Plant Spotlight Series     

Turmeric and Ibrutinib - Side by Side Comparison   December 2019 (Series # A004)  

 

Turmeric  

● Produced from the rhizome of the plant Curcuma longa .  

● Turmeric identified ingredients are  

○ Polyphenols – The yellow-pigmented fraction of turmeric contains curcuminoids. The major                      

curcuminoids present in turmeric are demethoxycurcumin (curcumin II),                

bisdemethoxycurcumin (curcumin III), and cyclocurcumin.  

Ibrutinib  ● Oral Small molecule inhibitor of BTK (Bruton Tyrosine Kinase). BTK is a signaling molecule of the                                

B-cell antigen receptor (BCR) and cytokine receptor pathways. Other targets include BLK, BMX,                          

CSK, FGR, BRK, HCK, EGFR, YES, ERBB2, ITK etc.  

● Approved for the treatment of Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia/Small                      

Lymphocytic Lymphoma including those with 17p deletion, Waldenström’s Macroglobulinemia,                  

Marginal Zone Lymphoma and Chronic Graft versus Host Disease.    

 

addon.life     

 

Plant Spotlight Series : Turmeric and Ibrutinib- Side by Side Comparison    

 

  Turmeric (Curcumin)   Ibrutinib  

 

   

Marketed by   Generic, and available as a Dietary            Supplement  

J&J and AbbVie  

Biological Targets   Number of targets including Spleen          associated tyrosine kinase ( SYK), a          key signaling kinase downstream of          B-Cell Receptor ; SRC      proto-oncogene (SRC), a key        signaling kinase downstream of        different receptors ; Arachidonate      12-lipoxygenase (ALOX12), an      inflammatory kinase ; Survival      protein (BCL2), apoptosis inhibitor ;        Dual specificity tyrosine      phosphorylation regulated kinase 2        (DYRK2), kinase that phosphorylate        26-S proteasome ; E1A binding        protein p300 (EP300), histone        acetyltransferase ; Glyoxalase I      (GLO1), enzyme in glutathione        metabolism ; Inosine monophosphate      dehydrogenase (IMPDH), key      enzyme in purine metabolism ; Kelch          like ECH associated protein 1          (KEAP1), anti-oxidant regulator ;      Nuclear factor kappa B1 (NFKB1 ),          key transcription factor ( Gururajan        M et al, J Immunol., 2007 ; Leu TH et                  al, Biochem Pharmacol., 2003 ;        Jankun J et al, Mol Cancer Ther.,              2006 ; Luthra PM et al, Biochem            Biophys Res Commun., 2009 ;        Banerjee S et al, Proc Natl Acad Sci U                  S A., 2018 ; Simon RP et al, J Med                  Chem., 2016 ; Yuan M et al, Bioorg              

Number of targets including        Bruton tyrosine kinase (BTK),        B-Cell specific kinase; BLK        proto-oncogene ( BLK) , kinase      downstream of B-Cell receptor;        BMX non-receptor tyrosine kinase        (BMX); C-terminal Src kinase        (CSK) , important in T-Cell        activation; FGR proto-oncogene      ( FGR) , an SRC-family kinase;        Protein tyrosine kinase 6 (PTK6), a            kinase for oncogenic signaling;        HCK proto-oncogene (HCK), an        SRC-family kinase; Epidermal      growth factor receptor (EGFR),        oncogenic receptor tyrosine      kinase ; YES proto-oncogene 1        (YES1), an SRC-family kinase        ( Honigberg LA et al, Proc Natl Acad              

Sci U S A, 2010 )  

 

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Plant Spotlight Series : Turmeric and Ibrutinib- Side by Side Comparison    

Med Chem., 2011 ; Dairaku I et al,              Biosci Biotechnol Biochem., 2010 ;        Balogun E et al, Biochem J., 2003 ;              Bharti AC et al, Blood, 2003 )  

Pathways Targeted   B-Cell Receptor (BCR) Signaling,        NFKB Signaling, BCL2 Signaling,        Histone acetylation, Microtubule      Dynamics, MYC Signaling    

B-Cell Receptor (BCR) Signaling,        BCR dependent PI3K, PKC, NFKB          and other Signaling  

