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
The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycop...The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycoprotein(P-gp) in tumor cells. Here, we report a novel chemosensitizing agent, XMD8-92,which can down-regulate P-gp. To enhance the specificity of MDR chemotherapy, a promising nanotheranostic micelle system based on poly(ethylene glycol)-blocked-poly(L-leucine)(PEG-b-Leu) was developed to simultaneously carry the anticancer drug doxorubicin, chemosensitizing agent XMD8-92, and superparamagnetic iron oxide nanoparticles(SPIOs). Featured with MDR environmentally responsive dual-targeting capability, controllable drug delivery, and efficient magnetic resonance(MR) imaging characteristics, the prepared nanotheranostics(DXS@NPs) showed outstanding in vitro cytotoxicity on MDR cells(SCG 7901/VCR) with only 53% of cells surviving compared to 90% of DOX-treated cells.Furthermore, efficient tumor inhibition and highly reduced systemic toxicity were exhibited by MDR tumor-bearing mice treated with DXS@NPs. Overall, the environmentally responsive dual-targeting nanotheranostics represent a promising approach for overcoming cancer MDR.展开更多
The endocrine changes of cancer patients on initial confirmed diagnosis and during chemotherapy havebeen gradually realized and clarified, as well as the dependences of different tumors on corresponding hormones. The ...The endocrine changes of cancer patients on initial confirmed diagnosis and during chemotherapy havebeen gradually realized and clarified, as well as the dependences of different tumors on corresponding hormones. The prevalent endocrinotherapy suppresses tumor progression through downregulating dependent hormone level or completely inhibitting its combination with receptors. Because of the different and even antagonistic mechanisms, endocrinotherapy should not be used with chemotherapy at the same time, or it will reduce the chemotherapeutic efficacy, which is a widely accepted principle in clinic.展开更多
Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as ce...Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably throm-bosis.Furthermore,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting mechanism.Hence,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive chemosensitization.On one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP chemotherapy.Simultaneously,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting DNA repair.In essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.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.
基金supported by the National Basic Research Development Program of China(2017YFA0205201 and 2018YFA0107301)the National Natural Science Foundation of China(81422023,81871404,81603015,U1705281,and U1505221)+1 种基金the Fundamental Research Funds for the Central Universities(20720160065,and 20720150141)the Program for New Century Excellent Talents in University,China(NCET-13-0502)
文摘The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycoprotein(P-gp) in tumor cells. Here, we report a novel chemosensitizing agent, XMD8-92,which can down-regulate P-gp. To enhance the specificity of MDR chemotherapy, a promising nanotheranostic micelle system based on poly(ethylene glycol)-blocked-poly(L-leucine)(PEG-b-Leu) was developed to simultaneously carry the anticancer drug doxorubicin, chemosensitizing agent XMD8-92, and superparamagnetic iron oxide nanoparticles(SPIOs). Featured with MDR environmentally responsive dual-targeting capability, controllable drug delivery, and efficient magnetic resonance(MR) imaging characteristics, the prepared nanotheranostics(DXS@NPs) showed outstanding in vitro cytotoxicity on MDR cells(SCG 7901/VCR) with only 53% of cells surviving compared to 90% of DOX-treated cells.Furthermore, efficient tumor inhibition and highly reduced systemic toxicity were exhibited by MDR tumor-bearing mice treated with DXS@NPs. Overall, the environmentally responsive dual-targeting nanotheranostics represent a promising approach for overcoming cancer MDR.
文摘The endocrine changes of cancer patients on initial confirmed diagnosis and during chemotherapy havebeen gradually realized and clarified, as well as the dependences of different tumors on corresponding hormones. The prevalent endocrinotherapy suppresses tumor progression through downregulating dependent hormone level or completely inhibitting its combination with receptors. Because of the different and even antagonistic mechanisms, endocrinotherapy should not be used with chemotherapy at the same time, or it will reduce the chemotherapeutic efficacy, which is a widely accepted principle in clinic.
基金supported by the Guangdong Basic and Applied Basic Research Foundation of China(No.2021A1515011050)President Foundation of the Third Affiliated Hospital of Southern Medical University(No.YM202202)+1 种基金the Health Economics Association Research Program of Guangdong Province(No.2022-WJZD-20)the Higher Education Teaching Management Association Curriculum Thinking and Administration Program of Guangdong Province(No.X-KCSZ2021082).
文摘Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably throm-bosis.Furthermore,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting mechanism.Hence,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive chemosensitization.On one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP chemotherapy.Simultaneously,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting DNA repair.In essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.
