Category Archives: Depression or Anxiety

Akt, angiogenesis, Anti-cancer, anti-inflammatory, Anti-metastatic, anti-proliferative, apoptosis, Apoptotic, ARO, Autophagy, Autophagy inhibitor, BAX, Bcl-2, Breast cancer, Breast cancer cell lines, CDK6, cell-cycle arrest, Chapter 7 Isolates and Cancer Research, Colon Cancer or Colorectal cancer, cytotoxic, Depression or Anxiety, Down-regulates, DU145 and PC3, ER, ER-negative, Evodia rutaecarpa, G0/G1, G1, G2/M, IKK, increases intracellular ROS, inflammation, inhibits metastasis, inhibits NF-κB, Lung cancer, MCF-7 and MDA-MB-231, MDR, MTOR, Nitric Oxide, Pancreatic cancer, PI3K, PI3K/Akt, PTEN, ROS, SGC7901, TNF

Evodiamine

Cancer: Pancreatic, gastric, breast; ER+, ER-, lung

Action: Inhibits NF- κB, inhibits metastasis, increases intracellular ROS, apoptosis, cell-cycle arrest, anti-cancer, MDR

Evodiamine, a naturally occurring indole alkaloid, is one of the main bioactive ingredients of Evodia rutaecarpa [(Juss.) Benth.] (alkaloidal component of the extract). With respect to the pharmacological actions of evodiamine, more attention has been paid to beneficial effects in insults involving cancer, obesity, nociception, inflammation, cardiovascular diseases, Alzheimer's disease, infectious diseases and thermo-regulative effects. Evodiamine has evolved a superior ability to bind various proteins (Yu et al., 2013). Evodiamine exhibits anti-proliferative, anti-metastatic, and apoptotic activities.

Anti-cancer, MDR

Evodiamine possesses anti-anxiety, anti-obesity, anti-nociceptive, anti-inflammatory, anti-allergic, and anti-cancer effects. As well, it has thermoregulation, protection of myocardial ischemia-reperfusion injury and vessel-relaxing activities (Kobayashi, 2003; Shin et al., 2007; Ko et al., 2007; Ji, 2011). Evodiamine exhibits anti-cancer activities both in vitro and in vivo by inducing cell-cycle arrest or apoptosis, and inhibiting angiogenesis, invasion, and metastasis in a variety of cancer cell lines (Ogasawara et al., 2001; Ogasawara et al., 2002; Fei et al., 2003; Shyu et al., 2006). It presents anti-cancer potentials at micromolar concentrations and even at the nanomolar level in some cell lines in vitro (Lee et al., 2006; Wang, Li, & Wang, 2010). Evodiamine also stimulates autophagy, which serves as a survival function (Yang et al., 2008). Compared with other compounds, evodiamine is less toxic to normal human cells, such as human peripheral blood mononuclear cells (Fei et al., 2003; Zhang et al., 2004). It also inhibits the proliferation of adriamycin-resistant human breast cancer NCI/ADR-RES cells both in vitro and in Balb-c/nude mice (Liao et al., 2005).

Lung Cancer, Cell-cycle Arrest

Evodiamine (10  mg/kg) administrated orally twice daily significantly inhibits   tumor growth (Liao et al., 2005). Moreover, treatment with 10 mg/kg evodiamine from the 6th day after tumor inoculation into mice reduces lung metastasis and does not affect the body weight of mice during the experimental period (Ogasawara et al., 2001).

Cell-cycle Arrest

Evodiamine inhibits TopI enzyme, forms the DNA covalent complex with a similar concentration to that of irinotecan, and induces DNA damage (Chan et al., 2009; Tsai et al., 2010; Dong et al., 2010). However, TopI may not be the main target of this compound. Cancer cells treated with evodiamine exhibit G 2 / M phase arrest (Kan et al., 2004; Huang et al., 2004; Liao et al., 2005) rather than S phase arrest, which is not consistent with the mechanism of classic TopI inhibitors, such as irinotecan. Therefore, other targets aside from TopI may also be important for realizing the anti-cancer potentials of evodiamine. This statement is supported by the fact that evodiamine has effects on tubulin polymerization (Huang et al., 2004).

