Asiatic acid(AA), a pentacyclic triterpene found in Centella asiatica, displays significant antiproliferative effects on cancer cells in vitro although the underlying mechanism of this effect remains unknown. This stu...Asiatic acid(AA), a pentacyclic triterpene found in Centella asiatica, displays significant antiproliferative effects on cancer cells in vitro although the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer both in vivo and in vitro. Using the MTT assay, AA was found to induce apoptosis in a dose- and timedependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3(LC3) and decreased the expression of p62.Furthermore, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species(ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen(PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth both in vitro and in vivo and that the associated apoptosis is mediated through mitochondrial damage.展开更多
The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signa...The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of cancer.BRAF mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among others.BRAF is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors.展开更多
文摘Asiatic acid(AA), a pentacyclic triterpene found in Centella asiatica, displays significant antiproliferative effects on cancer cells in vitro although the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer both in vivo and in vitro. Using the MTT assay, AA was found to induce apoptosis in a dose- and timedependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3(LC3) and decreased the expression of p62.Furthermore, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species(ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen(PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth both in vitro and in vivo and that the associated apoptosis is mediated through mitochondrial damage.
基金supported by the Natural Science Foundation of China(grant number 82002456)China Postdoctoral Science Foundation(grant number 2022M723207)+10 种基金the Medical Scientific Research Foundation of Zhejiang Province,China(grant number 2023KY666)Zhejiang Traditional Chinese Medicine Science Fund Project(grant number 2024ZL372)Qiantang Cross Fund Project(grant number 2023-16)National Natural Science Foundation of China of Zhejiang Cancer Hospital Cultivation Project(grant number PY2023006)the Medical Scientific Research Foundation of Zhejiang Province,China(grant number 2024KY812)the Natural Science Foundation of Zhejiang Province(grant number LQ24H160036)Beijing Health Technologies Promotion Program[grant number BHTPP2022041]Peking University Clinical Scientist Training Program and the Fundamental Research Funds for the Central Universities[grant number BMU2024PYJH010]Science Foundation of Peking University Cancer Hospital[grant number PY202333]the Beijing Natural Science Foundation[grant number 7232248]Beijing Hospitals Authority Youth Programme[grant number QML20231902].
文摘The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of cancer.BRAF mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among others.BRAF is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors.