acid is not a "vitamin". Lipoic acid is not a "vitamin".
I find it highly unusual that these favorable scientific research results came from Japan, Norway and Germany. Funny that.
A combination of indol-3-carbinol and genistein synergistically induces apoptosis in human colon cancer HT-29 cells by inhibiting Akt phosphorylation and progression of autophagy.
Nakamura Y, Yogosawa S, Izutani Y, Watanabe H, Otsuji E, Sakai T.
Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan. nakamura@koto.kpu-m.ac.jp
Abstract
BACKGROUND: The chemopreventive effects of dietary phytochemicals on malignant tumors have been studied extensively because of a relative lack of toxicity. To achieve desirable effects, however, treatment with a single agent mostly requires high doses. Therefore, studies on effective combinations of phytochemicals at relatively low concentrations might contribute to chemopreventive strategies.
RESULTS: Here we found for the first time that co-treatment with I3C and genistein, derived from cruciferous vegetables and soy, respectively, synergistically suppressed the viability of human colon cancer HT-29 cells at concentrations at which each agent alone was ineffective. The suppression of cell viability was due to the induction of a caspase-dependent apoptosis. Moreover, the combination effectively inhibited phosphorylation of Akt followed by dephosphorylation of caspase-9 or down-regulation of XIAP and survivin, which contribute to the induction of apoptosis. In addition, the co-treatment also enhanced the induction of autophagy mediated by the dephosphorylation of mTOR, one of the downstream targets of Akt, whereas the maturation of autophagosomes was inhibited. These results give rise to the possibility that co-treatment with I3C and genistein induces apoptosis through the simultaneous inhibition of Akt activity and progression of the autophagic process. This possibility was examined using inhibitors of Akt combined with inhibitors of autophagy. The combination effectively induced apoptosis, whereas the Akt inhibitor alone did not.
CONCLUSION: Although in vivo study is further required to evaluate physiological efficacies and toxicity of the combination treatment, our findings might provide a new insight into the development of novel combination therapies/chemoprevention against malignant tumors using dietary phytochemicals.
DHA alters expression of target proteins of cancer therapy in chemotherapy resistant SW620 colon cancer cells.
Slagsvold JE, Pettersen CH, Størvold GL, Follestad T, Krokan HE, Schønberg SA.
Norwegian University of Science and Technology, Trondheim, Norway.
Abstract
Diets rich in n-3 polyunsaturated fatty acids (PUFAs) have been associated with a reduced risk of several types of cancer. Recent reports have suggested that these PUFAs enhance the cytotoxic effect of cancer chemoradiotherapy. The effect of docosahexaenoic acid (DHA) on key cell cycle regulators and target proteins of cancer therapy was investigated in the human malign colon cancer cell line SW620. Cell cycle check point proteins such as p21 and stratifin (14-3-3 sigma) increased at mRNA and protein level, whereas cell cycle progression proteins such as cell division cycle 25 homolog and cyclin-dependent kinase 1 decreased after DHA treatment. Protein levels of inhibitors of apoptosis family members associated with chemotherapy resistance and cancer malignancy, survivin and livin, decreased after the same treatment: likewise the expression of NF-kappaB. Levels of the proapoptotic proteins phosphorylated p38 MAPK and growth arrest-inducible and DNA damage-inducible gene 153/C/EBP-homologous protein (CHOP) increased. The results indicate that DHA treatment causes simultaneous cell cycle arrest in both the G1 and G2 phase. In conclusion, DHA affects several target proteins of chemotherapy in a favorable way. This may explain the observed enhanced chemosensitivity in cancer cells supplemented with n-3 PUFAs and encourage further studies investigating the role of n-3 PUFAs as adjuvant to chemotherapy and radiotherapy in vivo.
PMID: 20574922
Apoptosis. 2005 Mar;10(2):359-68.
alpha-Lipoic acid induces apoptosis in human colon cancer cells by increasing mitochondrial respiration with a concomitant O2-*-generation.
Wenzel U, Nickel A, Daniel H.
Molecular Nutrition Unit, Department of Food and Nutrition, Technical University of Munich, Hochfeldweg 2, D-85350, Freising, FRG. uwenzel@wzw.tum.de
Abstract
The antioxidant alpha-lipoic acid (ALA) has been shown to affect a variety of biological processes associated with oxidative stress including cancer. We determined in HT-29 human colon cancer cells whether ALA is able to affect apoptosis, as an important parameter disregulated in tumour development. Exposure of cells to ALA or its reduced form dihydrolipoic acid (DHLA) for 24 h dose dependently increased caspase-3-like activity and was associated with DNA-fragmentation. DHLA but not ALA was able to scavenge cytosolic O2-* in HT-29 cells whereas both compounds increased O2-*-generation inside mitochondria.
Increased mitochondrial O2-*-production was preceded by an increased influx of lactate or pyruvate into mitochondria and resulted in the down-regulation of the anti-apoptotic protein bcl-X(L). Mitochondrial O2-*-generation and apoptosis induced by ALA and DHLA could be prevented by the O2-*-scavenger benzoquinone. Moreover, when the lactate/pyruvate transporter was inhibited by 5-nitro-2-(3-phenylpropylamino) benzoate, ALA- and DHLA-induced mitochondrial ROS-production and apoptosis were blocked. In contrast to HT-29 cells, no apoptosis was observed in non-transformed human colonocytes in response to ALA or DHLA addition.
In conclusion, our study provides evidence that ALA and DHLA can effectively induce apoptosis in human colon cancer cells by a prooxidant mechanism that is initiated by an increased uptake of oxidizable substrates into mitochondria.
PMID: 15843897