Category Archives: Antibiotic

anti-apoptotic, anti-inflammatory, Antibiotic, apoptosis, Apoptotic, Chapter 8 Injectables and Cancer Research, cytotoxic, Fibrosarcoma, Leukemia, neuro-protective, Pro-apoptotic, Sarcoma

Qingkailing

Cancer: Leukemia, sarcoma

Action: Antibiotic, anti-apoptotic, anti-inflammatory, neuro-protective, pro-apoptotic, immunomodulating, MMPs regulation

Anti-inflammatory and Immunomodulating

Qingkailing and Shuanghuanglian (SHHL) are two commonly used Chinese herbal preparations with reported anti-inflammatory activity. The effects of these two preparations on the capacity of staphylococcal toxic shock syndrome toxin 1 (TSST-1), to stimulate the production of cytokines (IL-1β, IL-6, TNF-α, IFN-γ) and chemokines (MIP-1α, MIP-1β and MCP-1) by peripheral blood mononuclear cell (PBMC), was tested. Their effect on LPS-stimulated NF-κB transcriptional activity in a THP-1 cell line, and on human monocyte chemotactic response to chemoattractants, was also evaluated.

The results suggested that the pharmacological basis for the anti-inflammatory effects of Qingkailing and SHHL is the result of suppression of NF-κB regulated gene transcription, leading to suppressed production of pro-inflammatory cytokines and chemokines. Interference with leukocyte chemotaxis also contributes to the anti-inflammatory and immunomodulating effects of these medicinals. Identification of the responsible components in these two herbal preparations may yield compounds suitable for structural modification into potent novel drugs (Chen et al., 2002).

Leukemia

The MTT assay, cell morphology, DNA gel electrophoresis, and flow-cytometry were utilized to study the apoptotic effect of Qingkailing, and its active compounds, on the human acute promyelocytic leukemia (HL-60) cell line.

Qingkailing and its active compounds, Baicalin and hyodeoxycholic acid, exhibited strong cytotoxicity in inhibiting HL-60 cells, while Bezoar cholic acid showed a weaker effect. Apoptosis could be induced after being treated for 6 h by the former two compounds, displaying a typical apoptosis peak under flow-cytometry, but could not be induced by the latter.

Qingkailing could induce apoptosis in leukemia cells in vitro, which could serve as a mechanism of Qingkailing in the treatment of acute promyelocytic leukemia (Chen, Dong, & Zhang, 2001).

Qingkailing injection could prevent the decrease of MMP induced by injury of hypoxia-hypoglycemia-reoxygenation, stabilize MMP, inhibit cell apoptosis, and protect hippocampal neurons (Tsing, 2006).

Matrix Metalloproteinases (MMPs) Regulation

Matrix metalloproteinases (MMPs) play vital roles in many pathological conditions, including cancer, cardiovascular disease, arthritis and inflammation. Modulating MMP activity may therefore be a useful therapeutic approach in treating these diseases. Qingkailing is a popular Chinese anti-inflammatory formulation used to treat symptoms such as rheumatoid arthritis, acute hypertensive cerebral hemorrhage, hepatitis and upper respiratory tract infection.

One of the components of Qingkailing, Fructus gardeniae, strongly inhibits MMP activity. The IC50 values for the primary herbal extract and water extract against MMP-16 were 32 and 27 µg/ml, respectively. In addition, the herbal extracts influenced HT1080 human fibrosarcoma cell growth and morphology.

These data may provide molecular mechanisms for the therapeutic effects of Qingkailing and herbal medicinal Fructus gardenia (Yang et al., 2008).

Sources

Chen X, Howard OM, Yang X, Wang L, Oppenheim JJ, Krakauer T. (2002). Effects of Shuanghuanglian and Qingkailing, two multi-components of traditional Chinese medicinal preparations, on human leukocyte function. Life Sciences, 70(24), 2897-2913.


Chen ZT, Dong Q, Zhang L. (2001). Study on the effect of Qingkailing injection and its active principle in inducing cell apoptosis in human acute promyelocytic leukemia. Chinese Journal of Integrated Traditional and Western Medicine, 21(11), 840-842.


Tsing H. (2006). Influences of Qingkailing Injection on neuron apoptosis and mitochondrial membrane potential. Journal of Beijing University of Traditional Chinese Medicine, 2006(2), R285.5.


