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Phytonutrients
Published in Parimelazhagan Thangaraj, Medicinal Plants, 2018
Ranganathan Kumar, Sulaxana Kumari Chauhan, Subramanian Vijayalakshmi, Shanmugam Nadanasabapathi
The monoterpene D-limonene, the main component of the oil from citrus peel, was also found to protect against cancer; it produces glutathione transferases, a family of phase II detoxification enzymes (Crowell 1997; Gould 1997). D-limonene was given a GRAS (generally regarded as safe) status for its use as a flavouring agent. D-limonene was proved to be a good candidate for human clinical chemoprevention trial evaluation possessing no toxicity in humans. Perillyl alcohol, a metabolite of limonene, has passed through phase I clinical trials in patients with advanced malignancies (Ripple et al. 1998).
RAS Signaling in Melanoma Development and Prevention
Published in Sanjiv S. Agarwala, Vernon K. Sondak, Melanoma, 2008
Apomine, a novel biphosphonate ester with nonmyelosuppressive properties, has been noted to activate the farnesoid X receptor, increase the rate of degradation of HMG-CoA reductase, inhibit cell proliferation, and induce tumor-cell apoptosis (51). It also appears to have a membrane-mediated cytolytic mechanism, independent of NRAS farnesylation and caspase-3 activation (52). This agent was evaluated in a murine chemoprevention model. Powell et al. used a transgenic mouse model, the TPRAS model, that expressed a human-activated Ha-RAS gene driven by a mouse tyrosinase promoter, in which cutaneous melanomas could be induced with topical application of 7,12-dimethylbenz[a] anthracene (DMBA) (53). In this model, topical application of apomine to TPRAS mice resulted in a 55% reduction in melanoma incidence (54). The TPRAS model was used to screen another agent targeting RAS signaling, perillyl alcohol, a monoterpene isolated from essential oils (54,55). In vitro data had suggested that perillyl alcohol inhibited detectable RAS protein expression and the activation of downstream targets, including mitogen-activated protein kinases and Akt (55). Topical application of perillyl alcohol to TPRAS mice resulted in delay of melanoma and a 25% to 35% reduction in melanoma incidence (55). Early phase studies with topical perillyl alcohol have been initiated at the University of Arizona.
Effectiveness of Ketogenic Diets on the Survival of Adult Oncological Patients
Published in Nutrition and Cancer, 2021
A study published by Santos et al evaluated 32 patients with recurrent GM. Seventeen patients were randomized to receive a treatment with perillyl alcohol (POH) (55 mg, 0.3% intranasal) associated with KD during 3 months and 15 patients to a control group with a standard diet. Only 17 patients completed the study (9 patients in the intervention group). The caloric composition of the KD was 50% lipids, 25% carbohydrates and 1.5 g/kg/day of proteins. After 3 months of follow-up, 77.8% of patients in the interventional group showed partial response to treatment, observing a reduction in tumor size and peritumoral edema on the MRI, neurological stability, decreased corticosteroid requirement and improvement in general conditions. An 11.1% of patients in the interventional group presented disease progression (vs. 50% in the control group), either due to increased tumor size or the appearance of new lesions. At day 90 , the tumor area observed in the MRI was smaller in the interventional group compared to initial images (p = 0.035), but not in the control group (p = 0.687) (41). A previous study of the same group using POH alone in GM patients did not observe the same regression magnitude of peritumoral edema in lesions (42). The authors conclude that this study suggests that KD associated with intranasal POH may be a viable option as adjuvant treatment in patients with recurrent GM (41). However, more studies with a larger number of patients will be required to assess its efficacy.
Therapeutic Perspective of Temozolomide Resistance in Glioblastoma Treatment
Published in Cancer Investigation, 2021
Qin Xia, Liqun Liu, Yang Li, Pei Zhang, Da Han, Lei Dong
Some agents inhibit GSCs and synergize with TMZ to improve efficacy (Table 1). For example, the combination of LCC-09 with TMZ or LCC-09 alone inhibits the stemness and tumorigenicity of TMZ-resistant cells (86). Kitabayashi et al. reported that kenpaullone targeted GSCs and acted as a TMZ enhancer; the combination of kenpaullone with TMZ inhibited the viability of GSCs and glioma cell lines and suppressed the stemness phenotype. Compared with TMZ alone, the combined therapy significantly promoted survival time in mouse models (87). Marin-Ramos et al. used a conjugate of TMZ and perillyl alcohol, namely NEO212, which is effective against TMZ-resistant cancer cells and has a cytotoxicity 10-fold higher than that of TMZ against GSCs (88). They found that NEO212 inhibited GSC invasion and migration, demonstrating its clinical value. Doan et al. found that 3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol (THTMP) regulated the EGFR and CSC pathways to induce apoptosis and cell cycle arrest, thereby suppressing proliferation and migration of GB cells and reversing TMZ resistance (89). These studies suggest that the combination of TMZ and drugs that inhibit GSCs are feasible for the treatment of GB.
Biological activity of terpene compounds produced by biotechnological methods
Published in Pharmaceutical Biology, 2016
Roman Paduch, Mariusz Trytek, Sylwia K. Król, Joanna Kud, Maciej Frant, Martyna Kandefer-Szerszeń, Jan Fiedurek
In the present study, the terpenes tested showed no free radical scavenging activity. This may have been an effect of the application of relatively low concentrations of these compounds, because when higher concentrations were used, antioxidant activity was detected. Similar to our results, Yang et al. (2010) have found that α-pinene had an only slight DPPH-radical scavenging activity compared with limonene. The mechanism of the action of perillyl alcohol, which is a limonene derivative, is based not only on its antioxidant properties but also on its tumour-modifying effects and its general effects on cell biology (Wargovich 2001). It is also worth mentioning that in this present study, the (S)-(+)-stereoisomer of carvone had a 5.5-fold higher antioxidative activity than the (R)-(−)-stereoisomer. This finding indicates that steric limitations may also influence the ROS scavenging potential of compounds.