Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents

Subrahmanyam, D.; Renuka, B.; Rao, Chinthalapally V.; Sagar, P.; Deevi, Dhanvanthri S.; Babu, J. Moses; Vyas, K.

doi:10.1016/s0960-894x(98)00232-7

Cited by 63 publications

(21 citation statements)

References 15 publications

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“…Podophyllotoxin, it is effective in the treatment of Wilms tumours, different types of genital tumors (carcinoma verrucosus, for example) and in non-Hodgkin and other lymphomas (Ayres and Loike, 1990) and lung cancer (Utsugi et al, 1996;Subrahmanyam et al, 1998). Three semisynthetic derivatives of podophyllotoxin, etoposide, teniposide and etopophos, were widely used as anticancer drugs and show good clinical effects against several types of neoplasms including testicular and small-cell lung cancers, lymphoma, leukaemia, Kaposi's sarcoma, etc (Ayres and Loike, 1990).…”

Section: Discussionmentioning

confidence: 99%

Induction of Cell Cycle Arrest and Apoptosis by Ormenis Eriolepis a Morrocan Endemic Plant in Various Human Cancer Cell Lines

Belayachi¹,

Aceves-Luquero²,

Merghoub³

et al. 2017

Afr J Tradit Complement Altern Med

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Background: Ormenis eriolepis Coss (Asteraceae) is an endemic Moroccan subspecies, traditionally named "Hellala" or "Fergoga". It's usually used for its hypoglycemic effect as well as for the treatment of stomacal pain. As far as we know, there is no scientific exploration of anti tumoral activity of Ormenis eriolepis extracts. Materials and Methods:In this regard, we performed a screening of organic extracts and fractions in a panel of both hematological and solid cancer cell lines, to evaluate the potential in vitro anti tumoral activity and to elucidate the respective mechanisms that may be responsible for growth arrest and cell death induction. The plant was extracted using organic solvents, and four different extracts were screened on Jurkat, Jeko-1, TK-6, LN229, SW620, U2OS, PC-3 and NIH3T3 cells. Results: Cell viability assays revealed that, the IC50 values were (11,63±5,37µg/ml) for Jurkat, (13,33±1,67µg/ml) for Jeko-1, (41,67±1,98µg/ml) for LN229 and (19,31±4,88µg/ml) for PC-3 cells upon treatment with Oe-DF and Oe-HE respectively. Both the fraction and extract exhibited no effects on TK6 and NIH3T3. Cytometry analysis accompanied by DNA damage signaling protein levels monitoring (p-H2A.X), showed that both the Dichloromethane Fraction and Hexanic extract induce DNA double stranded breaks (DSBs) accompanied by cell cycle arrest in G1 (Jurkat, Jeko -1 and LN22) and G2/M (PC-3) phases which is agreed with the caspase activity observed. Additional experiments with selective inhibitors of stress and survival pathways (JNK, MAPK, Rho, p53, and JAK3) indicated that none of these pathways was significantly involved in apoptosis induction. The bioactive compound analysis by CG/MS indicated that the major compounds in Oe-DF were: Linoleic Acid (15,89%), Podophyllotoxin (17,89%) and Quercetin (22,95%). For Oe-HE the major molecules were: Linoleic Acid (9,76%), α-curcumene (7,07%), α-bisabolol (5,49%), Campesterol (4,41%), Stigmasterol (14,08%) and β-sitosterol (7,49%). Conclusion: Our data suggest that bioactive compounds present in Ormenis eriolepis show significant anti proliferative activity inducing cell cycle arrest and cell death operating through apoptosis pathway.

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Section: Discussionmentioning

confidence: 99%

Induction of Cell Cycle Arrest and Apoptosis by Ormenis Eriolepis a Morrocan Endemic Plant in Various Human Cancer Cell Lines

Belayachi¹,

Aceves-Luquero²,

Merghoub³

et al. 2017

Afr J Tradit Complement Altern Med

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“…1), and the D-ring lactone opened derivative (i.e., 4 0 -demethylepipodophyllic acid) was produced, which was the first report for the production of 4 0 -demethylepipodophyllic acid by DMEP biotransformation [25]. 4 0 -Demethylepipodophyllic acid (DMEPA) is the water-solubility increased derivative of DMEP, and its derivatives were reported to show impressive activity against most of the colon and breast cancer cell lines [26].…”

