Natural Approaches to Enhancing Chemotherapy Efficacy
Fish Oil and Chemotherapy
Fish oil may enhance the effectiveness of cancer chemotherapy drugs. A study compared different fatty acids on colon cancer cells to see if they could enhance Mitomycin C, a chemotherapy drug efficacy. Eicosapentaenoic acid (EPA) concentrated from fish oil was shown to sensitize colon cancer cells to Mitomycin C (Tsai et al. 1997). It should be noted that fish oil also suppresses the formation of prostaglandin E2, an inflammatory hormone-like substance involved in cancer cell propagation.
In another study, a group of dogs with lymphoma were randomized to receive either a diet supplemented with arginine and fish oil or just soybean oil. Dogs on the fish oil and arginine diet had a significantly longer disease-free survival time than dogs on the soybean oil (Ogilvie et al. 2000).
Caffeine and Chemotherapy
The use of caffeine in combination with chemotherapy has been shown to enhance the cytotoxicity of chemotherapy drugs. Caffeine occurs naturally in green tea and has been shown to potentiate the anticancer effects of tea polyphenols. In SKH-1 mice at high risk of developing malignant and nonmalignant tumors, oral administration of caffeine (as sole source of drinking fluid for 18-23 weeks) inhibited the formation and decreased the size of both nonmalignant tumors and malignant tumors (Lou et al. 1999).
In cancer, p53 gene mutations are the most common genetic alterations observed, occurring in 50-60% of patients, including those with carcinomas and sarcomas. Caffeine has been shown to potentiate the destruction of p53 defective cells by inhibiting growth in the G2 phase. This ability of caffeine is important because the basis of many anticancer therapies is to damage tumor DNA and destroy the replicating cancer cells. Caffeine uncouples tumor cell-cycle progression by interfering with the replication and repair of DNA (Blasina et al. 1999; Ribeiro et al. 1999; Jiang et al. 2000; Valenzuela et al. 2000).
Panax Ginseng and Chemotherapy
Panax ginseng, also known as Korean ginseng, has been used in China for thousands of years as a popular remedy for varous diseases including cancer (Kang 2011). Cancers can develop resistance to chemotherapy drugs. Multidrug resistance, the principal mechanism by which many cancers develop resistance to chemotherapy drugs, is a major factor in the failure of many forms of chemotherapy (Pérez-Tomás 2006). P-glycoprotein—expressed within cancer cells—confers multidrug resistance by transporting chemotherapy drugs out of cancer cells. Researchers observed that panax ginseng extract reversed P-glycoprotein-induced multidrug resistance, which resulted in increased accumulation of chemotherapy drugs within cancer cells (Choi 2003). Also, panax ginseng extract enhanced the anti-cancer effects of the chemotherapy drug mitomycin C in stomach cancer cells (Matsunaga 1994) and potentiated the anti-tumor effects of the chemotherapy drug cisplatin in mice with ovarian cancer (Kikuchi 1991).
Quercetin and Chemotherapy
Quercetin is a flavonoid found in a broad range of foods, from grape skins and red onions to green tea and tomatoes. Quercetin’s antioxidant and anti-inflammatory properties protect cellular DNA from cancer-inducing mutations (Aherne 1999). Quercetin traps developing cancer cells in the early phases of their replicative cycle, effectively preventing further malignant development and promoting cancer cell death (Yang 2006). Furthermore, quercetin favorably modulates chemical signaling pathways that are abnormal in cancer cells (Morrow 2001; Bach 2010).
Quercetin potentiates the anti-cancer activity of the chemotherapy drug adriamycin against breast cancer cells (Scambia 1994; Staedler 2011; Du 2010a) by increasing concentrations of adriamycin within cancer cells (Li 2012). In mice with breast cancer, combining quercetin with adriamycin led to long-term, tumor-free survival, whereas mice were failed to be cured when treated with adriamycin alone (Du 2010b). Interestingly—when given together with quercetin—adriamycin inflicted substantial DNA damage to cancer cells. However, normal cells were protected against the DNA damaging effects of adriamcyin (Staedler 2011). This effect cannot be understated, as the main problem associated with the use of chemotherapy is that it inflicts damage to normal cells as well as cancer cells.
Quercetin enhances the anti-cancer activity of the chemotherapy drug cisplatin (Hofmann 1988). The concomitant administration of quercetin and cisplatin reduced tumor growth to a significantly greater degree than cisplatin alone in mice with lung cancer (Hofmann 1990).
Sulforaphane and Chemotherapy
Sulforaphane, which is an isothiocyanate, is most highly concentrated in broccoli as well as in other cruciferous vegetables (eg, brussels sprouts, cabbage and cauliflower). Sulforaphane shows promise as an adjuvant to chemotherapy. When added to the chemotherapy drug oxaliplatin, sulforaphane improved the ability of the drug to kill colon cancer cells (Kaminski 2011).
Theanine and Chemotherapy
L-theanine is a unique amino acid, naturally occurring in green tea, shown in one study to enhance Adriamycin concentration in tumors 2.7-fold and reduce tumor weight 62% over controls, whereas Adriamycin by itself did not reduce tumor weight (Sugiyama et al. 1998). Adriamycin is an anthracycline antibiotic having a wide spectrum of antitumor activity. Additionally, L-theanine was shown to reverse tumor resistance to certain chemotherapeutic drugs by forcing more of the drug to stay inside the tumor. It does not, however, increase the amount of drug in normal tissue, which sets it apart from other drugs designed to overcome multidrug resistance (Sadzuka et al. 2000a).
Theanine Makes Chemotherapy Work
In 1999 researchers performed a study testing the use of theanine in conjunction with a drug similar to doxorubicin known as idarubicin. The use of idarubicin has been tried in drug-resistant leukemia cells, but it caused toxic bone marrow suppression.
Researchers wanted to see if theanine would cause the drug idarubicin to work. In the first experiment, about one-fourth of the standard dose of idarubicin was used. At this dose, the drug usually does not work, and it also does not cause toxicity. When combined with theanine, however, idarubicin worked but still without toxicity. Tumor weight was reduced 49%, and the amount of drug in the tumors doubled. In the next experiment, theanine was added to the usual therapeutic dose of idarubicin. Theanine increased the effectiveness of idarubicin and significantly lessened usual bone marrow suppression. Leukocyte loss was reduced from 57% to 37% (Sadzuka et al. 2000c).
Part of theanine's activity can be attributed to its mimicking of glutamate, an amino acid that potentiates glutathione. Theanine crowds out glutamate transport into tumor cells. Cancer cells (in confusion) erringly take in theanine, and theanine-created glutathione results. Glutathione (created by theanine) does not detoxify like natural glutathione, and instead blocks the ability of cancer cells to neutralize cancer-killing agents. Deprived of glutathione, cancer cells cannot remove chemotherapeutic agents, and the cell dies as a result of chemical poisoning (Sadzuka et al. 2001b).