Increases Intracellular ROS, Apoptosis

Exposure to evodiamine rapidly increases intracellular ROS followed by an onset of mitochondrial depolarization (Yang et al., 2007). The generation of ROS and nitric oxide acts in synergy and triggers mitochondria-dependent apoptosis (Yang et al., 2008). Evodiamine also induces caspase-dependent and caspase-independent apoptosis, down-regulates Bcl-2 expression, and up-regulates Bax expression in some cancer cells (Zhang et al., 2003; Lee et al., 2006). The phosphatidylinositol 3-kinase/Akt/caspase and Fas ligand (Fas-L)/NF-κB signaling pathways might account for evodiamine-induced cell death. Moreover, these signals could be increased by the ubiquitin-proteasome pathway (Wang, Li, & Wang, 2010).

Inhibits Metastasis

Evodiamine has a marked inhibitory activity on tumor cell migration in vitro. When evodiamine at 10 mg/kg was administered into mice from the 6th day after tumor inoculation, the number of tumor nodules in lungs was decreased by 48% as compared to control. The inhibition rate was equivalent to that produced by cisplatin. Results suggest that evodiamine may be regarded as a promising agent in tumor metastasis therapy (Ogasawara et al., 2005).

Inhibits NF-κB

Evodiamine inhibited tumor necrosis factor (TNF)-induced Akt activation and its association with IKK. This down-regulation potentiated the apoptosis induced by cytokines and chemotherapeutic agents and suppressed TNF-induced invasive activity. Overall, these results indicate that evodiamine inhibits both constitutive and induced NF-κB activation and NF-κB-regulated gene expression (Takada et al., 2005).

Breast Cancer

Endocrine sensitivity, assessed by the expression of estrogen receptor (ER), has long been the predict factor to guide therapeutic decisions. Tamoxifen has been the most successful hormonal treatment in endocrine-sensitive breast cancer. However, in estrogen-insensitive cancer tamoxifen showed less effectiveness than in estrogen-sensitive cancer. It is interesting to develop new drugs against both hormone-sensitive and insensitive tumor. In this present study Wang et al. (2013) examined anti-cancer effects of evodiamine extracted from the Chinese herb, Evodiae fructus, in estrogen-dependent and -independent human breast cancer cells, MCF-7 and MDA-MB-231 cells, respectively.

Breast Cancer; ER+, ER-

The expression of ER α and β in protein and mRNA levels was down-regulated by evodiamine according to data from immunoblotting and RT-PCR analysis. Overall, results indicate that evodiamine mediates degradation of ER and induces caspase-dependent pathway leading to inhibition of proliferation of breast cancer cell lines. It suggests that evodiamine may in part mediate through ER-inhibitory pathway to inhibit breast cancer cell proliferation.

Evodiamine (10 mg/kg) significantly reduced tumor growth and pulmonary metastasis. In vitro, evodiamine inhibited cell migration and invasion abilities through down-regulation of MMP-9, urokinase-type plasminogen activator (uPA) and uPAR expression. Evodiamine-induced G0/G1 arrest and apoptosis were associated with a decrease in Bcl-2, cyclin D1 and cyclin-dependent kinase 6 (CDK6) expression and an increase in Bax and p27Kip1 expression (Du et al., 201).

Gastric Cancer

A study by Rasul et al. (2012) was conducted to investigate the synchronized role of autophagy and apoptosis in evodiamine-induced cytotoxic activity on SGC-7901 human gastric adenocarcinoma cells and further to elucidate the underlying molecular mechanisms. Evodiamine significantly inhibited the proliferation of SGC-7901 cells and induced G2/M phase cell-cycle arrest.

Evodiamine-induced autophagy is partially involved in the death of SGC-7901 cells which was confirmed by using the autophagy inhibitor 3-methyladenine (3-MA). Evodiamine has therapeutic potential against cancers.

