Improved Anticancer Effects on Various Cancers with Combinations of Chemotherapeutic Drugs or Vitamin C and D-Fraction

Sensuke Konno, Bobby Alexander, Drew Freilich, Muhammad Choudhury

Department of Urology, New York Medical College, Valhalla, USA.

DOI: 10.4236/jct.2013.44096                

Abstract

Although chemotherapy is one of several therapeutic options for cancer patients, the outcomes have been less satisfactory with palpable side effects in many cases. To help improve the efficacy of chemotherapy, we examined whether D-fraction (DF), a bioactive mushroom extract, would potentiate anticancer effects of those drugs in vitro. Seven types of cancer cell lines, including breast, lung, stomach, colon, prostate, bladder, and kidney cancers, were tested with various chemotherapeutic drugs and their combinations with DF. Compared to individual drugs alone, combinations of those drugs and DF have indeed improved anticancer activity, resulting in the significant (p < 0.05) cell viability reduction in all cancer cells. As vitamin C (VC) has been insinuated to potentiate bioactivity of DF, combination of DF (300 μg/ml) and VC (200 μM) was also examined. Such studies showed that DF/VC combination led to the drastic (≥90%) viability reductions in 6 cancer cells and the 70% reduction in 1 cancer cell type. These results were superior to those from combinations of drugs and DF. To assess if such a profound cell viability reduction by DF/VC combination might be attributed to apoptosis, this possibility was tested by Western blots. Analyses revealed that anti-apoptotic bcl-2 was down-regulated while pro-apoptotic Bax was up-regulated with DF/VC combination, indicating induction of apoptosis. It is plausible that DF/VC combination may induce apoptosis, resulting in the severe cell viability reduction. Therefore, DF may have a great potential as an adjuvant agent that can be combined with chemotherapeutic drugs or with VC for the improved treatment of various human malignancies.

Keywords

D-Fraction; Vitamin C; Chemotherapy; Apoptosis; Human Cancers; Maitake

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	World Health Organization, “Cancer Fact Sheet,” 2011. http://www.who.int/media centre/factsheets/fs297/en/
[2]	A. K. Maiti, “Genetic Determinants of Oxidative StressMediated Sensitization of Drug-Resistant Cancer Cells,” International Journal of Cancer, Vol. 130, No. 1, 2012, pp. 1-9. doi:10.1002/ijc.26306
[3]	R. J. Motzer and P. Russo, “Systemic Therapy for Renal Cell Carcinoma,” Journal of Urology, Vol. 163, No. 2, 2000, pp. 408-417. doi:10.1016/S0022-5347(05)67889-5
[4]	M. Fung-Kee-Fung, T. Oliver, L. Elit, A. Oza, H. W. Hirte and P. Bryson, “Optimal Chemotherapy Treatment for Women with Recurrent Ovarian Cancer,” Current Oncology, Vol. 14, No. 5, 2007, pp. 195-208. doi:10.3747/co.2007.148
[5]	T. Mizuno and C. Zhuang, “Maitake, Grifola frondosa: Pharmacological Effects,” Food Reviews International, Vol. 11, No. 1, 1995, pp. 135-149. doi:10.1080/87559129509541024
[6]	K. Adachi, H. Nanba and H. Kuroda, “Potentiation of Host-Mediated Antitumor Activity in Mice by b-Glucan Obtained from Grifola frondosa (Maitake),” Chemical and Pharmaceutical Bulletin (Tokyo), Vol. 35, No. 1, 1987, pp. 262-270. doi:10.1248/cpb.35.262
[7]	I. Hishida, H. Nanba and H. Kuroda, “Antitumor Activity Exhibited by Orally Administered Extract from Fruit Body of Grifola frondosa (Maitake),” Chemical and Pharmaceutical Bulletin (Tokyo), Vol. 36, No. 5, 1988, pp. 1819-1827. doi:10.1248/cpb.36.1819
[8]	C. Q. Gu, J. W. Li and F. H. Chao, “Inhibition of Hepatitis B Virus by D-Fraction from Grifola frondosa: Synergistic Effect of Combination with Interferon-a in HepG2 2.2.15,” Antiviral Research, Vol. 72, No. 2, 2006, pp. 162-165. doi:10.1016/j.antiviral.2006.05.011
[9]	National Cancer Institute, “Developmental Therapeutics Program: In-Vitro Anti-HIV Drug Screening Results,” National Science Council F195001, Washington DC, 1992.
[10]	Maitake Products, Inc., “D-Fraction Obtained IND for Clinical Study,” Corporate Publication, Paramus, 1998.
[11]	S. Glauco, F. Jano, G. Paolo and S. Konno, “Safety of Maitake D-Fraction in Healthy Subjects: Assessment of Common Hematologic Parameters,” Alternative and Complementary Therapies, Vol. 10, No. 4, 2004, pp. 228-230. doi:10.1089/1076280041580341
[12]	F. Morishige, “The Role of Vitamin C in Tumor Therapy (Human),” In: F. I. Meyskens Jr. and K. N. Parasad, Eds., Vitamins and Cancer: Human Cancer Prevention by Vitamins and Micronutrients, Humana Press, Clifton, 1986, pp. 399-427.
[13]	J. A. Mordente, S. Konno, Y. Chen, J. M. Wu, H. Tazaki and C. Mallouh, “The Effects of Brefeldin A (BFA) on Cell Cycle Progression Involving the Modulation of the Retinoblastoma Protein (pRB) in PC-3 Prostate Cancer Cells,” Journal of Urology, Vol. 159, No. 1, 1998, pp. 275-279. doi:10.1016/S0022-5347(01)64081-3
[14]	M. F. Ullah, S. H. Bhat, E. Hussain, F. Abu-Duhier, A. Ahmad and S. M. Hadi, “Ascorbic Acid in Cancer Chemoprevention: Translational Perspectives and Efficacy,” Current Drug Targets, Vol. 13, No. 14, 2012, pp. 1757-1771. doi:10.2174/138945012804545669
[15]	Q. Chen, M. G. Espey, M. C. Krishna, J. B. Mitchell, C. P. Corpe, G. R. Buettner, E. Shacter and M. Levine, “Pharmacologic Ascorbic Acid Concentrations Selectively Kill Cancer Cells: Action as a Pro-Drug to Deliver Hydrogen Peroxide to Tissues,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 38, 2005, pp. 13604-13609. doi:10.1073/pnas.0506390102
[16]	K. W. Yip and J. C. Reed, “Bcl-2 Family Proteins and Cancer,” Oncogene, Vol. 27, No. 50, 2008, pp. 6398406. doi:10.1038/onc.2008.307