CHEMOTHERAPY POTENTIATING AGENTS
by Bradford S. Weeks, M.D.
If you decide to take chemotherapy, the principles of Corrective Cancer Care suggest that you should discuss with your oncologist the opportunity to potentiate the chemotherapy agent so as kill cancer more efficiently while minimizing side-effects. What follows is a brief summary of agents which merit consideration.
- Insulin
- Fasting
- Metformin
- Curcumin
- Sulforafane
- Fermented Soy
- Aspirin
- Vitamin C
- Dipyridamole (inhibitor of nucleoside transport)
INSULIN
Physiologic Effects After IV Insulin:
Membrane Effect
Improved drug penetration into cancer cells
Use lower doses to reduce side effects
Shorten treatment cycle intervals
Metabolic Effect
Increased proportion in S phase.
Increase rate of cell kill per cycle
Cellular Differentiation Effect
Excess IR & IGF-R on cancer cells
Specifically targets cancer “smart bomb”
Relative sparing of normal tissue from toxicity
In vitro, after adding insulin to an asynchronous population of breast cancer cells, the S phase fraction was 66% compared to only 37% in the controls.
IPT is a chemotherapy-based protocol using insulin as a biologic response modifier of the endogenous mechanisms of malignancy.
In IPT, insulin is used to selectively target cancer cells with lowered doses of chemotherapy drugs, enhancing drug effects on these cells and, at the same time, effectively reducing dose-related chemotherapy side effects on host normal tissue
Summary: Biochemistry of Insulin and Cancer
- Glucose is the ONLY fuel cancer cells can use
- Cancer cells have 6 to 17x > IRs than regular cells
- Cancer cells have 10 x > IGF-1 Rs than regular cells
- INS+IR increases delta-9-desaturase which makes cancer cells become permeable
- Insulin doubles number of cancer cells in S-phase; increasing vulnerability to chemotherapy drugs
- In the presence of insulin, cancer cells are selectively targeted so lower doses of chemo drugs preserves immune function
- Appetite improves, weight and euphoria increase
FASTING
“Fasting can actually make cancerous cells more susceptible to chemotherapy”
Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy.
Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8215-20. Epub 2008 Mar 31.
Raffaghello L, Lee C, Safdie FM, Wei M, Madia F, Bianchi G, Longo VD
METFORMIN
Metformin selectively kills the chemotherapy resistant cancer STEM cells
Cancer Res. 2011 May 1;71(9):3196-201. Epub 2011 Mar 17. Iliopoulos D, Hirsch HA, Struhl K
Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.
Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancer STEM cells (CSC) in genetically distinct types of breast cancer cell lines.
In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse.
Metformin and cancer: new applications for an old drug.
Kourelis TV, Siegel R Med Oncol. 2011 Feb 8.
Metformin, one of most widely prescribed oral hypoglycemic
agents, has recently received increased attention because of its
potential antitumorigenic effects that are thought to be
independent of its hypoglycemic effects. Several potential
mechanisms have been suggested for the ability of metformin to
suppress cancer growth in vitro and vivo: (1) activation of
LKB1/AMPK pathway, (2) induction of cell cycle arrest and/or
apoptosis, (3) inhibition of protein synthesis, (4) reduction in
circulating insulin levels, (5) inhibition of the unfolded protein
response (UPR), (6) activation of the immune system, and
(7) eradication of cancer stem cells.
Metformin: A Diabetes Drug for Cancer or a Cancer Drug for Diabetics?
Martin M Marais, M J Clin Oncology. Vol 30 No 21 July 20th 2012
Metformin and reduced risk of Cancer in Diabetic Patients. Evans JM BJM
330:1304-1305, 2005
Long-term Metformin use is associated with decreased risk of Breast Cancer.
Bodmer M, Meier C. Diabetes Care 33:1304-1308 2010
CURCUMIN
Curcumin, the yellow pigment found in the spice turmeric and a key ingredient in yellow curry inhibits melanoma cell growth and stimulates tumor cell death via apoptosis
“potent antioxidant, anti-inflammatory and cancer terminating effects…”
Cancer August 15, 2005
Pre-Clinical evidence for curcumin and various cancers Anand et al Cancer Letters 2008
Curcumin potentiates Gemcitabine-Induced apoptosis in human pancreatic cancer cells Kunnumakkara AB 2007
Curcumin potentiates the effect of chemotherapy Goel at al Nutrition and Cancer 2010
SULFORAPHANE
Sulforaphane (broccoli) enhances chemotherapy
Sulforaphane protects against cisplatin-induced nephrotoxicity.
Guerrero-Beltrán CECalderón-Oliver MTapia E Pedraza-Chaverri J. et al Toxicol Lett. 2010 Feb 15;192(3):278-85. Epub 2009 Nov 12.
Sulforaphane (SFN) attenuated CDDP-induced renal dysfunction, structural damage, oxidative/nitrosative stress, glutathione depletion, enhanced urinary hydrogen peroxide excretion and the decrease in antioxidant enzymes (catalase, glutathione peroxidase and glutathione-S-transferase).
The renoprotective effect of SFN on CDDP-induced nephrotoxicity was associated with the attenuation in oxidative/nitrosative stress and the preservation of antioxidant enzymes.