Pancreatic Cancer

In vitro application of the combination therapy triggered significantly higher frequency of pancreatic cancer cells apoptosis, inhibited the activities of PI3K, Akt, PKA, mTOR and PTEN, and decreased the activation of NF-κB and expression of NF- κB-regulated products. Evodiamine can augment the therapeutic effect of gemcitabine in pancreatic cancer through direct or indirect negative regulation of the PI3K/Akt pathway (Wei et al., 2012).

References

Chan ALF, Chang WS, Chen LM et al. (2009). Evodiamine stabilizes topoisomerase I-DNA cleavable complex to inhibit topoisomerase I activity. Molecules, (14):4:1342–1352.


Dong G, Sheng C, Wang CS, et al. (2010). Selection of evodiamine as a novel topoisomerase i inhibitor by structure-based virtual screening and hit optimization of evodiamine derivatives as anti-tumor agents. Journal of Medicinal Chemistry, 53(21):7521–7531.


Du J, Wang XF, Zhou QM, et al. (2013). Evodiamine induces apoptosis and inhibits metastasis in MDA “American Typewriter”; “American Typewriter”;‑ MB-231 human breast cancer cells in vitro and in vivo. Oncol Rep, 30(2):685-94. doi: 10.3892/or.2013.2498.


Fei XF, Wang BX, T. Li TJ et al. (2003). Evodiamine, a constituent of Evodiae Fructus, induces anti-proliferating effects in tumor cells. Cancer Science, 94(1):92–98.


Huang YC, Guh JH, Teng CM. (2004). Induction of mitotic arrest and apoptosis by evodiamine in human leukemic T-lymphocytes. Life Sciences, 75(1):35–49.


Ji YB. (2011). Active Ingredients of Traditional Chinese Medicine: Pharmacology and Application. People's Medical Publishing House Co., LTD. Connecticut USA


Kan SF, Huang WJ, Lin LC, Wang PS. (2004). Inhibitory effects of evodiamine on the growth of human prostate cancer cell line LNCaP. International Journal of Cancer, 110(5):641–651.


Ko HC, Wang YH, Liou KT et al. (2007). Anti-inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells. European Journal of Pharmacology, 555(2-3):211–217.


Kobayashi Y. (2003). The nociceptive and anti-nociceptive effects of evodiamine from fruits of Evodia rutaecarpa in mice. Planta Medica, 69(5):425–428.


Lee TJ, Kim EJ, Kim S et al. (2006). Caspase-dependent and caspase-independent apoptosis induced by evodiamine in human leukemic U937 cells. Molecular Cancer Therapeutics, 5(9):2398–2407.


Liao CH, Pan SL, Guh JH et al. (2005). Anti-tumor mechanism of evodiamine, a constituent from Chinese herb Evodiae fructus, in human multiple-drug resistant breast cancer NCI/ADR-RES cells in vitro and in vivo. Carcinogenesis, 26(5):968–975.


Ogasawara M, Matsubara T, Suzuki H. (2001). Inhibitory effects of evodiamine on in vitro invasion and experimental lung metastasis of murine colon cancer cells. Biological and Pharmaceutical Bulletin, 24(8):917–920.


Ogasawara M, Matsunaga T, Takahashi S, Saiki I, Suzuki H. (2002). Anti-invasive and metastatic activities of evodiamine. Biological and Pharmaceutical Bulletin, 25(11):1491–1493.


Rasul A, Yu B, Zhong L, et al. (2012). Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy. Oncol Rep, 27(5):1481-7. doi: 10.3892/or.2012.1694


Shin YW, Bae EA, Cai XF, Lee JJ, and Kim DH. (2007). In vitro and in vivo antiallergic effect of the fructus of Evodia rutaecarpa and its constituents, Biological and Pharmaceutical Bulletin, 30(1):197–199, 2007.


