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Using Phytochemicals

Using Phytochemicals Synergistically with Chemotherapy to Improve Efficacy and Outcomes

 

The role of polyphenols in overcoming drug resistance. 

In a paper published in January 2022, Maleki Dana et al, engage in a thorough review of multiple polyphenols which, when used concurrently with chemotherapy, can inhibit the development of chemo-resistance, rendering treatment more effective and for a longer duration of time.    

Most oncologists are wary of negative drug-herb, drug nutrient interactions. 

 

polyphenols-fruits

This review shows that we can use polyphenol phytochemicals synergistically with chemotherapy treatments to support efficacy and outcomes.

 

The Outsmart Cancer® System is an Integrative Cancer Care model seeking to develop highly individualized care plans that include the best therapeutic approaches and tools from multiple disciplines, combining a disease focused targeted pathology model with a whole biosystem health model to support the best outcomes for patients.

 

Acquired drug resistance has become a challenge that may result in treatment failure.  Multiple factors contribute to chemo-resistance in cancer cells. Acquired drug resistance occurs when cancer cells fail to respond to a previously effective treatment.  Intrinsic  chemo-resistance occurs when a pre-existing factor causes a drug to be inefficient or ineffective.

 

Due to the inherent heterogeneity of tumors, subpopulations of cells may develop resistance while other subpopulations remain sensitive to treatment.  

This is the rationale for using multiple agents which impact multiple signally pathways and receptors to target a wide array of heterogeneous cells.  This is also the rationale for using multiple nutriceuticals, botanicals and phytochemicals concurrently to address multiple signaling pathways and functions.

In this excellent review paper the author focuses on the multiple synergistic functions of polyphenols citing multiple studies.

 

Polyphenols from medicinal plants and food plants form a large part of our Materia Medica. Polyphenols include several subclasses such as catechins, flavonoids, flavones, flavonols, anthocyanins, isoflavones, curcuminoids, chalcones and phenolic acids. These natural compounds are widely found found in deeply pigmented fruits, vegetables, cocoa, seeds and green and black teas,

 

Not only do polyphenols inhibit multiple pathways and mechanisms of drug resistance, but also act to  confront many of the Hallmarks of Cancer, thus inhibiting and controlling the activity and viability of malignant cells.

 

The multiple functional roles of

  • Resveratrol
  • EGCG Epigallocatechin gallate
  • Curcumin 

are discussed and examined in depth examining multiple pathways, mechanisms of action and dosing.

Also discussed are additional well researched polyphenols, many of which are sourced from food plants as well as medicinal plants including

  • Quercetin 
  • Baicalin
  • Baicalien
  • Apigenin
  • Chrysin
  • Luteolin
  • Kaempferol

Mechanisms which lead to drug resistance in tumor cells

Malignant cells are highly adaptive and respond to toxic stressors such as chemotherapeutic drugs in the tumor micro-environment in service to their own survival.  Essential malignant cells are “smart” and they can not only co-opt normal physiologic and metabolic functions within cells to respond to the presence of toxic drug therapies.

  • Decreased Drug Uptake by tumor cells
  • Drug Efflux from tumor cells (membrane pumps)
  • Alterations in drug metabolism
  • Epigenetic Modification and Signaling
  • Inhibition of Programmed Cell death via apoptosis, autophagy and necrosis in tumor cells
  • Alterations in DNA repair 
  • Activity of Cancer Stem Cells
  • Redox Capacity of cells in response to oxidative stress
  • Alterations in Epithelial to Mesenchymal Transition, Invasion and Metastatic Progression

Not only are polyphenols capable of addressing the common Hallmarks of Cancer, but they can also inhibit the multiple ways that malignant cells seek to survive in the face of drug therapies.  

 

Therefore, we should strategically combine chemo-therapeutic  agents with selected polyphenols to both enhance therapeutic effect as well as inhibit the development of drug resistance. 

 

This leads to greater therapeutic benefit, increased duration of action as well as skillful management of adverse effects.

I encourage you to read this paper in detail for a deep and detailed review of the mechanisms of these pleomorphic multitaskers polyphenols.  The polyphenols mentioned in this paper have a history of wide use and safety.

 

Our role is to both eradicate and inhibit neoplastic cells as well as nurture and support the health of the patient.  This is at the heart of the OutSmart Cancer® System.

 

References

 

The Role of Polyphenols in Overcoming Cancer Drug Resistance: A Comprehensive Review 

Maleki Dana et al

Cellular and Molecular Biology Letters (2022) 27:1

https://doi.org/10.1186/s11658-021-00301-9

 

Hallmarks of Cancer: The Next Generation

Douglas Hanahan, Robert A. Weinberg, 2011

https://doi.org/10.1016/j.cell.2011.02.013

 

Revisiting the hallmarks of cancer

Fouad YA, Aanei C.. Am J Cancer Res. 2017 May 1;7(5):1016-1036. PMID: 28560055; PMCID: PMC5446472.

 

Oral Cancer AIIORE Blog

Phytochemicals in Oral Cancer Prevention and Therapy

Oral cancers originate in the oral cavity and may spread to the neck and throat and local lymph nodes and can metastasize. These cancers are most commonly squamous cell carcinomas and are often very aggressive.

Cancers of the oral cavity, head, and neck are linked to drinking alcohol, smoking tobacco, betel nut chewing, human papillomavirus infection, and nutritional deficiencies.