Section: Introductionmentioning

confidence: 99%

A novel biotransformation process of 4′-demethylepipodophyllotoxin to 4′-demethylepipodophyllic acid by Bacillus fusiformis CICC 20463, Part II: process optimization

Tang

Zhong

2009

Bioprocess Biosyst Eng

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This work optimized the novel biotransformation process of 4'-demethylepipodophyllotoxin (DMEP) into 4'-demethylepipodophyllic acid (DMEPA) by Bacillus fusiformis CICC 20463. Firstly, the biotransformation process was significantly affected by medium composition. 5 g/L of yeast extract and 10 g/L of peptone were optimal for DMEPA production (i.e., 2.81 + or - 0.21 mg/L), while not beneficial for the cell growth of B. fusiformis. This indicated that the biosynthesis of DMEPA was not corresponded well to the cell growth of B. fusiformis. 40 g/L of sucrose was optimal for DMEPA production (i.e., 2.94 + or - 0.17 mg/L), and 3 g/L of NaCl was the best for DMEPA production (i.e., 4.10 + or - 0.18 mg/L). Secondly, the production of DMEPA was significantly enhanced by the control of substrate concentration and culture pH. 100 mg/L of substrate was optimal for DMEPA production (i.e., 6.47 + or - 0.35 mg/L), and DMEPA concentration was enhanced to 38.78 mg/L by controlling culture pH at 9.0 in the stirred-tank bioreactors. The fundamental information obtained in this study provides a simple and efficient way to produce DMEPA by biotransformation.

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“…According to the time course of podophyllotoxin biotransformation process, it was concluded that podophyllotoxin was converted into picropodophyllotoxin (2), and both of them can be transformed into podophyllic acid (3) further by P. aeruginosa (Fig. 5), which showed impressive in vitro activity against ovarian and melanoma cell lines [23].…”

Section: Time Course Of Podophyllotoxin Biotransformation Process By mentioning

confidence: 99%

“…Podophyllic acid showed impressive in vitro activity against ovarian and melanoma cell lines [23], furthermore, the biotransformation product could be used as a leading compound to synthesize its hydrazide derivates with stronger anti-cancer and antioxidative activity [24,25]. It has been reported that podophyllic acid could be prepared from podophyllotoxin by chemical transformation [26,27].…”

Section: Introductionmentioning

confidence: 99%

Novel biotransformation process of podophyllotoxin to produce podophyllic acid and picropodophyllotoxin by Pseudomonas aeruginosa CCTCC AB93066. Part I: Process development

Tang

Zhong

2008

Bioprocess Biosyst Eng

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A novel biotransformation process of podophyllotoxin (1) to produce picropodophyllotoxin (2) and podophyllic acid (3) was developed in this work. Eight bacteria which could modify the structure of podophyllotoxin were screened out from the tested fourteen bacteria. The highest conversion of podophyllotoxin (i.e., 70.2 +/- 8.0%) was obtained when Pseudomonas aeruginosa CCTCC AB93066 was used as biocatalyst, so P. aeruginosa was selected as a typical biocatalyst in the following study. Product (2) and (3) were separated through D312 macroporous resin and sephadex LH-20 gel column chromatograph. On the basis of (1)H NMR, (13)C NMR, ESI-MS and Elemental Analysis, product (2) and (3) were identified as picropodophyllotoxin (2) and podophyllic acid (3), respectively. This suggested the site-specific isomerization and hydrolization of podophyllotoxin occurred during its biotransformation process by P. aeruginosa. For the first time, podophyllotoxin was biotransformed into its hydrolytic derivate (i.e., podophyllic acid).

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Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents

Cited by 63 publications

References 15 publications

Induction of Cell Cycle Arrest and Apoptosis by Ormenis Eriolepis a Morrocan Endemic Plant in Various Human Cancer Cell Lines

Induction of Cell Cycle Arrest and Apoptosis by Ormenis Eriolepis a Morrocan Endemic Plant in Various Human Cancer Cell Lines

A novel biotransformation process of 4′-demethylepipodophyllotoxin to 4′-demethylepipodophyllic acid by Bacillus fusiformis CICC 20463, Part II: process optimization

Novel biotransformation process of podophyllotoxin to produce podophyllic acid and picropodophyllotoxin by Pseudomonas aeruginosa CCTCC AB93066. Part I: Process development

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