9-Deoxopodophyllotoxin derivatives as anti-cancer agents

Subrahmanyam, D.; Renuka, B.; Kumar, Girijesh; Vandana, V.; Deevi, Danvanthri S.

doi:10.1016/s0960-894x(99)00347-9

Cited by 21 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DPT, an analogue of podophyllotoxin, is a naturally occurring microtubule-depolymerizing flavolignan [ 32 ]. It has been reported that DPT displays anti-proliferative, anti-tumor, anti-inflammatory, and anti-viral activities [ 22 , 33 ]. Many studies reported that DPT induces cell cycle arrest at the G2/M phase by inhibiting tubulin polymerization.…”

Section: Discussionmentioning

confidence: 99%

“…Deoxypodophyllotoxin (DPT), isolated from Anthriscus sylvestris , is a naturally occurring flavolignan in medicinal herb plants. DPT has been shown to have potential anti-proliferative and anti-tumor activities in various cancer cell lines as well as anti-inflammatory and anti-viral activity [ 22 ]. Despite these findings, the details of the cellular and molecular mechanisms underlying the DPT-mediated cell death are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial ROS activates ERK/autophagy pathway as a protected mechanism against deoxypodophyllotoxin-induced apoptosis

Kim

Park

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Deoxypodophyllotoxin (DPT) is a naturally occurring flavolignan isolated from Anthriscus sylvestris. Recently, it has been reported that DPT inhibits tubulin polymerization and induces G2/M cell cycle arrest followed by apoptosis through multiple cellular processes. Despite these findings, details regarding the cellular and molecular mechanisms underlying the DPT-mediated cell death have been poorly understood. To define a mechanism of DPT-mediated cell death response, we examined whether DPT activates signaling pathways for autophagy and apoptosis. We demonstrated that DPT inhibited cell viability and induced apoptosis in prostate cancer cell lines, as evidenced by a mitochondrial membrane potential and expression of apoptosis-related proteins. Reactive oxygen species (ROS), primarily generated from the mitochondria, play an important role in various cellular responses, such as apoptosis and autophagy. DPT significantly triggered mitochondrial ROS, which were detected by MitoSOX, a selective fluorescent dye of mitochondria-derived ROS. Furthermore, DPT induced autophagy through an up-regulation of autophagic biomarkers, including a conversion of microtubule-associated protein 1 light chain 3 - I (LC3-I) into LC3-II and a formation of acidic vesicular organelles. Moreover, mitochondrial ROS promoted AKT-independent autophagy and ERK signaling. The inhibition of autophagy with 3-methyladenine or LC3 knockdown enhanced DPT-induced apoptosis, suggesting that an autophagy plays a protective role in cell survival against apoptotic prostate cancer cells. Additionally, the results from an in vivo xenograft model confirmed that DPT inhibited tumor growth by regulating the apoptosis- and autophagy-related proteins.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial ROS activates ERK/autophagy pathway as a protected mechanism against deoxypodophyllotoxin-induced apoptosis

Kim

Park

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…Greenwald et al, 1999 reported oncolytic activity of a series of water soluble acyl derivatives of PEG conjugated podophyllotoxin. Several 9-deoxy-9-substituted podophyllotoxin derivatives possess good anticancer activity against ovarian, renal and lung cancer cell lines (Subrahmanyam et al, 1999).…”

Section: Pharmacology and Mode Of Actionmentioning

confidence: 99%

Untitled

2000

View full text Add to dashboard Cite

Podophyllum hexandrum Royle of family Berberidaceae is an endangered medicinal plant. Rhizome ofP.hexandrum contains several lignans which posses antitumor activity. Podphyllotoxin is the most active cytotoxic natural product. It is used as starting compound for the synthesis of anticancer drug etoposide and teniposide. Podophyllotoxin acts as an inhibitor of microtubule assembly. These drugs are used for lung cancer, testicular cancer, neuroblastoma, hepatoma and other tumors. Besides this, it also shows antiviral activities by interfering with some critical viral processes. Availabilityof podophyllotoxin from plants has its limitations because of its intense collection from nature and lack of organized cultivation. The chemical synthesis of podophyllotoxin is considered to be very complicated as yet. The use of biotechnological approaches for the production of podophyllotoxin using cell cultures, organ cultures, and biotransformation route or by manipulating biosynthetic pathway proves to be an attractive alternative for production of podophyllotoxin. The present paper discusses the current status of research, limitations and future prospects for theproduction of podophyllotoxinin vitro.

show abstract

“…Furthermore, it is able to perform alkenylation reactions on lactols (presumably by reacting with the small amount of carbonyl present in the equilibrium mixture) to afford hydroxy-substituted enone products (eq 10). 13 The possibility also exists for the hydroxy-enone products to undergo an intramolecular Michael addition to form new heterocycles, such as the tetrahydrofuran formation on the podophyllotoxin-derived example shown below. (12) In addition to alkenylations on preformed carbonyl species, acetylmethylenetriphenylphosphorane is capable of forming enone products from a variety of alternative starting materials.…”

Section: First Updatementioning

confidence: 99%