Shyu KG, Lin S, Lee CC et al. (2006). Evodiamine inhibits in vitro angiogenesis: implication for anti-tumorgenicity. Life Sciences, 78(19):2234–2243.


Takada Y, Kobayashi Y, Aggarwal BB. (2005). Evodiamine Abolishes Constitutive and Inducible NF- κB Activation by Inhibiting IκBα Kinase Activation, Thereby Suppressing NF-κ B-regulated Antiapoptotic and Metastatic Gene Expression, Up-regulating Apoptosis, and Inhibiting Invasion. The Journal of Biological Chemistry, 280:17203-17212. doi: 10.1074/jbc.M500077200.


Tsai HP, Lin LW, Lai ZY et al. (2010). Immobilizing topoisomerase I on a surface plasmon resonance biosensor chip to screen for inhibitors. Journal of Biomedical Science, 17(1):49.


Wang C, Li S, Wang MW. (2010). Evodiamine-induced human melanoma A375-S2 cell death was mediated by PI3K/Akt/caspase and Fas-L/NF- κ B signaling pathways and augmented by ubiquitin-proteasome inhibition. Toxicology in Vitro, 24(3):898–904.


Wang KL, Hsia SM, Yeh JY, et al. (2013). Anti-Proliferative Effects of Evodiamine on Human Breast Cancer Cells. PLoS One, 8(6):e67297.


Wei WT, Chen H, Wang ZH, et al. (2012). Enhanced anti-tumor efficacy of gemcitabine by evodiamine on pancreatic cancer via regulating PI3K/Akt pathway. Int J Biol Sci, 8(1):1-14.


Yu H, Jin H, Gong W, Wang Z, Liang H. (2013). Pharmacological actions of multi-target-directed evodiamine. Molecules, 18(2):1826-43. doi: 10.3390/molecules18021826.


Yang J, Wu LJ, Tashino SI, et al. (2007). Critical roles of reactive oxygen species in mitochondrial permeability transition in mediating evodiamine-induced human melanoma A375-S2 cell apoptosis. Free Radical Research, 41(10):1099–1108.


Zhang Y, Wu LJ, Tashiro SI, Onodera S, Ikejima T. (2003). Intracellular regulation of evodiamine-induced A375-S2 cell death. Biological and Pharmaceutical Bulletin, 26(11):1543–1547.


Zhang Y, Zhang QH, Wu LJ, et al. (2004). Atypical apoptosis in L929 cells induced by evodiamine isolated from Evodia rutaecarpa. Journal of Asian Natural Products Research, 6(1):19–27.

A549 and CH27, angiogenesis, Anti-angiogenic, Anti-cancer, anti-depressant, anti-inflammatory, Anti-metastatic, anti-tumor, Antibiotic, anxiolytic, apoptosis, Apoptotic, B-CLL, Breast cancer, Chapter 7 Isolates and Cancer Research, Chemo-sensitizer, Chemotherapy, Colon Cancer or Colorectal cancer, cytotoxic, Depression or Anxiety, HL-60, induces apoptosis, inflammation, inhibits angiogenesis, inhibits VEGF, Lung cancer, MCF-7/ADR, MDR, Multi-Drug Resistance, Multi-drug resistance, Multi-drug resistance reversal, Ovarian cancer, Pancreatic cancer, Prostate cancer, radio-sensitizing, RKO, Sarcoma, STAT, Uterine cancer, VEGF, VEGF

Honokiol (See also Injectables)

Cancer:
Lung, breast, prostate, leukemia, colorectal., esophageal., ovarian, myeloma, pancreatic, stomach, uterine

Action: Anti-angiogenic, chemo-sensitizer, multi-drug resistance reversal., anti-inflammatory, anxiolytic, anti-depressant, inhibits VEGF, anti-metastatic, synergistic effects with other cancer treatments

Honokiol is a phenolic compound purified from plants of the Magnolia genus, including Magnolia officinalis (Rehder & Wilson) and Magnolia grandiflora (L.), that exhibits anti-cancer effects in experimental models with various types of cancer cells, including esophageal., ovarian, breast, and lung cancer, as well as myeloma and leukemia. It is speculated that this compound causes cancer cell death in part through targeting mitochondria (Munroe et al., 2007; Chen et al., 2009; Fried & Arbiser, 2009).

