The outcomes of chemotherapy have been unsatisfactory with the palpable side effects. We hypothesized that natural products might help improve chemotherapy with few side effects. Recently, we came across the bioactive...The outcomes of chemotherapy have been unsatisfactory with the palpable side effects. We hypothesized that natural products might help improve chemotherapy with few side effects. Recently, we came across the bioactive extracts of monk fruit (Siraitia grosvenori) with anticancer activity. We then investigated if these extracts might have chemosensitizing effect to improve the efficacy of drugs clinically used today. Four different drugs, cisplatin (CPL), carboplatin (CBL), mitomycin C (MMC), and gemcitabine (GEM), were used in this study. Human bladder cancer T24 cells were treated with each drug itself or drug combined with either LLE or MOG (two types of monk fruit extracts). Cell viability was determined to assess anticancer effect and also explored the anticancer mechanism of such combinations, focusing on the status of glycolysis, cell cycle, and chromatin structure. Cell viability test showed that all drugs had anticancer activity, reducing cell viability, but only CPL showed the enhanced anticancer effect when combined with LLE (not with MOG). The rest of three drugs had no such effects with LLE or MOG. The CPL/LLE combination was found to disrupt glycolysis, by inhibiting hexokinase activity, resulted in the decreased ATP synthesis. This combination also blocked the cell cycle progression, due to a G1 cell cycle arrest. Moreover, the two epigenetic regulators, DNA methyltransferase and histone deacetylase, were inactivated with the combination, indicating chromatin modifications. Ultimately, these treated cells were found to undergo apoptosis. In conclusion, anticancer activity of CPL can be significantly enhanced with LLE. This chemosensitizing effect is attributed to the glycolysis inhibition, a G1 cell cycle arrest, and chromatin modifications, ultimately leading to apoptosis. Thus, certain natural products such as LLE could be used as an adjuvant agent in current chemotherapy, improving the drug efficacy but minimizing side effects.展开更多
Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we inv...Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we investigated if the bioactive extracts of monk fruit, mogrosides, with potential anticancer activity might have anticancer effect against prostate and bladder cancer cells. Four of commercial products made of mogrosides known as Lakanto<sup>ò</sup> (LKT) products, LK1, LK2, LLE, and MOG, were then tested. A dose-dependent study at given concentrations of four products showed that LK1 and LK2 had little effects, while LLE and MOG showed a significant cell viability reduction in both PC-3 and T24 cells. To explore the anticancer mechanism of such products, cell cycle analysis was first performed. Such analysis revealed that LLE and MOG, not LK1 and LK2, led to a G<sub>1</sub> cell cycle arrest. Potential induction of endoplasmic reticulum (ER) stress was next examined because it is known to be linked to a cell cycle arrest. The three key regulators involved in ER stress were all up-regulated with LLE or MOG, indicating induction of ER stress. As ER stress is also known to induce apoptosis, this possibility was tested. The two apoptotic regulators were modulated in a specific manner with LLE or MOG, indicating induction of apoptosis. Lastly, to validate anticancer effect of LLE or MOG, anticancer effect of four chemotherapeutic drugs was also assessed in comparison with that of LLE/MOG. None of drugs had any effects but two products showed significant anticancer effect. In conclusion, two monk fruit products, LLE and MOG, demonstrated anticancer activity against PC-3 and T24 cells, significantly reducing cell viability and ultimately inducing apoptosis. Therefore, these two LKT products with few side effects may have clinical implications in the treatment of urological cancers.展开更多
Buddhist monk Lin Daoren(790-850,from Xi'an,Shaanxi Province)was a specialist of traumatology and orthopedics of the Tang Dynasty.Secrets of Treating Wounds and Rejoining Fractures(Li Shang Xu Duan Fang)written by...Buddhist monk Lin Daoren(790-850,from Xi'an,Shaanxi Province)was a specialist of traumatology and orthopedics of the Tang Dynasty.Secrets of Treating Wounds and Rejoining Fractures(Li Shang Xu Duan Fang)written by him is the first extant monography on traumatology and orthopedics in China.According to the preface of the book,he had profound medical knowledge especially about the theory,diagnosis and treatment for wounds and fractures.展开更多
