Verapamil and Indole-3-carbinol
cheap, potential answers to drug resistance
We are seeing cases of DCA resistance. Please note that we have no idea of the nature of the drug resistance. However, here are a couple of options to consider.
Indole-3-carbinol is found in cruciferous vegetables (and available as a supplement) shown to help reverse drug resistance.
Natural Prevention: I3C and Cancer by By Terri Mitchell. Life Extension Magazine. July 2003.
Modulation of vinca-alkaloid induced P-glycoprotein expression by indole-3-carbinol . Cancer Letters. Volume 189 , Issue 2 , Page 167 A . Arora
.... In the present study, indole-3-carbinol (I3C), a well-known chemopreventive agent present in cruciferous vegetables, has been evaluated for its potential to modulate the over-expression of P-gp induced by vinblastine or vincristine, which are known inducers of mdr-1 gene. The results revealed that I3C significantly reversed the over-expression of P-gp in vinca-alkaloid induced drug resistance as evident by Western blotting using monoclonal antibody (clone JSB1). Quantization of immunostained tissue sections using image analysis technique revealed that vinblastine/ vincristine induced overexpression of P-gp was effectively reversed by I3C. The present investigation suggests that I3C can significantly inhibit the P-gp over-expression and may have utility as a dietary adjuvant in the treatment of cancer for the reversal of multiple drug resistance.
Reversal of Multidrug Resistance in Vivo by Dietary Administration of the Phytochemical Indole-3-CarbinolJames G. Christensen and Gerald A. LeBlanc. Cancer Research 56, 574-581, February 1, 1996.
Abstract: ....Collectively, these results indicate that ingestion of the common dietary constituent I3C results in its conversion to acid-condensation derivatives that sensitized MDR tumors to chemotherapeutic drugs without eliciting direct toxicity to the host.
In Vitro Antimicrobial Activity and the Mode of Action of Indole-3-Carbinol against Human Pathogenic Microorganisms. Woo Sang Sung and Dong Gun Lee. Biological & Pharmaceutical Bulletin
Vol. 30 (2007) , No. 10 1865.
The results showed that I3C arrested the cell cycle at the G2/M phase in Candida albicans. To understand the antifungal mode of action of I3C, the change in the membrane dynamics was monitored by using fluorescence changing experiments against C. albicans. The results suggest that I3C may exert antifungal activity by disrupting the structure of the cell membrane. The present study indicates that I3C has considerable antimicrobial activity, deserving further investigation for clinical applications."
A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia.
Int J Gynecol Cancer. 2006 Mar-Apr;16(2):786-90.
This study has shown significant clinical improvement in symptomatology and vulvoscopic appearance of VIN with I3C therapy.
Placebo-controlled trial of indole-3-carbinol in the treatment of CIN Gynecol Oncol. 2000 Aug;78(2):123-9.
RESULTS: None (0 of 10) of the patients in the placebo group had complete regression of CIN. In contrast 4 of 8 patients in the 200 mg/day arm and 4 of 9 patients in the 400 mg/day arm had complete regression based on their 12-week biopsy. ...
CONCLUSIONS: There was a statistically significant regression of CIN in patients treated with I-3-C orally compared with placebo.
I want to thank Sandra of the Chat room for bringing Indole-3-carbinol to our attention!
An additional note from Sandra on I3C, from the LEF site:
I3C may interfere with oral contraceptives. If pregnant or intending to become pregnant, do not use this product. Do not use if taking antacids, H2-receptor blockers (e.g. Zantac®), or proton-pump inhibitors (e.g. Nexium®), as these drugs may impede the conversion of I3C to active metabolites.
Verapamil is an inhibitor of "drug efflux pump proteins such as P-glycoprotein. This is useful as many tumor cell lines overexpress drug efflux pumps, limiting the effectiveness of cytotoxic drugs". Verapamil therefore stops cells from rejecting chemotherapy drugs. Drug pumps are widespread beyond bacteria: Candida, fungi in general, malarial parasites, Simply put, these proteins actually pump the drugs out of the cell.
"These compounds, which include verapamil and cyclosporin, generally have little or no effect by themselves on the tumor cells, but when used in conjunction with antineoplastic agents, they decrease, and in some instances eliminate, drug resistance." from P-glycoproteins and multidrug resistance.
Links to articles on Verapamil
Certain cell proteins are involved in drug resistance in a variety of cancers including small cell lung cancer and breast cancer. "After three decades of research, can we confidently define the contribution of multidrug resistance transporters to chemoresistance " Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer.
Drug resistance in pleural mesothelioma is due to P-glycoprotein expression, Modulation of vindesine and doxorubicin resistance in multidrug-resistant pleural mesothelioma cells by tumor necrosis factor-alpha.
"P-glycoprotein appears to play an important role in such cells by acting as an energy-dependent efflux pump to remove various natural product drugs from the cell before they have a chance to exert their cytotoxic effects." P-glycoproteins and multidrug resistance.
"Combination of this calcium antagonist with antineoplastic agents results in the establishment of chemosensitivity in tumor cells resistant to accepted chemotherapeutic agents and, to a lesser degree, potentiates the efficacy of such compounds in drug-sensitive malignancies."
The calcium channel blocker verapamil and cancer chemotherapy.
Very high levels of verapamil "produced an unacceptable degree of cardiac toxicity." Verapamil and adriamycin in the treatment of drug-resistant ovarian cancer patients
In mesothelioma, "The drug dose-dependently also inhibited the in vitro growth of tumor cells; "Verapamil inhibits to different extents agonist-induced Ca2+ transients in human tumor cells and in vitro tumor cell growth.
Reversal of adriamycin resistance by verapamil
in human ovarian cancer
This is what one person is using to achieve noticeable results:in a lymphoma:
12.5 mg/kg DCA - 3 times a day
80 mg verapamil 3 times a day (total is 240 mg a day)
1500 mg B1
about 10 grams omega 3 liquid oil
40 mg Lasix (to drain the lymph fluid)
64 mg Medrol (cortisone)
and 6 cups of tea with double teabags.
Articles on the use of Verapamil
Lab Rat? from the Wall Street Journal. Excellent article on protocols, including the use of Verapamil.