FERMENTED SOY
This raw, fermented, organic, non-GMO, whole soy product contains all 5 of the super foods discovered in 1991 by the National Cancer institute after the
$20 million study searching for anti-cancer properties in fruits and vegetables:
1) Isoflavones
2) Protease Inhibitors
3) Saponins
4) Phytosterols
5) Phytic Acid Compounds
ASPIRIN
ӻAspirin can help reduce Cancer spread
weeksmd.com/2012/02/aspirin-can-help-reduce-cancer-spread/
If you have been reading my posts about addressing cancer STEM cells which are recruited to a tumor by interleukin 8 (an inflammatory cytokine) then this new article about the benefits of aspirin (an anti-inflammatory agent) will not surprise you! Why hasn’t your oncologist told you about this cheap and safe (when not used to excess) medicine?
Aspirin – safe and effective in cancer care
https://weeksmd.com/2012/04/aspirin-safe-and-effective-in-cancer-care/
Aspirin, a potent anti-inflammatory agent is one of many agents shown to “doctor” the cancer STEM cells which reduces metastatic disease. We shared this news with our readers a couple of months ago. Fermented soy, extracts of fish oil, Metformin (berberine) and many other agents help too. Learn more about this topic by reviewing my recent lecture on “doctoring the cancer STEM cell “Evidence from 3 new studies demonstrates that aspirin can reduce the risk for cancer-related mortality and can reduce or prevent the risk for distant metastasis.”
VITAMIN C
Vitamin C plus Vitamin K3
1. Vitamin K3 alone has demonstrated anti-tumor activity against multiple rodent and human cancer cell lines.
2. Synergism noted with doxorubicin, 5 FU, vinblastine, vincristine, mitomycin, bleomycin, cisplatin, mitoxanthrone, MTX, and many others.
3. Phase I trials in humans 400-500 mg/day showed no toxicity in combination with mitomycin. Phase II trials of IV K3 (2.5 gms/m2) with mitomycin showed objective response but 30% showed hemolysis (Gold, Cancer Treat Rep, 1986)
Vit C and K3 combination showed synergistic activity in a 100/1 ratio in breast, endometrial and oral epidermoid carcinoma cell lines in concentrations 10-50 times lower than for the individual vitamins (Noto, et al, Cancer, 1989).
2) Co administration of C plus K3 with adriamycin, bleomycin, mitomycin C, vincristine or cisplatin increased growth inhibitory effect by 3-14 fold (Buc Calderone, et al., Curr. Med. Chem. 2002).
Vitamin C: Cancer’s “silver bullet”
1. Vitamin C alone has been found to have cytotoxic effects against most cancer cell lines in vitro. These in vitro concentrations are easily achievable in vivo with IV C. The mechanism appears to be intracellular accumulation of H2O2 with low catalase enzyme activity native to cancer cells. (Dr. Mark Levine, NIH division of Diabetes and Kidney diseases).
2. Vit C has also been found to potentiate the effects of chemotherapy drugs (Zaizen, et al., J cancer Res Lin Oncol, 1986; Prasad, et al, Pol J Pharmacol and Pharm, 1992; Koch and Biaglow, J Cell Physiol, 1978) and radiation therapy (Hanck, Prog Clin Biol Res, 1988).
OXYGEN
Oxygen breathing may be a cheaper and safer alternative to exogenous erythropoietin (EPO)
Recently discovered “normobaric oxygen paradox” demonstrates that renal tissue can be stimulated to increase EPO production via a simple pattern of oxygen breathing at normal atmospheric pressures. This leads directly to the hypothesis that oxygen breathing may provide chemotherapy patients with a convenient and inexpensive alternative to ESAs. Stimulating endogenous EPO production eliminates the small risk of immune system reaction associated with ESAs. Further, the endogenous physiological EPO doses provided by this method may be safer, in terms of cancer mortality, than the exogenous pharmacological doses inherent in ESA administration.
R. Burk Medical Hypothesis published on line 5/ 11/ 07
Rapidly growing tumors are more sensitive to chemotherapy than slow-growing tumors.
Studies at George Washington University, National Cancer Institute and M.D. Anderson Hospital & Tumor Institute tested and proved that insulin does potentiate the effects of chemotherapy.
“…Hence, the results of our experiments indicate that tumor-specific growth stimulatory hormones can be utilized to overcome the cyto-kinetic drug resistance. …thereby render subpopulations of tumor cells vulnerable to the lethal effects of cell cycle-active drugs that otherwise would have remained inert to their effects and might have constituted a potential source of late treatment failure.”
DIPYRIDAMOLE
An inhibitor of nucleoside transport
ӻDipyridamole for Pancreatic Cancer
weeksmd.com/2012/01/dipyridamole-for-pancreatic-cancer/
ӻDipyridamole and colon cancer РWeeksMD | WeeksMD
weeksmd.com/2012/04/dipyridamole-and-colon-cancer/
”ªDipyridamole as a chemotherapy potentiating agent – WeeksMD …
weeksmd.com/…/dipyridamole-as-a-chemotherapy-potentiating-agent/
”ªTargeting cancer cells with chemo-potentiating drug Dipyridamole …
weeksmd.com/…/targeting-cancer-cells-with-chemo-potentiating-drug- dipyradamole/