文摘The outcomes of chemotherapy have been unsatisfactory with the palpable side effects. We hypothesized that natural products might help improve chemotherapy with few side effects. Recently, we came across the bioactive extracts of monk fruit (Siraitia grosvenori) with anticancer activity. We then investigated if these extracts might have chemosensitizing effect to improve the efficacy of drugs clinically used today. Four different drugs, cisplatin (CPL), carboplatin (CBL), mitomycin C (MMC), and gemcitabine (GEM), were used in this study. Human bladder cancer T24 cells were treated with each drug itself or drug combined with either LLE or MOG (two types of monk fruit extracts). Cell viability was determined to assess anticancer effect and also explored the anticancer mechanism of such combinations, focusing on the status of glycolysis, cell cycle, and chromatin structure. Cell viability test showed that all drugs had anticancer activity, reducing cell viability, but only CPL showed the enhanced anticancer effect when combined with LLE (not with MOG). The rest of three drugs had no such effects with LLE or MOG. The CPL/LLE combination was found to disrupt glycolysis, by inhibiting hexokinase activity, resulted in the decreased ATP synthesis. This combination also blocked the cell cycle progression, due to a G1 cell cycle arrest. Moreover, the two epigenetic regulators, DNA methyltransferase and histone deacetylase, were inactivated with the combination, indicating chromatin modifications. Ultimately, these treated cells were found to undergo apoptosis. In conclusion, anticancer activity of CPL can be significantly enhanced with LLE. This chemosensitizing effect is attributed to the glycolysis inhibition, a G1 cell cycle arrest, and chromatin modifications, ultimately leading to apoptosis. Thus, certain natural products such as LLE could be used as an adjuvant agent in current chemotherapy, improving the drug efficacy but minimizing side effects.
文摘Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we investigated if the bioactive extracts of monk fruit, mogrosides, with potential anticancer activity might have anticancer effect against prostate and bladder cancer cells. Four of commercial products made of mogrosides known as Lakanto<sup>ò</sup> (LKT) products, LK1, LK2, LLE, and MOG, were then tested. A dose-dependent study at given concentrations of four products showed that LK1 and LK2 had little effects, while LLE and MOG showed a significant cell viability reduction in both PC-3 and T24 cells. To explore the anticancer mechanism of such products, cell cycle analysis was first performed. Such analysis revealed that LLE and MOG, not LK1 and LK2, led to a G<sub>1</sub> cell cycle arrest. Potential induction of endoplasmic reticulum (ER) stress was next examined because it is known to be linked to a cell cycle arrest. The three key regulators involved in ER stress were all up-regulated with LLE or MOG, indicating induction of ER stress. As ER stress is also known to induce apoptosis, this possibility was tested. The two apoptotic regulators were modulated in a specific manner with LLE or MOG, indicating induction of apoptosis. Lastly, to validate anticancer effect of LLE or MOG, anticancer effect of four chemotherapeutic drugs was also assessed in comparison with that of LLE/MOG. None of drugs had any effects but two products showed significant anticancer effect. In conclusion, two monk fruit products, LLE and MOG, demonstrated anticancer activity against PC-3 and T24 cells, significantly reducing cell viability and ultimately inducing apoptosis. Therefore, these two LKT products with few side effects may have clinical implications in the treatment of urological cancers.
文摘Buddhist monk Lin Daoren(790-850,from Xi'an,Shaanxi Province)was a specialist of traumatology and orthopedics of the Tang Dynasty.Secrets of Treating Wounds and Rejoining Fractures(Li Shang Xu Duan Fang)written by him is the first extant monography on traumatology and orthopedics in China.According to the preface of the book,he had profound medical knowledge especially about the theory,diagnosis and treatment for wounds and fractures.
