Cancer presents a significant global challenge,impacting individuals,communities,and healthcare systems worldwide[1,2].Fundamentally,cancer involves the uncontrolled growth and proliferation of cells,driven by genetic...Cancer presents a significant global challenge,impacting individuals,communities,and healthcare systems worldwide[1,2].Fundamentally,cancer involves the uncontrolled growth and proliferation of cells,driven by genetic and epigenetic alterations orchestrated by a complex array of molecular entities,including oncogenes,tumor suppressor genes,and various regulatory factors[3-5].This intricate interplay complicates early detection,often resulting in a significant mortality burden.Accounting for nearly 30%of premature deaths globally,cancer is a major barrier to increasing human life expectancy[6,7].The urgent need for continued research,innovation,and collaborative efforts highlights the importance of combating this relentless disease.展开更多
Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer...Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 μmol·L^(−1), respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD’s role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.展开更多
基金supported by the Science and Technology Development Fund,Macao SAR (Nos.0015-2022-A1 and 005/2023/SKL)University of Macao (No.MYRG-GRG2023-00160-ICMS-UMDF)the Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine,University of Macao (No.SKL-QRCM-IRG2023-011).
文摘Cancer presents a significant global challenge,impacting individuals,communities,and healthcare systems worldwide[1,2].Fundamentally,cancer involves the uncontrolled growth and proliferation of cells,driven by genetic and epigenetic alterations orchestrated by a complex array of molecular entities,including oncogenes,tumor suppressor genes,and various regulatory factors[3-5].This intricate interplay complicates early detection,often resulting in a significant mortality burden.Accounting for nearly 30%of premature deaths globally,cancer is a major barrier to increasing human life expectancy[6,7].The urgent need for continued research,innovation,and collaborative efforts highlights the importance of combating this relentless disease.
基金supported by the Science and Technology Development Fund,Macao SAR(File no.0053-2021-AGJ)the Joint Foundation of Guangdong and Macao for Science and Technology Innovation(2022A0505020024)+3 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,File No.:2020B1212030006)the Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine,University of Macao(File No.:SKL-QRCM-IRG2023-011)the Natural Science Foundation of Fujian Province(2022J01244)the Outstanding-Young Scientific Research Talents Program of Fujian Agriculture and Forestry University(XJQ202103)。
文摘Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 μmol·L^(−1), respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD’s role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
