Anti-Tumor Effects of Natural Products Maharishi Amrit Kalash-4 (MAK-4) and Maharishi Amrit Kalash-5 (MAK-5) on Cell Transformation In Vitro and in Liver Carcinogenesis in Mice.
Nineteenth Annual Convention of Indian Association for Cancer Research and Symposium on Cancer Biology, Amala Cancer Hospital and Research Center, Thrissur, India, January 21-23, 2000.
F. Ferrari,* W.L. Hsiao,** G. Gerardi,* M. Statuto,Ú G. Mazzoleni,‡ M. Marra,§ H. Sharma, and D. Di Lorenzo.*
**Laboratory of Biotechnology, Civic Hospital of Brescia, 25123 Brescia, Italy
**Department of Biology, The Hong Kong University of Science and Technology, Hong Kong, China
Ú Institute of General Pathology, School of Medicine, University of Milan, 20100 Milan, Italy
‡ Unit of General Pathology and Immunology, School of Medicine, University of Brescia, 25123 Brescia, Italy
§ Center of Cytology, Gerontological Research Department of I.N.R.C.A., 60121 Ancona, Italy
Department of Pathology, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210 USA
Background: Maharishi Amrit Kalash-4 (MAK-4) and Maharishi Amrit Kalash-5 (MAK-5) are herbal mixtures with anticancer and anticarcinogenic properties. This investigation evaluated the cancer-inhibiting effects of MAK-4 and MAK-5 in vitro and in vivo. Methods: Aqueous extracts of MAK-4 and MAK-5 were tested for effects on ras-induced cell transformation in the Rat 6 cell line assessed by focus formation assay. Urethane-treated mice were put on a standard pellet diet or a diet supplemented with MAK-4 and MAK-5. At 36 weeks, livers were examined for tumors, sera for oxygen radical absorbance capacity (ORAC), and liver homogenates for enzyme activities of glutathione peroxidase (GPX), glutathione-S-transferase (GST), and NAD(P)H: quinone reductase (QR). Liver fragments of MAK-fed mice were analyzed for connexin (cx) protein expression. Results: MAK-5 and a combination of MAK-5 plus MAK-4, inhibited ras-induced cell transformation. There was a 46% reduction in the number of mice that developed liver nodules when fed with MAK. MAK-treated mice had a significantly higher ORAC (two-sided p<0.05) compared to controls (200.2 + 33.7 vs. 152.2 + 15.7 ORAC units, respectively). MAK-treated mice had significantly higher activities of GPX, GST, and QR compared to controls (two-sided P<0.05, p<0.01, and p<0.01, respectively). Livers of MAK-treated mice showed a time-dependent increased expression of cx32. Conclusions: A MAK-supplemented diet inhibits liver carcinogenesis in urethane-treated mice. Possible mechanisms involving inhibition of oxidative damage and up-regulation of connexin expression are discussed.
MAK-4 is now called Amrit Kalash Nectar.
MAK-5 is now called Amrit Kalash Ambrosia.
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