New Lupane Derived Compounds with Pro-Apoptotic Activity in Cancer Cells:  Synthesis and Structure−Activity Relationships

Šarek, Jan; Klinot, J.; Džubák, Petr; Klinotová, Eva; Nosková, Věra; Křeček, Václav; Korinkova, Gabriela; Thomson, Jean Oliver; Janošťáková, Anna; Wang, Shudong; Parsons, Simon; Fischer, Peter M.; Zhelev, Nikolai; Hajdúch, Marián

doi:10.1021/jm020854p

Cited by 84 publications

(56 citation statements)

References 22 publications

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“…In a previous study, we demonstrated that BA was cytotoxic to an MDR erythroleukemia cell line that overexpresses ABCB1 (24). The antitumoral effect of BA was also observed in tumor cell lines with defective or mutated p53 (13,16), as well as in cell lines that acquire resistance to cytotoxic drugs (16,18). In this study, we investigated the effect of BA on Ma-104, a non-tumoral renal cell line that constitutively expresses P-gp/ABCB1 and MRP1/ABCC1 (20).…”

Section: Resultsmentioning

confidence: 89%

“…1, BA decreased the viability of Ma-104 cells in a dose-dependent manner. High concentrations of BA were required to substantially decrease the viability of Ma-104 cells after 48 h of treatment; however, at 10 μg/ml, a concentration at which BA is highly cytotoxic (14)(15)(16)(17)(18)(19), the effect of BA on Ma-104 was very low. Thus, to avoid the possible interference of cell death mechanisms on the measurement of ABCB1 and ABCC1 activities, subsequent experiments were performed using 10 μg/ml of BA.…”

Section: Resultsmentioning

confidence: 99%

“…Interest in this compound increased with the observation of its in vitro and in vivo activity against melanomas and tumors of neuro-ectodermal origin (12)(13)(14). Later, it was demonstrated that BA is also active in other types of tumors, including colon and prostate (15), lung, ovarian, cervical (16), leukemia (17), liver (18), and head and neck (19) carcinomas. Previous research by our group revealed that BA was cytotoxic to an MDR erythroleukemic cell line overexpressing P-glycoprotein, even in the absence of MDR modulators (20).…”

Section: Introductionmentioning

confidence: 99%

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Betulinic acid does not modulate the activity of P-gp/ABCB1 or MRP1/ABCC1 in a non-tumoral renal cell line: Possible utility in multidrug resistance cancer chemotherapy

Delou

Capella²,

Gattass³

2009

Mol Med Rep

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Abstract. Multidrug resistance (MDR) is a multifactorial phenomenon considered to be the main cause of failure in cancer chemotherapy. One of the underlying mechanisms of MDR is the overexpression of membrane transporter proteins, such as P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated protein 1 (MRP1/ABCC1). As these proteins are also expressed in normal tissues, considerable attention has been dedicated to the search for cytotoxic drugs that are not substrates for these proteins. This study investigated the effects of betulinic acid (BA) on the activity of ABCB1 and ABCC1 in Ma-104, a non-tumoral renal cell line constitutively expressing both proteins. The results indicated that concentrations of BA with low cytotoxicity to Ma-104 did not alter the activity of ABCB1 or ABCC1, nor did BA interfere with the accumulation of a classic chemotherapeutic, methotrexate. This suggests it would also be a good choice for use in drug cocktails. The lack of effect of BA on ABCB1 and ABCC1, as well as its antitumoral properties, suggest that this triterpene is a viable chemotherapeutic agent for MDR tumors.

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Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Betulinic acid does not modulate the activity of P-gp/ABCB1 or MRP1/ABCC1 in a non-tumoral renal cell line: Possible utility in multidrug resistance cancer chemotherapy

Delou

Capella²,

Gattass³

2009

Mol Med Rep

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“…for biological activity and found that they demonstrated significant cytotoxic 172 activity under in vitro conditions (Table 2). Roseotoxins also have strong anti-inflammatory activity 173 (Table 3) in vitro.…”

Section: Biological Activities Of Cyclic Peptidesmentioning

confidence: 99%

Nonribosomal cyclic peptides: specific markers of fungal infections

Jegorov¹,

Hajdúch

Šulc

et al. 2006

J. Mass Spectrom.

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Some cyclic peptides and depsipeptides are synthesized in microorganisms by large multienzymes called nonribosomal peptide synthetases. The structures of peptide products originating in this way are complex and diverse and are microorganism-specific. This work proposes the use of fungal cyclic peptides and depsipeptides as extremely specific markers of fungal infections. Since a reliable molecular tool for diagnosing fungal infections at an early stage is still missing, we present mass spectrometry as a new, modern, broadband (with respect to fungal strain) and specific tool for clinical mycologists. More than 40 different fungal species can be rapidly characterized according to specific families of cyclic peptides, and in some cases, a particular fungal strain can be identified on the basis of its cyclopeptide profile. This paper is also aimed at initiating discussion on the biological role of these secondary metabolites, especially of those synthesized by medically important strains. Proven cytotoxic, anti-inflammatory or immunosuppressive activities of some cyclic peptides indicate that these molecules may contribute to the synergistic array of fungal virulence factors and support microbial invasion during fungal infection. In addition to an overview on recent mass spectrometric protocols for cyclic peptide sequencing, the structures of new peptides from Paecilomyces and Pseudallescheria are presented.

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“…1), including medulloblastoma, glioblastoma, Ewing's sarcoma (23), neuroblastoma (24) and leukemia (25). BA has been demonstrated to be effective on drug-resistant and -sensitive tumor cell lines, indicating its significant therapeutic benefit to chemotherapy-resistant patients with cancer (26). In addition, the impact of BA on hedgehog signalling was determined, which has been implicated in rhabdomyosarcoma development (27).…”

Section: Introductionmentioning

confidence: 99%

Effect of overexpression of HOX genes on its invasive tendency in cerebral glioma

Guo

Shao²,

Chen

et al. 2015

Oncology Letters

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Abstract. Transcription factors encoded by HOX genes are vital in the determination of cell fate and identity during embryonic development. In certain malignancies, HOX genes also behave as oncogenes. The present study demonstrated suppression of the invasive tendency of glioblastoma multiforme U-118 and U-138 cells by the introduction of the antisense fragments of HOXA6 and B13 genes using electroporation. The invasion index indicated 79 and 72% reductions in the invasive ability of antisense HOXA6 and B13, respectively. No significant differences in the invasive index of the parental and mock cells of each HOX gene were observed (invasive index, 0.75-0.91; P=0.05). A reduction in invasion tendency was also observed following betulinic acid (BA) treatment: The results from the matrigel assay analysis clearly demonstrated a significant inhibition in the invasive behaviour of U-118 and U-138 cell lines from day 15 following BA treatment, with a maximum effect on day 30. The invasion index demonstrated 62 and 65% reductions in invasion ability in the U-118 and U-138 cell lines, respectively. The suppression of HOXC6 and B13 expression by the introduction of the corresponding antisense fragments in addition to BA reduced invasion tendency in U-118 and U-138 cell lines. The mechanism underlying the association between the HOX gene and invasive behavior in glioma cells is yet to be understood. However, the anti-invasive behavior of BA may aid understanding of the mechanism in future studies.

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New Lupane Derived Compounds with Pro-Apoptotic Activity in Cancer Cells: Synthesis and Structure−Activity Relationships

Cited by 84 publications

References 22 publications

Betulinic acid does not modulate the activity of P-gp/ABCB1 or MRP1/ABCC1 in a non-tumoral renal cell line: Possible utility in multidrug resistance cancer chemotherapy

Betulinic acid does not modulate the activity of P-gp/ABCB1 or MRP1/ABCC1 in a non-tumoral renal cell line: Possible utility in multidrug resistance cancer chemotherapy

Nonribosomal cyclic peptides: specific markers of fungal infections

Effect of overexpression of HOX genes on its invasive tendency in cerebral glioma

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