Yang JG, Shen YH, Hong Y, Jin FH, Zhao SH, Wang MC, Shi XJ,   Fang XX. (2008). Stir-baked Fructus gardeniae (L.) extracts inhibit matrix metalloproteinases and alter cell morphology. Journal of Ethnopharmacology, 117(2), 285-289.

anti-apoptotic, anti-inflammatory, Antibiotic, apoptosis, Apoptotic, cardiovascular disease, Chapter 7 Isolates and Cancer Research, Fibrosarcoma, IL-1, IL-6, immunomodulating, inflammation, MCP-1, MMPs regulation, neuro-protective, Pro-apoptotic, Sarcoma, TNF

Qingkailing

Cancer: Leukemia, sarcoma

Action: Antibiotic, anti-apoptotic, anti-inflammatory, neuro-protective, pro-apoptotic, immunomodulating, MMPs regulation

Anti-inflammatory and Immunomodulating

Qingkailing and Shuanghuanglian (SHHL) are two commonly used Chinese herbal preparations with reported anti-inflammatory activity. The effects of these two preparations on the capacity of staphylococcal toxic shock syndrome toxin 1 (TSST-1), to stimulate the production of cytokines (IL-1β, IL-6, TNF-α, IFN-γ) and chemokines (MIP-1α, MIP-1β and MCP-1) by peripheral blood mononuclear cell (PBMC), was tested. Their effect on LPS-stimulated NF-κB transcriptional activity in a THP-1 cell line, and on human monocyte chemotactic response to chemoattractants, was also evaluated.

The results suggested that the pharmacological basis for the anti-inflammatory effects of Qingkailing and SHHL is the result of suppression of NF-κB regulated gene transcription, leading to suppressed production of pro-inflammatory cytokines and chemokines. Interference with leukocyte chemotaxis also contributes to the anti-inflammatory and immunomodulating effects of these medicinals. Identification of the responsible components in these two herbal preparations may yield compounds suitable for structural modification into potent novel drugs (Chen et al., 2002).

Leukemia

The MTT assay, cell morphology, DNA gel electrophoresis, and flow-cytometry were utilized to study the apoptotic effect of Qingkailing, and its active compounds, on the human acute promyelocytic leukemia (HL-60) cell line.

Qingkailing and its active compounds, Baicalin and hyodeoxycholic acid, exhibited strong cytotoxicity in inhibiting HL-60 cells, while Bezoar cholic acid showed a weaker effect. Apoptosis could be induced after being treated for 6 h by the former two compounds, displaying a typical apoptosis peak under flow-cytometry, but could not be induced by the latter.

Qingkailing could induce apoptosis in leukemia cells in vitro, which could serve as a mechanism of Qingkailing in the treatment of acute promyelocytic leukemia (Chen, Dong, & Zhang, 2001).

Qingkailing injection could prevent the decrease of MMP induced by injury of hypoxia-hypoglycemia-reoxygenation, stabilize MMP, inhibit cell apoptosis, and protect hippocampal neurons (Tsing, 2006).

Matrix Metalloproteinases (MMPs) Regulation

Matrix metalloproteinases (MMPs) play vital roles in many pathological conditions, including cancer, cardiovascular disease, arthritis and inflammation. Modulating MMP activity may therefore be a useful therapeutic approach in treating these diseases. Qingkailing is a popular Chinese anti-inflammatory formulation used to treat symptoms such as rheumatoid arthritis, acute hypertensive cerebral hemorrhage, hepatitis and upper respiratory tract infection.

One of the components of Qingkailing, Fructus gardeniae, strongly inhibits MMP activity. The IC50 values for the primary herbal extract and water extract against MMP-16 were 32 and 27 µg/ml, respectively. In addition, the herbal extracts influenced HT1080 human fibrosarcoma cell growth and morphology.

These data may provide molecular mechanisms for the therapeutic effects of Qingkailing and herbal medicinal Fructus gardenia (Yang et al., 2008).

Sources

Chen X, Howard OM, Yang X, Wang L, Oppenheim JJ, Krakauer T. (2002). Effects of Shuanghuanglian and Qingkailing, two multi-components of traditional Chinese medicinal preparations, on human leukocyte function. Life Sciences, 70(24), 2897-2913.


Chen ZT, Dong Q, Zhang L. (2001). Study on the effect of Qingkailing injection and its active principle in inducing cell apoptosis in human acute promyelocytic leukemia. Chinese Journal of Integrated Traditional and Western Medicine, 21(11), 840-842.


Tsing H. (2006). Influences of Qingkailing Injection on neuron apoptosis and mitochondrial membrane potential. Journal of Beijing University of Traditional Chinese Medicine, 2006(2), R285.5.


Yang JG, Shen YH, Hong Y, Jin FH, Zhao SH, Wang MC, Shi XJ,   Fang XX. (2008). Stir-baked Fructus gardeniae (L.) extracts inhibit matrix metalloproteinases and alter cell morphology. Journal of Ethnopharmacology, 117(2), 285-289.

A549, Anti-cancer, anti-inflammatory, anti-oxidant, anti-proliferative, anti-proliferative effect, anti-tumor, Antibiotic, BAX, Bcl-2, Chapter 7 Isolates and Cancer Research, Chemo-protective, Colon Cancer or Colorectal cancer, CSK, Dox-induced cardiotoxicity, Doxorubicin-induced cardotoxicity, Eca-109, Esophageal cancer, Hippophae rhamnoides, HL-60, HT-29, K562, Lung cancer, Lymphoma, Rectal cancer, YAC-1

Isorhamnetin

Cancer:
Lung, colon, acute myeloid leukemia, T lymphoma, Ehrlich carcinoma, gastric, esophageal squamous cell, chronic myelogenous leukemia

Action: Dox-induced cardiotoxicity, anti-oxidant

Isorhamnetin, the anti-tumor component of Hippophae rhamnoides Linn, is also a member of the ßavonoid class of compounds. Its chemical name is 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl) chromen-4-one and its molecular formula is C16H12O7.

Lung Cancer

Isorhamnetin shows good inhibitory effects on human lung adenocarcinoma A549 cells, human colon cancer HT-29 cells, human chronic myeloid leukemia K562 cells, human acute myeloid leukemia HL-60 cells, mouse T lymphoma YAC-1 cells and mouse Ehrlich carcinoma. In terms of its mechanism of action, it seems that isorhamnetin simultaneously reduces the expression of Bcl-2 and increases the expression of Bax, which activates caspase-9 and its downstream factor caspase-3, thus resulting in cell death (Zhu et al. 2005).

Colorectal Cancer

It was demonstrated that isorhamnetin prevents colorectal tumorigenesis. Dietary isorhamnetin decreased mortality, tumor number, and tumor burden by 62%, 35%, and 59%, respectively. Magnetic resonance imaging, histopathology, and immunohistochemical analysis revealed that dietary isorhamnetin resolved the DSS-induced inflammatory response faster than control diet.

These observations suggest the chemo-protective effects of isorhamnetin in colon cancer are linked to its anti-inflammatory activities and its inhibition of oncogenic Src activity and consequential loss of nuclear β-catenin, activities that are dependent on CSK expression (Saud et al., 2013).

Gastric Cancer

The potential effects of isorhamnetin (IH), a 3'-O-methylated metabolite of quercetin, were investigated on the peroxisome proliferator-activated receptor γ (PPAR-γ) signaling cascade using proteomics technology platform, gastric cancer (GC) cell lines, and xenograft mice model.

It was observed that IH exerted a strong anti-proliferative effect and increased cytotoxicity in combination with chemotherapeutic drugs. IH also inhibited the migratory/invasive properties of gastric cancer cells, which could be reversed in the presence of PPAR-γ inhibitor.

Using molecular docking analysis, Ramachandran et al. (2013) demonstratd that IH formed interactions with seven polar residues and six nonpolar residues within the ligand-binding pocket of PPAR-γ that are reported to be critical for its activity and could competitively bind to PPAR-γ. IH significantly increased the expression of PPAR-γ in tumor tissues obtained from xenograft model of GC. Overall, these findings clearly indicate that anti-tumor effects of IH may be mediated through modulation of the PPAR-γ activation pathway in GC.

Cardiac-protective; Doxorubicin

Isorhamnetin is a natural anti-oxidant with obvious cardiac-protective effect. Its action against doxorubicin-induced cardotoxicity and underlying mechanisms were investigated. Doxorubicin (Dox) is an anthracycline antibiotic for cancer therapy with limited usage due to cardiotoxicity. The aim of this study is to investigate the possible protective effect of isorhamnetin against Dox-induced cardiotoxicity and its underlying mechanisms. In an in vivo investigation, rats were intraperitoneally (i.p.) administered with Dox to duplicate the model of Dox-induced chronic cardiotoxicity.

