Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Anti-Cancer In Vivo and In Vitro Evaluations of Combinations of Cisplatin and Masticadienonic Acid Isolated from Amphypterygium Adstringens

Version 1 : Received: 1 August 2022 / Approved: 3 August 2022 / Online: 3 August 2022 (07:36:50 CEST)

How to cite: Martínez-Vázquez, M. Anti-Cancer In Vivo and In Vitro Evaluations of Combinations of Cisplatin and Masticadienonic Acid Isolated from Amphypterygium Adstringens . Preprints 2022, 2022080074 (doi: 10.20944/preprints202208.0074.v1). Martínez-Vázquez, M. Anti-Cancer In Vivo and In Vitro Evaluations of Combinations of Cisplatin and Masticadienonic Acid Isolated from Amphypterygium Adstringens . Preprints 2022, 2022080074 (doi: 10.20944/preprints202208.0074.v1).

Abstract

Cisplatin (CDDP) is widely used to treat several types of cancer. However, CDDP induces nephrotoxicity. This toxicity could be avoided, applying a lower cisplatin dose; however, it could induce a lesser therapeutic activity. In this paper, we present the cytotoxic activity against prostate human cancer cell line (PC-3) of the combination of CDDP with masticadienonic acid (MDA), a triterpene isolated from Amphypterygium adstringens.The combinations A (half of the IC50), B (IC50) and C (twice IC50 of the compounds) in a radio 1:1 were evaluated. Our results showed that the B and C combinations presented synergism effect. However, B combination showed almost 100% inhibition of cell proliferative activity and increased apoptosis compared with those presented by each compound apart. A pretreatment of MDA 24 h to cells before the CDDP, AMD or B combination administration result in a resistance to the treatments. A xenograft study using PC-3 cells showed that the combination of 47.5 mM/kg (AMD) plus 4 mM/kg (CDDP) administered weekly for 3 weeks reducing the tumor volume in approximately 47 %. However, the combination of 47.5 mg/kg (AMD) plus 2 mg/kg (CDDP) administered every third day for 21 days reduce, approximately 82% of tumor compared with mice no treated.

Keywords

cisplatin; masticadienonic acid; Amphypterygium adstringens; antitumor; xenograft

Subject

CHEMISTRY, Medicinal Chemistry

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