In Vivo Antitumoral Effects of Linseed Oil and Its Combination With Doxorubicin

Abstract

Linseed oil (LO) is known for its exceptional nutritional value due to the high content of alpha-linolenic acid (ALA), an essential omega-3 polyunsaturated fatty acid; its anticarcinogenic effect has been established in several experimental and epidemiological studies. As an adjuvant of chemotherapeutic agents, LO and other ALA-rich vegetable oils have been studied in only a handful of studies at the experimental level. However, the efficacy of antitumoral therapy using doxorubicin (Dox) in combination with ALA and ALA-rich substrates has not yet been investigated. In this work, the antitumor activity of LO in a wide dose range was studied with monotherapy and combined with Dox in animal models with Pliss lymphosarcoma (PLS) and Lewis lung adenocarcinoma (LLC). It was founded the daily oral administration of LO (1, 3, and 10 ml per 1 kg) to rats (PLS) and 6 ml/kg to mice (LLC) for 11–12 days from 7 days after subcutaneous transplantation of tumors has a stable statistically significant effect on the dynamics of tumor growth, reducing the intensity of tumor growth and increasing the frequency of complete tumor regressions (CR) compared with the control. LO showed high antimetastatic activity in the LLC model. Furthermore, LO at a dose of 3 ml/kg potentiates the antitumor effect of Dox in the PLS model, reducing the volume of tumors at the end of treatment by 2.0 times (p = 0.013), the value of the tumor growth index by 1.6 times (p < 0.03) and increasing the frequency of CR 60 days after the start of therapy by 3.5 times (p = 0.019) compared with the use of Dox alone. The combination of Dox and LO or fish oil allows growing efficiency therapy of LLC in comparison with Dox alone, increasing the frequency of CR to 73.68% and 94.4%, respectively, and reducing the frequency of metastasis to zero.

Chitosan-loaded piperlongumine nanoparticles and kaempferol enhance the anti-cancer action of doxorubicin in targeting of Ehrlich solid adenocarcinoma: in vivo and in silico modeling study

“…One of the most commonly used chemotherapeutic agents for treating breast cancer and other solid tumors is DOX. The effectiveness of a combination treatment between DOX and natural agents was reported against cancer [ 23 ].…”

Adjuvant composite cold atmospheric plasma therapy increases antitumoral effect of doxorubicin hydrochloride

“…injection on the 5th day after tumor transplantation. The choice of the doxorubicin dose in our study was based on previous experiments conducted in a similar experimental model with rats, which demonstrated relative safety at a single dose of 5 mg/kg ( 48 , 49 ).…”

The Antitumor Effects of α-Linolenic Acid

“…Doxorubicin (Dox) is a broad-spectrum antibiotic that can exert antitumor effects by increasing the levels of ROS in cells. Oleg Shadyro et al [ 94 ] reported that Dox combined with FO can not only reduce the intensity and volume of Pliss lymphosarcoma and Lewis lung adenocarcinoma but also inhibit Lewis lung adenocarcinoma metastasis. In addition, because PUFAs are components of the cell membrane, ALA may be used as a functional material for small molecule modification via coupling with antitumor drugs [ 95 ].…”