Oxidovanadium(IV) complexes with chrysin and silibinin: anticancer activity and mechanisms of action in a human colon adenocarcinoma model

Abstract

Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal antitumor agents in combination to its low toxicity. On the other hand, flavonoids are a wide family of polyphenolic compounds synthesized by plants that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, a exhaustive study of the mechanisms of action of two oxidovanadium(IV) complexes with the flavonoids: silibinin Na₂[VO(silibinin)₂2]·6H₂O (VOsil) and chrysin [VO(chrysin)₂EtOH]₂(VOchrys) on human colon adenocarcinoma derived cell line HT-29. The complexes inhibited the cell viability of colon adenocarcinoma cells in a dose dependent manner with a greater potency than that the free ligands and free metal, demonstrating the benefit of complexation. The decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of both complexes. Besides, VOchrys caused cell cycle arrest in G2/M phase while VOsil activated caspase 3 and triggering the cells directly to apoptosis. Moreover, VOsil diminished the NF-kB activation via increasing the sensitivity of cells to apoptosis. On the other hand, VOsil inhibited the topoisomerase IB activity concluding that this is important target involved in the anticancer vanadium effects. As a whole, the results presented herein demonstrate that VOsil has a stronger deleterious action than VOchrys on HT-29 cells, whereby suggesting that Vosil is the potentially best candidate for future use in alternative anti-tumor treatments.

Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles

“…However, chemical modification of chrysin has become the focus of research attention in order to resolve the abovementioned problem. 21 An oxidovanadium complex with chrysin was reported to improve chemotherapy in a colon adenocarcinoma model 22 and in an osteosarcoma model. 23 Furthermore, methoxy poly(ethylene glycol) (mPEG)-chrysin conjugates were reported to increase the encapsulation efficacy of doxorubicin and to enhance its anticancer effects.…”

Inhibitory effects of silibinin on proliferation and lung metastasis of human high metastasis cell line of salivary gland adenoid cystic carcinoma via autophagy induction

“…Recent studies have found that SIL has strong antitumor activities toward a variety of epithelium-derived tumors, such as prostate,2 colon,1 bladder,13 breast,14 ovarian,15 and lung cancers 3,4. This study analyzed the impacts of SIL on the proliferation of ACC-M cells, and the results revealed that SIL could inhibit the proliferation of ACC-M cells in time- and dose-dependent manner, particularly when treated with 160 µg/mL of SIL for 72 hours, the inhibition rate of 93% suggested that SIL had significant inhibitory activities toward ACC.…”

“…Recent studies have found that SIL has strong antitumor activities toward a variety of epithelium-derived tumors such as colon,1 prostate,2 or lung cancer,3,4 and induction of tumor cell autophagy might be one of the mechanisms. Autophagy is a stress reaction of cells under starvation, hypoxia, and other internal or external environmental pressure conditions.…”

New Insights toward Colorectal Cancer Chemotherapy Using Natural Bioactive Compounds

“…Chrysin vanadate complex reduced to 56% the HT-29 cell survival vs. 88% in the case of cisplatin. This chrysin potentiating effect may be due to a reduction in GSH levels, one of the most important antioxidant defenses in mammals (León et al, 2015). In order to avoid gastrointestinal damage in preclinical trials, different vanadium complexes have been generated with flavonoids (Evangelou, 2002).…”

“…In this combination, chrysin induces cell cycle arrest in G 2 /M transition, while silibinin induces apoptosis due to caspases activation and NF-κB inhibition (León et al, 2015). …”