anti-diabetic medication, has
Doxorubicin, a potent chemotherapeutic agent used for gained attention for its potential anticancer effects. By
advanced-stage cancers, is known for its high toxicity, lowering systemic glucose levels, metformin limits the
particularly cardiotoxicity. To mitigate these effects, energy supply available to cancer cells, thereby inhibiting
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doxorubicin is often administered in combination their growth and proliferation. Studies have shown that
with other agents to enhance efficacy while reducing combining metformin with honokiol yields promising
toxicity. 42,43 Studies have investigated the combination of synergistic effects. In hormone-resistant breast cancer cells
doxorubicin and honokiol, which has shown promise in (MCF7/HT), the combination of honokiol and metformin
complementing doxorubicin’s anticancer effects while effectively inhibited cell proliferation and induced
mitigating cardiotoxicity. Honokiol has been shown to apoptosis. This suggests that the dual treatment may
reverse doxorubicin resistance in human breast cancer cells overcome resistance mechanisms common in hormone-
by targeting a molecular pathway involving microRNA- independent breast cancers, enhancing therapeutic
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188-5p, FBXW7, and c-Myc. Honokiol increases the efficacy. These findings highlight the potential of
expression of microRNA-188-5p, which upregulates honokiol and metformin as a combination strategy to
FBXW7, a tumor suppressor gene that downregulates c-Myc, exploit metabolic vulnerabilities in cancer cells. Further
effectively reversing drug resistance and inhibiting tumor research could establish this regimen as a viable therapeutic
growth. Moreover, honokiol enhances doxorubicin’s approach for hormone-resistant cancers.
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efficacy by regulating mucin 1 and multidrug resistance 2.6. Bleomycin and honokiol
protein 1, further improving its therapeutic effects and
reducing the likelihood of resistance. Importantly, Bleomycin is an important chemotherapeutic agent used
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honokiol’s cardioprotective properties provide a significant in the treatment of Hodgkin lymphoma and testicular
advantage, offering a safer combination therapy for patients germ-cell tumors, two of the most curable cancers.
receiving doxorubicin. However, its clinical application is frequently limited by
serious pulmonary side effects, including hypersensitivity
2.4. 5‐Fluorouracil (5-FU) and honokiol pneumonitis, bronchiolitis obliterans organizing
5-FU, a pyrimidine analog, is a widely used pneumonia, acute interstitial pneumonia, and progressive
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chemotherapeutic agent that inhibits nucleic acid synthesis, pulmonary fibrosis. Combining honokiol and bleomycin
thereby suppressing cancer cell growth and proliferation. has enhanced anticancer efficacy while potentially reducing
However, its clinical utility is often limited by toxicity and toxicity. In breast cancer (MCF7), pancreatic cancer
resistance. 46 (PANC-1), and melanoma (UACC903) cell lines, honokiol
reduced the effective concentration of bleomycin by tenfold.
Several studies have explored the combination of 5-FU This enhanced potency is attributed to honokiol’s ability to
with honokiol, demonstrating enhanced efficacy and inhibit the repair of bleomycin-induced single- and double-
reduced side effects. Ji et al. investigated this combination strand DNA damage, thereby promoting cancer cell death.
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in oral squamous cell carcinoma cells and in vivo models. By enabling lower therapeutic doses of bleomycin, this
Their findings revealed that the combination induced combination may help minimize pulmonary side effects
significantly higher levels of apoptosis and suppressed while maintaining or improving anticancer activity. These
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tumor growth more effectively than either agent alone. 47 findings suggest that honokiol could serve as an effective
Similarly, honokiol induced apoptosis in human adjuvant to bleomycin-based chemotherapy.
urothelial cell carcinoma cells and caused G0/G1 cell cycle 3. Monoclonal antibody and honokiol
arrest. When combined with 5-FU, honokiol exhibited
a synergistic effect, further enhancing the therapeutic combination
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response. Swidan et al. reported that combining 5-FU Monoclonal antibodies have revolutionized cancer
and nanoparticulated honokiol significantly reduced therapy by targeting tumor-associated antigens, improving
Volume 4 Issue 2 (2025) 45 doi: 10.36922/td.8152