Phytochemicals are a useful adjunct therapy for both prevention and therapy.

The continuous increase in cancer cases, the failure of conventional chemotherapies, and the excessive toxicity of chemotherapies demand alternative cancer treatments.

Phytochemicals can inhibit or antagonize factors, which are dysregulated in cancer cells and may enhance the effects of conventional therapy or could be developed into a stand-alone therapy*

Phytochemicals may exert their chemopreventive properties by blocking the critical events of tumor initiation and promotion, thereby reversing the premalignant stage. Phytochemicals may also prevent tumorigenesis by inhibiting or slowing tumor progression or promoting cell differentiation. Furthermore, phytochemicals can enhance innate immune surveillance and improve the elimination of transformed cells.”**

Phytochemicals that impact multiple pathways active in the development, growth, progression, and spread of oral cancers include

Phytochemicals in Oral Cancer
  • Black Raspberry anthocyanins
  • Green Tea Catechins (EGCG, EGC, ECG)
  • Curcuma longa (curcuminoids) (tumeric)
  • Alliums: Garlic and Onions (allicin, s-allylcysteine)
  • Resveratrol 3,4’,5-trihydroxy-trans-stilbene
  • Lycopene carotenoid (tomatoes, red bell peppers)
  • Astaxaxanthin and Canthaxanthin  carotenoid xanthophylls  (green leafy vegetables)
  • Bromelain cysteine protease (pineapple)

For a detailed and thorough discussion of risk factors, etiologies, signs and symptoms, histopathology, molecular mechanisms and therapeutic interventions in oral, head, and neck cancers see: 

*Tzu-Ying Lee , Yu-Hsin Tseng Review : Biomolecules  The Potential of Phytochemicals in Oral Cancer Prevention and Therapy: A Review of the Evidence 2020 Aug 6;10(8):1150. doi: 10.3390/biom10081150

** Kotecha R., Takami A., Espinoza J.L. Dietary phytochemicals and cancer chemoprevention: A review of the clinical evidence. Oncotarget. 2016;7:52517–52529. doi: 10.18632/oncotarget.9593.


 

chemotherapy

Brain Cancer: Resolving Cancer Related Cognitive Impairment

Did you know that 45% of all cancer patients self-report a decline in cognitive function after completing chemotherapy?

Brain Cancer-related cognitive impairment is attributed to both cancer as well as treatment-related changes in cytokine profiles, blood brain barrier permeability, genetic susceptibility, hormonal factors and mitochondrial dysfunction.

Both the disease itself and the treatments, can impact attention, memory and executive functions, as well, as brain structure and anatomy.

As many as 20% of all patients report continued persistent changes in cognitive function as many as 10-20 years after completing successful treatment.

Eight Nutraceuticals and Phytochemicals that Promote Neuron Repair and Support Restoration of the Blood Brain Barrier and Cognitive Function

 

Brain Cancer


1. Melatonin (10-20mg hs) -
Maintains Blood Brain Barrier Integrity and Permeability

  • Inhibits Matrix Metalloproteinase-9 (MMP-9)
  • Inhibits NADPH oxidase-2
  • Activates SIRT1 Silent Information Regulator 1
  • Activates AMP Activated Protein Kinase (AMPK)

2. Astragalus (1-6g/day) - Decreases Blood Brain Barrier Permeability

  • Inhibition of MMP-9 Neuro-Immuno-regulation
  • Control of Oxidative Stress
  • Control of Neuro-inflammation
  • Regulation of Neuro-apoptosis
  • Inhibition of p53 Modulation of the Bcl-2/Bax

3. Resveratrol (1000mg bid x 52 weeks) - Regulates Neuro-Inflammation

  • Decreases CSF MMP9
  • Modulates neuro-inflammation
  • Induces adaptive immunity
  • Activates SIRT1

4. Pterobstilbene (50-100mg/d) - Attenuates Learning and Memory Impairment

  • Inhibitory effect on microglia activation
  • Protective effect on neuronal injury
  • Decreases production of NO, TNF-α and IL-6 in microglial cells
  • More lipophilic than Resveratrol

5. Unique Probiotic Blend (KLAIRE Target gb-X 1 packet/day) - Targets Gut-Brain Axis

  • Strengthening of the gut barrier function
  • Modulation of cytokines and inflammatory response
  • Production of potentially neuroprotective metabolites
  • Shift away from macrophage-produced cytokines to T-lymphocyte-produced cytokines
  • Reduction in circulating lipopolysaccharide endotoxins
  • Marked reduction in transcription of hippocampal genes related to HPA regulation

6. Curcumin (3-6g/day) - Improves Cognitive Function

  • Crosses Blood Brain Barrier
  • Supports Axonal Regeneration
  • Increases Brain Derived Neurotrophic Factor
  • Reduces NeuroInflammation linked to mood dysregulation and cognitive function
  • Stimulates Clearance of beta amyloid plaques

7. Omega-3 Fatty Acids (1.8g/d) - Protects Neurons From Toxic Effects of Chemotherapy

  • Opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis
  • A diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress

8. Lion's Mane Mushroom (3-5g/d) - Enhances Cognition

  • Strengthens Memory and Concentration
  • Stimulates the synthesis of Nerve Growth Factor Promotes and Accelerate Myelination
  • Immune Modulation