Inhibits Angiogenesis, MDR, Anti-inflammatory, Inhibits VEGF

Honokiol is one of two dominant biphenolic compounds isolated from Magnolia spp. bark, and is the most widely researched active constituent of the bark. In vivo studies suggest that honokiol's greatest value is in its multiple anti-cancer actions. In vitro research suggests honokiol has potential to enhance current anti-cancer regimens by inhibiting angiogenesis, promoting apoptosis, providing direct cytotoxic activity, down-regulating cancer cell signaling pathways, regulating genetic expression, enhancing the effects of specific chemotherapeutic agents, radio-sensitizing cancer cells to radiation therapy, and inhibiting multi-drug resistance.

Honokiol also shows potential in preventive health by reducing inflammation and oxidative stress, providing neurological protection, and regulating glucose; in mental illness by its effects against anxiety and depression; and in helping regulate stress response signaling. Its anti-microbial effects demonstrate potential for partnering with anti-viral/antibiotic therapy, and treating secondary infections.

Honokiol may occupy a distinct therapeutic niche because of its unique characteristics: the ability to cross the blood brain barrier (BBB) and blood cerebrospinal fluid barrier (BCSFB), high systemic bioavailability, and its actions on a multiplicity of signaling pathways and genomic activity. There is a need for research on honokiol to progress to human studies and on into clinical use.

The preclinical research on honokiol's broad-ranging capabilities shows its potential as a therapeutic compound for numerous solid and hematological cancers, including its effectiveness in combating multi-drug resistance (MDR) and its synergy with other anti-cancer therapies. Research thus far shows no toxicity or serious adverse effects in animal models.

Honokiol has also been shown to inhibit spread of cancer cells through the lymph system by inhibiting one of the primary pathways involved in growth stimulation related to vascular endothelial growth factor (VEGF) (Wen et al., 2009).

Inhibits Angiogenesis, Gastric Cancer

A 2012 in vivo study in PLoS One showed that honokiol, by inhibiting angiogenic pathways such as STAT-3, dampened peritoneal dissemination of gastric cancer in mice (5 mg/kg delivered intraperitoneally) (Liu et al., 2012).    

Induces Apoptosis; Leukemia

Honokiol induces cell apoptosis in several cell lines, such as leukemia cell lines HL-60, colon cancer cell lines RKO, lung cancer cell lines A549 and CH27 (Hirano et al., 1994; Wang et al., 2004; Hibasami et al., 1998; Konoshima et al., 1991;Yang et al., 2002; Kong et al., 2005). It also has remarkable in vivo anti-tumor activities in tumor mouse models (Bai et al., 2003). Honokiol has demonstrated potent anti-angiogenic and anti-tumor properties against aggressive angiosarcoma by blocking of VEGF-induced VEGF receptor 2 autophosphorylation (Konoshima et al., 1991; Yang et al., 2002).

MDR

Honokiol has also been found to down-regulate the expression of P-glycoprotein at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line. The down-regulation of P-glycoprotein is accompanied with a partial recovery of the intracellular drug accumulation (Xu et al., 2006).

Prostate Cancer

In addition, it has been shown that prostate cancer cells that failed to respond to hormone withdrawal responded to honokiol-induced apoptosis. It was found to significantly induce death in cells surrounding primary and metastatic prostate cancers, the prostate stromal fibroblasts, marrow stromal cells, and bone marrow-associated endothelial cells. Honokiol is hence a promising nontoxic agent that could be used as an adjuvant with low-dose docetaxel for the treatment of hormone-refractory prostate cancer and its distant bone metastases (Shigemura et al., 2007).

Anti-metastatic

Honokiol inhibited the activity of MMP-9, which may be responsible, in part, for the inhibition of tumor cell invasiveness (Nagase et al., 2001).

Breast Cancer

The development of more targeted and low toxic drugs from traditional Chinese medicines for breast cancer are needed due to most of the anti-breast cancer drugs often being limited because of drug resistance and serious adverse reactions. Results have shown that honokiol inhibited the rate of breast cancer MDA-MB-231 cell growth (Nagalingam et al., 2012).

Synergistic Effects with Other Cancer Treatments

One of the most promising benefits of honokiol 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.

Chemotherapy

• A 2013 in vitro study published in the International Journal of Oncology showed that honokiol synergized chemotherapy drugs in Multi-drug-resistant breast cancer (Tian et al., 2013). A 2011 in vitro study published in PLoS One found that honokiol enhanced the apoptotic effects of the anti-cancer drug gemcitabine against pancreatic cancer (Arora et al., 2011).

• In vivo research published in Oncology Letters in 2011 found honokiol enhanced the action of cisplatin against colon cancer (Cheng et al., 2011).

• A 2010 in vitro study from the Journal of Biological Regulators and Homeostatic Agents showed that honokiol resensitized cancer cells to doxorubicin in Multi-drug-resistant uterine cancer (Angelini et al., 2010).

• A 2010 in vitro study published in Toxicology Mechanisms and Methods showed honokiol performed synergistically with the drug imatinib against human leukemia cells (Wang et al., 2010).

• 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 (Liu et al., 2008).

• 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 (Battle et al., 2005).

Radiation treatment

• 2012 in vitro research published in Molecular Cancer Therapeutics showed that honokiol was able to sensitize cancer cells to radiation treatments (Ponnurangam et al., 2012).

• 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 (He et al., 2011).

Inhibition of multi-drug resistance

Honokiol has been shown to interact with genes that are involved with mechanisms of drug efflux, thus reversing MDR in experimental models. The exact mechanisms of action in this regard are thought to be related to effects of blocking of NF-kB activity, but other mechanisms may also be involved (Xu et al., 2006).

References

Angelini A, Di Ilio C, Castellani ML, Conti P, Cuccurullo F. (2010). Modulation of Multi-drug 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. Journal of Biological Regulators & Homeostatic Agents, 24(2). 197-205.


Arora S, Bhardwaj A, Srivastava SK, et al. (2011). Honokiol arrests Cell-cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells. PLoS One, 6(6), e21573. doi: 10.1371/journal.pone.0021573.


Bai X, Cerimele F, Ushio-Fukai M, et al. (2003). Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J Biol Chem, 278: 35501–7.


Battle TE, Arbiser J, Frank DA. (2005). The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Blood, 106(2), 690-697.


Chen G, Izzo J, Demizu Y, et al. (2009). Different redox states in malignant and nonmalignant esophageal epithelial cells and differential cytotoxic responses to bile acid and honokiol. Antioxid. Redox Signal., 11(5):1083–1095


Cheng N, Xia T, Han Y, et al. (2001). Synergistic anti-tumor effects of liposomal honokiol combined with cisplatin in colon cancer models. Oncology Letters, 2(5), 957-962.


Eliaz I. (2013). Honokiol research review: A promising extract with multiple applications. Natural Medicine Journal., 5(7).


Fried LE, Arbiser JL. (2009). Honokiol, a multifunctional anti-angiogenic and anti-tumor agent. Antioxid. Redox Signal., 1(5):1139–1148. doi: 10.1089/ARS.2009.2440.


He Z, Subramaniam D, Ramalingam S, et al. (2011). Honokiol radiosensitizes colorectal cancer cells: enhanced activity in cells with mismatch repair defects. American Journal of Physiology: Gastrointest and Liver Physiology, 301(5):G929-937.


Hibasami H, Achiwa Y, Katsuzaki H, et al. (1998). Honokiol induces apoptosis in human lymphoid leukemia Molt 4B cells. Int J Mol Med, 2:671–3.


Hirano T, Gotoh M, Oka K. (1994). Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells. Life Sci, 55:1061–9.


Hou X, Yuan X, Zhang B, Wang S, Chen Q. (2013). Screening active anti-breast cancer compounds from Cortex Magnolia officinalis by 2D LC-MS. J Sep Sci, 36(4):706-12. doi: 10.1002/jssc.201200896.


Kong ZL, Tzeng SC, Liu YC. (2005). Cytotoxic neolignans: an SAR study. Bioorg Med Chem Lett, 15: 163–6.


Konoshima T, Kozuka M, Tokuda H, et al. (1991). Studies on inhibitors of skin tumor promotion. IX. Neolignans from Magnolia officinalis. J Nat Prod, 54: 816–22.


Liu Y, Chen L, He X, et al. (2010). Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma. International Journal of Gynecological Cancer, 18(4), 652-659.


Liu SH, Wang KB, Lan KH, et al. (2012). Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice. PLoS One, 7(8):e43711.


Munroe ME, Arbiser JL, Bishop GA. (2007). Honokiol, a natural plant product, inhibits inflammatory signals and alleviates inflammatory arthritis. J. Immunol., 179(2):753–763


Nagalingam A, Arbiser JL, Bonner MY, Saxena NK, Sharma D. (2012). Honokiol activates AMP-activated protein kinase in breast cancer cells via an LKB1-dependent pathway and inhibits breast carcinogenesis. Breast Cancer Research, 14:R35 doi:10.1186/bcr3128


Nagase H, Ikeda K, Sakai Y. (2001). Inhibitory Effect of Magnolol and Honokiol from Magnolia obovata on Human Fibrosarcoma HT-1080 Invasiveness in vitro. Planta Med, 67(8): 705-708. DOI: 10.1055/s-2001-18345


Ponnurangam S, Mammen JM, Ramalingam S, et al. (2012). Honokiol in combination with radiation targets notch signaling to inhibit colon cancer stem cells. Molecular Cancer Therapeutics, 11(4), 963-972. doi: 10.1371/journal.pone.0043711.


Shigemura K, Arbiser JL, Sun SY, et al. (2007). Honokiol, a natural plant product, inhibits the bone metastatic growth of human prostate cancer cells. Cancer, 109(7), 1279-1289.


Tian W, Deng Y, Li L, et al. (2013). Honokiol synergizes chemotherapy drugs in Multi-drug-resistant breast cancer cells via enhanced apoptosis and additional programmed necrotic death. International Journal of Oncology, 42(2), 721-732. doi: 10.3892/ijo.2012.1739.


Wang Y, Yang Z, Zhao X. (2010). Honokiol induces parapoptosis and apoptosis and exhibits schedule-dependent synergy in combination with imatinib in human leukemia cells. Toxicology Mechanisms and Methods, 20(5), 234-241. doi: 10.3109/15376511003758831.


Wang T, Chen F, Chen Z, et al. (2004). Honokiol induces apoptosis through p53-independent pathway in human colorectal cell line RKO. World J Gastroenterol, 10: 2205–8.


Wen J, Fu AF, Chen LJ, et al. (2009). Liposomal honokiol inhibits VEGF-D-induced lymphangiogenesis and metastasis in xenograft tumor model. International Journal of Cancer, 124(11), 2709-2718. doi: 10.1002/ijc.24244.


Xu D, Lu Q, Hu X. (2006). Down-regulation of P-glycoprotein expression in MDR breast cancer cell MCF-7/ADR by honokiol. Cancer Letters, 243(2), 274-280.


Yang SE, Hsieh MT, Tsai TH, Hsu SL. (2002). Down-modulation of Bcl-XL, release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells. Biochemical Pharmacology, 63(9), 1641-1651.

Source

Eliaz I. (2013). Honokiol research review: A promising extract with multiple applications. Natural Medicine Journal., 5(7). Retrieved from http://www.naturalmedicinejournal.com/article_content.asp?edition=1.