Clinical Dosing   In general 3600 mg Daily used in              clinical trials ( Kuriakose MA et al,            Cancer Prev Res (Phila)., 2016 )  

For MCL and MZL: 560 mg taken              orally once daily. For CLL/SLL,          WM, and cGVHD: 420 mg taken            orally once daily ( Ibrutinib        Prescribing information )   

Approved by FDA for   Not approved as a therapeutic agent   Mantle cell lymphoma (MCL) who          have received at least one prior            therapy; Chronic lymphocytic      leukemia (CLL)/Small lymphocytic      lymphoma (SLL); Chronic      lymphocytic leukemia (CLL)/Small      lymphocytic lymphoma (SLL) with        17p deletion; Waldenström’s      macroglobulinemia (WM);    Marginal zone lymphoma (MZL)        who require systemic therapy and          have received at least one prior            anti-CD20-based therapy; Chronic      graft versus host disease (cGVHD)          after failure of one or more lines of                systemic therapy  

Off-Label Use for   Hemorrhage, Diarrhea,    Beta-Thalassemia, Flatulence,    Abdominal Bloating, Loss Of        Appetite, Jaundice, Hepatitis,      Helicobacter Pylori (H Pylori), Peptic          Ulcers, Irritable Bowel Syndrome,        Liver And Gallbladder Conditions,        Headaches, Stress, Bronchitis,      Common Cold, Respiratory      Infections, Allergic Rhinitis (Hay        Fever), Asthma, Hyperlipidemia,      Lichen Planus, Oral Mucositis,        Radiation Dermatitis,    Chemotherapy-Induced Acral    Erythema, Fibromyalgia, Fatigue,      Leprosy, Fever, Amenorrhea,      Premenstrual Syndrome (PMS),      

Follicular lymphoma (FL), Diffuse        large B-cell lymphoma (DLBCL)  

 

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Plant Spotlight Series : Turmeric and Ibrutinib- Side by Side Comparison    

Radiation Proctopathy, Pruritus,      Exercise-Induced Muscle Soreness,      Postoperative Pain, Cancer Including        Colorectal Cancer And Prostate        Cancer, Depression, Age-Related      Cognitive Decline, Alzheimer's      Disease, Uveitis, Diabetes, Metabolic        Syndrome, Edema, Worms, Kidney        Inflammation, Systemic Lupus      Erythematosus (SLE), Tuberculosis,      Cystitis, Joint Pain  

Impact in CLL and MCL   CLL/MCL  

BCR/NFKB  Signaling  

BCL2  Signaling  

MYC  Signaling  

Inhibitor   Inhibitor   Inhibitor  

 

CLL/MCL  

BCR/NFKB  Signaling  

BCL2  Signaling  

MYC  Signaling  

Inhibitor   No effect   No effect  

 

Pros and Cons of Differential Impact  in CLL and MCL  

Pros   B-Cell malignancies are dependent        on B-Cell receptor (BCR) signaling.          BCR activate downstream signaling        via SYK/BTK/NFKB pathway.      Curcumin can inhibit SYK and          downstream signaling. Curcumin can        also inhibit BTK indirectly by          inhibiting EP300 ( Liu Z et al, J              Immunol., 2010 ).  In case of downstream mutations like            PLCG2, CARD11 etc., NFKB can be            constitutively activated independent      of BTK. Curcumin can also inhibit            NFKB independent of BTK.   Curcumin can also inhibit BCL2 and            MYC signaling which are key          biomarkers of CLL.   Cons  Poor bioavailability of curcumin may          limit its concentration towards        cancer cells. Low concentration may          not have significant effect on the            listed signaling.  

Pros   B-Cell malignancies are dependent        on B-Cell receptor (BCR) signaling.          BCR activate downstream      signaling via SYK/BTK/NFKB      pathway. Ibrutinib effectively      inhibits BTK and all the          downstream of BTK like NFKB,          PI3K-AKT and other pathway.   Cons  In case of downstream mutations          like PLCG2, CARD11 etc., NFKB          can be constitutively activated        independent of BTK. Ibrutinib        cannot inhibit those signaling        which are independent of BTK          ( Woyach JA et al, N Engl J Med.,                2014 ).  BCL2 and MYC can confer          resistance to Ibrutinib therapy        ( Lee J et al, Blood Adv., 2018 ; Deng                J et al, Leukemia., 2017 ; Sinha S et                al, Blood, 2018 ).  

