Honokiol: Synergistic Effects with Other Cancer Treatments

One of honokiolís most promising benefits is its ability to synergize with other cancer treatments. Clinical trials are desperately needed to validate the potential synergy that has been demonstrated in vitro and in vivo.


A 2013 in vitro study published in the International Journal of Oncology showed that honokiol synergized chemotherapy drugs in multidrug resistant (MDR) breast cancer.[1] A 2011 in vitro study published in PLoS One found that honokiol enhanced the apoptotic effects of the anticancer drug gemcitabine against pancreatic cancer.[2]

In vivo research published in Oncology Letters in 2011 found honokiol enhanced the action of cisplatin against colon cancer.[3]

A 2010 in vitro study from the Journal of Biological Regulators and Homeostatic Agents showed that honokiol resensitized cancer cells to doxorubicin in multidrug resistant uterine cancer.[4]

A 2010 in vitro study published in Toxicology Mechanisms and Methods showed honokiol performed synergistically with the drug imatinib against human leukemia cells.[5]

2008 in vivo research published in the International Journal of Gynecological Cancer showed honokiol to potentiate the activity of cisplatin in murine models of ovarian cancer.[6]

2005 in vitro research published in Blood showed honokiol enhanced the cytotoxicity induced by fludarabine, cladribine, and chlorambucil, indicating it is a potent inducer of apoptosis in B-CLL cells.[7]

Radiation treatment

2012 in vitro research published in Molecular Cancer Therapeutics showed that honokiol was able to sensitize cancer cells to radiation treatments.[8] A 2011 in vitro study published in American Journal of Physiology Gastrointestinal and Liver Physiology showed honokiol sensitized treatment-resistant colon cancer cells to radiation therapy.[9]


1. Tian W, Deng Y, Li L, He H, Sun J, Xu D. Honokiol synergizes chemotherapy drugs in multidrug resistant breast cancer cells via enhanced apoptosis and additional programmed necrotic death. Int J Oncol. 2013;42(2):721-732.
2. Arora S, Bhardwaj A, Srivastava SK, et al. Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells. PLoS One. 2011;6(6): e21573.
3. Cheng N, Xia T, Han Y, He QJ, Zhao R, Ma JR. Synergistic antitumor effects of liposomal honokiol combined with cisplatin in colon cancer models. Oncol Lett. 2011;2(5):957-962.
4. Angelini A, Di Ilio C, Castellani ML, Conti P, Cuccurullo F. Modulation of multidrug resistance p-glycoprotein activity by flavonoids and honokiol in human doxorubicin-resistant sarcoma cells (MES-SA/DX-5): implications for natural sedatives as chemosensitizing agents in cancer therapy. J Biol Regul Homeost Agents. 2010;24(2):197-205.
5. Wang Y, Yang Z, Zhao Z. Honokiol induces parapoptosis and apoptosis and exhibits schedule-dependent synergy in combination with imatinib in human leukemia cells. Toxicol Mech Methods. 2010;20(5):234-241.
6. Liu Y, Chen L, He X, et al. Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma. Int J Gynecol Cancer. 2008;18(4):652-659.
7. Battle TE, Arbiser J, Frank DA. The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Blood. 2005;106(2):690-697.
8. Ponnurangam S, Mammen JM, Ramalingam S, et al. Honokiol in combination with radiation targets notch signaling to inhibit colon cancer stem cells. Mol Cancer Ther. 2012;11(4):963-972.
9. He Z, Subramaniam D, Ramalingam S, et al. Honokiol radiosensitizes colorectal cancer cells: enhanced activity in cells with mismatch repair defects. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G929-37.

Effect of honokiol on activity of GAD65 and GAD67 in the cortex and hippocampus of mice

Honokiol, an active agent extracted from magnolia bark, has been reported that induces anxiolytic action in a mouse elevated plus-maze test. However, the mechanism of anxiolytic action induced by honokiol remains unclear. This study was to investigate the change in two forms of glutamic acid decarboxylase (GABA synthesized enzymes) GAD65 and GAD67 in the cortex and hippocampus areas while the anxiolytic actions induced by chronic administration of honokiol in mice. Mice treated with 7 daily injection of honokiol (1mg/kg, p.o.) caused anxiolytic action which was similar to that was induced by 7 daily injection of diazepam (2mg/kg, p.o.) in the elevated plus-maze test. In addition, the activity of hippocampal GAD65 of honokiol treated mice was significantly increased than that of the vehicle or diazepam treated groups. These data suggest that honokiol causes diazepam-like anxiolytic action, which may be mediated by altering the synthesis of GABA in the brain of mice.

Ku T-H, Lee Y-J, Wang S-J, Fan C-H, & Tien L-T. Effect of honokiol on activity of GAD65 and GAD67 in the cortex and hippocampus of mice. Phytomedicine. 2011 doi:10.1016/j.phymed.2011.03.007
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