Daily pre-treatment with isorhamnetin (5 mg/kg, i.p.) for 7 days was found to reduce Dox-induced myocardial damage significantly, including the decline of cardiac index, decrease in the release of serum cardiac enzymes, and amelioration of heart vacuolation. In vitro studies on H9c2 cardiomyocytes, isorhamnetin was effective to reduce Dox-induced cell toxicity. Isorhamnetin also potentiated the anti-cancer activity of Dox in MCF-7, HepG2 and Hep2 cells. These findings indicated that isorhamnetin can be used as an adjuvant therapy for the long-term clinical use of Dox (Sun et al., 2013).

Chronic Myelogenous Leukemia

The isorhamnetin 3-o-robinobioside and its original extract, ethyl acetate extract, from Nitraria retusa leaves, were evaluated for their ability to induce anti-oxidant and anti-genotoxic effects in human chronic myelogenous leukemia cell line. They were shown to have a great anti-oxidant and anti-genotoxic potential on human chronic myelogenous leukemia cell line K562 (Boubaker et al., 2012).

Esophageal Cancer

The flavonol aglycone isorhamnetin shows anti-proliferative activity in a variety of cancer cells and it inhibits the proliferation of human esophageal squamous carcinoma Eca-109 cells in vitro (Shi et al., 2012).

Cancer:
Actions: Overcomes MDR; P-glycoproteins, breast cancer resistance proteins (BCRP), efflux transporters

Flavonoid isorhamnetin occurs in various plants and herbs, and demonstrates various biological effects in humans. This work will clarify the isorhamnetin absorption mechanism using the Caco-2 monolayer cell model. The isorhamnetin transport characteristics at different concentrations, pHs, temperatures, tight junctions and potential transporters were systemically investigated.

Isorhamnetin was poorly absorbed by both passive diffusion and active transport mechanisms. Both trans- and paracellular pathways were involved during isorhamnetin transport. Active transport under an ATP-dependent transport mechanism was mediated by the organic anion transporting peptide (OATP); isorhamnetin’s permeability from the apical to the basolateral side significantly decreased after estrone-3-sulfate was added (p<0.01).

Efflux transporters, P-glycoproteins (P-gp), breast cancer resistance proteins (BCRP) and multidrug resistance proteins (MRPs) participated in the isorhamnetin transport process. Among them, the MRPs (especially MRP2) were the main efflux transporters for isorhamnetin; transport from the apical to the basolateral side increased 10.8-fold after adding an MRP inhibitor (MK571).

References

Boubaker J, Ben Sghaier M, Skandrani I, et al. (2012). Isorhamnetin 3-O-robinobioside from Nitraria retusa leaves enhance anti-oxidant and anti-genotoxic activity in human chronic myelogenous leukemia cell line K562. BMC Complement Altern Med, 12:135. doi: 10.1186/1472-6882-12-135.


Ramachandran L, Manu KA, Shanmugam MK, et al. (2013). Isorhamnetin inhibits proliferation and invasion and induces apoptosis through the modulation of peroxisome proliferator-activated receptor γ activation pathway in gastric cancer. J Biol Chem, 288(26):18777. doi: 10.1074/jbc.A112.388702.


Saud SM, Young MR, Jones-Hall YL, et al. (2013). Chemo-preventive activity of plant flavonoid isorhamnetin in colorectal cancer is mediated by oncogenic Src and β -catenin. Cancer Res, 73:5473.


Shi C, Fan LY, Cai Z, Liu YY, Yang CL. (2012). Cellular stress response in Eca-109 cells inhibits apoptosis during early exposure to isorhamnetin. Neoplasma, 59(4):361-9. doi: 10.4149/neo_2012_047.


Sun J, Sun G, Meng X, et al. (2013). Isorhamnetin protects against doxorubicin-induced cardiotoxicity in vivo and in vitro. PLoS One, 8(5):e64526. doi: 10.1371/journal.pone.0064526.


Zhu L, Wang ZR, Zhou LM, et al. (2005). Effects and mechanisms of isorhamnetin on lung carcinoma. Space Med Med Eng (Chin), 18:381-383.


Duan J, Xie Y, Luo H, Li G, Wu T, Zhang T. (2014) Transport characteristics of isorhamnetin across intestinal Caco-2 cell monolayers and the effects of transporters on it. Food Chem Toxicol. 2014 Apr;66:313-20. doi: 10.1016/j.fct.2014.02.003.

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.