Demonstrated Response   Stable disease in 28 out of 30 (93%)                stage 0-1 CLL/SLL patients. Used in            combination with Vitamin D. After a            median follow up of 29 months, EFS              

Overall Response rate (Partial and          complete response) ( Ibrutinib      Prescribing information )  Chronic Lymphocytic Leukemia /        

 

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Plant Spotlight Series : Turmeric and Ibrutinib- Side by Side Comparison    

was 72 percent, 74.1 percent had not              started new CLL treatment, and OS            was 100 percent ( curetoday ).  20% response in Rai stage 0/1            chronic lymphocytic leukemia (CLL)        patients (n=21) ( Golombick T et al,            Journal of Cancer Therapy, 2015 ).  A case report of unexpected long            survival of a CLL patient is published              taking curcumin with other dietary          supplements ( Haskin G et al, Integr            Med (Encinitas)., 2018 ).  Increased neutrophil count in 80%          (n=10) of MGUS/SMM patients with          curcumin- Ribraxx combination      ( Golombick T et al, Integr Cancer            Ther., 2016 ).  Curcumin showed comparable      efficacy (42% reduction in severity)          with Corticosteroids (49% reduction        in severity) when used topically for            Oral Graft-Versus-Host Disease      (n=26) ( Mansourian A et al, J Dent              (Tehran)., 2017 ).  

Small Lymphocytic Lymphoma –        43% for Ibrutinib (n=195) vs 4%            for Ofatumumab (n=196) in        RESONATE Trial ( Table 16 )  Chronic Lymphocytic Leukemia /        Small Lymphocytic Lymphoma –        82% for Ibrutinib (n=136) vs 35%            for Chlorambucil (n=133) in        RESONATE-2 Trial ( Table 18 )  Mantle Cell Lymphoma – 66% for            Ibrutinib (n=111) ( Table 15 )   Waldenström’s  Macroglobulinemia - 62% for        Ibrutinib (n=63) ( Table 20 )  Marginal Zone Lymphoma - 46%          for Ibrutinib (n=63) ( Table 21 )  Chronic Graft versus Host Disease          - 67% for Ibrutinib (n=42) ( Table            22 )  

Toxicity   Well tolerated. Some instances of          grade 1-2 Gastrointestinal toxicity        like constipation, dyspepsia,      diarrhea, distension,    gastroesophageal reflux, nausea,      vomiting etc are reported ( Carroll RE            wr al, Cancer Prev Res (Phila)., 2011 ).  

Anemia, Bruising, Cardiac      Arrhythmias, Diarrhea, Fatigue,      Hemorrhage, Muscle Spasms,      Musculoskeletal Pain, Nausea,      Neutropenia, Pneumonia, Pyrexia,      Rash, Second Primary      Malignancies, Stomatitis,    Thrombocytopenia( Ibrutinib  prescribing information )  

Available format and doses   Caplets, Capsules, Powder, Softgel        (1000 mg and others)  

Capsules: 70 mg and 140 mg;            Tablets: 140 mg, 280 mg, 420 mg,              and 560 mg  

Cost   $0.37/- (1x1000mg tablet)) ( amazon )   $150.15/- (1X140mg capsule)      ( Drugs.com )  

 

 

 

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Plant Spotlight Series : Turmeric and Ibrutinib- Side by Side Comparison    

Disclaimer  

● These statements have not been evaluated by the Food and Drug Administration. This analysis is                              

not intended to diagnose, treat, cure, or prevent any disease.  

● This website/document is provided for informational purposes only and is not intended as a                            

substitute for the advice provided by your physician or other healthcare professional.   

● You should not use the information on this website/document for diagnosing or treating a health                              

problem or disease, prescribing any medication or other treatment, or discontinuing any medication                          

or treatment recommended by your healthcare provider.  

 

 

   

 

December 2019 | Series #A004 addon.life 6