title: Identification of genes involved in the regulation of 14-deoxy-11,12-didehydroandrographolide-induced toxicity in T-47D mammary cells.
abstract: 14-Deoxy-11,12-didehydroandrographolide is one of the principle compounds of the medicinal plant, Andrographis paniculata Nees. This study explored the mechanisms of 14-deoxy-11,12-didehydroandrographolide-induced toxicity and non-apoptotic cell death in T-47D breast carcinoma cells. Gene expression analysis revealed that 14-deoxy-11,12-didehydroandrographolide exerted its cytotoxic effects by regulating genes that inhibit the cell cycle or promote cell cycle arrest. This compound regulated genes that are known to reduce/inhibit cell proliferation, induce growth arrest and suppress cell growth. The growth suppression activities of this compound were demonstrated by a downregulation of several genes normally found to be over-expressed in cancers. Microscopic analysis revealed positive monodansylcadaverine (MDC) staining at 8h, indicating possible autophagosomes. TEM analysis revealed that the treated cells were highly vacuolated, thereby suggesting that 14-deoxy-11,12-didehydroandrographolide may cause autophagic morphology in these cells. This morphology may be correlated with the concurrent expression of genes known to affect lysosomal activity, ion transport, protein degradation and vesicle transport. Interestingly, some apoptotic-like bodies were found, and these bodies contained multiple large vacuoles, suggesting that this compound is capable of eliciting a combination of apoptotic and autophagic-like morphological characteristics.
authors.affiliation: Malaysian Institute of Pharmaceuticals and Nutraceuticals, Halaman Bukit Gambir, 11700 Pulau Pinang, Malaysia. tanml@usm.my
authors.forename: Mei Lan
authors.initials: ML
authors.lastname: Tan
authors.forename: Heng Kean
authors.initials: HK
authors.lastname: Tan
authors.forename: Chern Ein
authors.initials: CE
authors.lastname: Oon
authors.forename: Masanori
authors.initials: M
authors.lastname: Kuroyanagi
authors.forename: Tengku Sifzizul Tengku
authors.initials: TS
authors.lastname: Muhammad
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C495626:14-deoxy-11,12-didehydroandrographolide; D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes