Antiproliferative and Cytotoxic Properties of Propynoyl Betulin Derivatives against Human Ovarian Cancer Cells: In Vitro Studies

被引：4

作者：

Chodurek, Ewa ^{[1
]}

Orchel, Arkadiusz ^{[1
]}

Gwiazdon, Pawel ^{[1
]}

Kaps, Anna ^{[1
]}

Paduszynski, Piotr ^{[1
]}

Jaworska-Kik, Marzena ^{[1
]}

Chrobak, Elwira ^{[2
]}

Bebenek, Ewa ^{[2
]}

Boryczka, Stanislaw ^{[2
]}

Kasperczyk, Janusz ^{[1
]}

Nakayama, Kentaro

机构：

[1] Med Univ Silesia, Fac Pharmaceut Sci Sosnowiec, Dept Biopharm, 8 Jednosci Str, PL-41208 Sosnowiec, Poland

[2] Med Univ Silesia, Fac Pharmaceut Sci Sosnowiec, Dept Organ Chem, 4 Jagiellonska Str, PL-41200 Sosnowiec, Poland

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 22期

关键词：

ovarian cancer; betulin derivatives; cytotoxicity; regulated cell death; CYTOCHROME-C RELEASE; APOPTOSIS; ACID; NECROSIS; PHOSPHATE; DEATH; 28-O-PROPYNOYLBETULIN; PROLIFERATION; ACTIVATION; CASPASES;

D O I：

10.3390/ijms242216487

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Due to the incidence of ovarian cancer (OC) and the limitations of available therapeutic strategies, it is necessary to search for novel therapeutic solutions. The aim of this study was to evaluate the cytotoxic effect of betulin 1 and its propynoyl derivatives 2-6 against ovarian cancer cells (SK-OV-3, OVCAR-3) and normal myofibroblasts (18Co). Paclitaxel was used as the reference compound. The propynoyl derivatives 2-6 exhibited stronger antiproliferative and cytotoxic activities compared to betulin 1. In both ovarian cancer cell lines, the most potent compound was 28-propynoylbetulin 2. In the case of compound 2, the calculated IC50 values were 0.2 mu M for the SK-OV-3 cells and 0.19 mu M for the OVCAR-3 cells. Under the same culture conditions, the calculated IC50 values for compound 6 were 0.26 mu M and 0.59 mu M, respectively. It was observed that cells treated with compounds 2 and 6 caused a decrease in the potential of the mitochondrial membrane and a significant change in cell morphology. Betulin 1, a diol from the group of pentacyclic triterpenes, has a confirmed wide spectrum of biological effects, including a significant anticancer effect. It is characterized by low bioavailability, which can be improved by introducing changes to its structure. The results showed that chemical modifications of betulin 1 only at position C-28 with the propynoyl group (compound 2) and additionally at position C-3 with the phosphate group (compound 3) or at C-29 with the phosphonate group (compound 6) allowed us to obtain compounds with greater cytotoxic activity than their parent compounds, which could be used to develop novel therapeutic systems effective in the treatment of ovarian cancer.

引用

页数：18

共 64 条

[1] Understanding and Targeting Apoptotic Pathways in Ovarian Cancer [J].

Al-Alem, Linah F. ;

Baker, Andrew T. ;

Pandya, Unnati M. ;

Eisenhauer, Eric L. ;

Rueda, Bo R. .

CANCERS, 2019, 11 (11)

[2] Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets [J].

Alatise, Kharimat Lora ;

Gardner, Samantha ;

Alexander-Bryant, Angela .

CANCERS, 2022, 14 (24)

[3] Betulin and its derivatives as novel compounds with different pharmacological effects [J].

Amiri, Shayan ;

Dastghaib, Sanaz ;

Ahmadi, Mazaher ;

Mehrbod, Parvaneh ;

Khadem, Forough ;

Behrouj, Hamid ;

Aghanoori, Mohamad-Reza ;

Machaj, Filip ;

Ghamsari, Mahdi ;

Rosik, Jakub ;

Hudecki, Andrzej ;

Afkhami, Abbas ;

Hashemi, Mohammad ;

Los, Marek J. ;

Mokarram, Pooneh ;

Madrakian, Tayyebeh ;

Ghavami, Saeid .

BIOTECHNOLOGY ADVANCES, 2020, 38

[4] Apoptosis Induced by (+)-Betulin Through NF-κB Inhibition in MDA-MB-231 Breast Cancer Cells [J].

Anaya-Eugenio, Gerardo D. ;

Eggers, Nicole A. ;

Ren, Yulin ;

Rivera-Chavez, Jose ;

Kinghorn, A. Douglas ;

de Blanco, Esperanza J. Carcache .

ANTICANCER RESEARCH, 2020, 40 (12) :6637-6647

[5] Betulin: a natural product with promising anticancer activity against colorectal cancer cells [J].

Bebenek, Ewa ;

Chrobak, Elwira ;

Piechowska, Agnieszka ;

Gluszek, Stanislaw ;

Boryczka, Stanislaw .

MEDICAL STUDIES-STUDIA MEDYCZNE, 2020, 36 (04) :297-301

[6] Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology [J].

Bonora, Massimo ;

Patergnani, Simone ;

Ramaccini, Daniela ;

Morciano, Giampaolo ;

Pedriali, Gaia ;

Kahsay, Asrat Endrias ;

Bouhamida, Esmaa ;

Giorgi, Carlotta ;

Wieckowski, Mariusz R. ;

Pinton, Paolo .

BIOMOLECULES, 2020, 10 (07) :1-25

[7] Synthesis, Structure and Cytotoxic Activity of New Acetylenic Derivatives of Betulin [J].

Boryczka, Stanislaw ;

Bebenek, Ewa ;

Wietrzyk, Joanna ;

Kempinska, Katarzyna ;

Jastrzebska, Maria ;

Kusz, Joachim ;

Nowak, Maria .

MOLECULES, 2013, 18 (04) :4526-4543

[8] Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting [J].

Bradbury, Alice ;

O'Donnell, Rachel ;

Drew, Yvette ;

Curtin, Nicola J. ;

Saha, Sweta Sharma .

CANCERS, 2020, 12 (07) :1-17

[9] The ever-increasing importance of cancer as a leading cause of premature death worldwide [J].

Bray, Freddie ;

Laversanne, Mathieu ;

Weiderpass, Elisabete ;

Soerjomataram, Isabelle .

CANCER, 2021, 127 (16) :3029-3030

[10] Autophagy, Apoptosis, Mitoptosis and Necrosis: Interdependence Between Those Pathways and Effects on Cancer [J].

Chaabane, Wiem ;

User, Sirma D. ;

El-Gazzah, Mohamed ;

Jaksik, Roman ;

Sajjadi, Elaheh ;

Rzeszowska-Wolny, Joanna ;

Los, Marek J. .

ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS, 2013, 61 (01) :43-58

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