Effect of citral on the cytotoxicity of doxorubicin in human B-lymphoma cells

Abstract

Context: Doxorubicin is a chemotherapy agent used in non-Hodgkin's lymphoma but side effects limit its use. Citral is a mixture of neral and geranial found in essential oils of lemon grass. Objectives: We evaluated the activity of citral, doxorubicin, and combination on cytotoxicity, apoptosis, and anti-proliferative effects using human lymphoma Ramos cells. Materials and methods: Cells were treated with doxorubicin alone or in combination with citral (10, 20, and 40 mM). Cytotoxic and apoptosis studies were done after 24 and 18 h incubations, respectively. Cytotoxic effects of citral on normal human peripheral blood mononuclear cells (PBMCs) were also investigated for its safety. Changes in the expression of BCL-2 family genes were analyzed by quantitative RT-PCR. Results: Citral had cytotoxicity on cells with an IC 50 value of 77.19 ± 4.95 mM. Citral at concentrations of 10, 20, and 40 mM additively increased the cytotoxic and apoptotic effects of doxorubicin, leading to decreased IC 50 (mM) of the drug from 2.50 ± 0.01 to 2.16 ± 0.03, 1.90 ± 0.04, and 1.23 ± 0.04, respectively. Enhanced cytotoxicity was not observed in normal human PBMCs. Citral (40 mM) in combination with doxorubicin (1.5 mM) increased the expression of pro-apoptotic protein BAK but significantly decreased the expression of antiapoptotic protein BCL-XL to 5.26-fold compared with doxorubicin-treated cells. It did not change the anti-proliferative activity of drug. Discussion and conclusion: Citral potentiated cytotoxicity of doxorubicin by increasing apoptotic effects. We conclude that citral may have beneficial effects in patients with B cell lymphoma treated with chemotherapy.

Phytochemical Profile and Evaluation of the Biological Activities of Essential Oils Derived from the Greek Aromatic Plant Species Ocimum basilicum, Mentha spicata, Pimpinella anisum and Fortunella margarita

“…Consequently, there is a need for novel agents with specific toxicity against cancer cells that will enhance the efficacy of standard treatment and may also alleviate any undesired cytotoxic side effects. Quite interestingly, studies have shown synergistic effects of conventional chemotherapeutic drugs when administered together with specific essential oils or some of their major components, responsible for exerting such effects [5,6,7,8]. This further supports the notion that nutritional intervention with natural phytochemicals, such as essential oils, may be very advantageous in enhancing the therapeutic potential of any existing therapy (e.g., chemotherapy) and furthermore diminish any adverse side effects [9].…”

Co-delivery of Doxorubicin and Curcumin with Polypeptide Nanocarrier for Synergistic Lymphoma Therapy

“…These results confirmed the involvement of mitochondrial apoptosis pathway induced by DNA damage in the Bcl-2 family. The anti-apoptotic protein represented by Bcl-2 and the pro-apoptotic protein represented by Bax affect the release of cytochrome c (CytC) on the mitochondrial membrane, initiate the caspase3 apoptotic pathway signaling, and promote the apoptosis when the ratio of Bax to Bcl-2 is high 7,20,23,[31][32][33][34] . Moreover, the L-DOX + CUR group showed a stronger induction of apoptosis than the other groups.…”

Endophytic Streptomyces sp. LRE541 isolated from Lilium davidii var. Unicolor Cotton as a Cell Factory for Antimicrobials and Anticarcinogens with Inducing Apoptosis and Cell Cycle Arrest Properties

“…Based on the UHPLC-MS/MS analysis, the EtOAc extract was detected to contain thirty-nine compounds testi ed to exhibit various antitumor activities and cytotoxicity, besides, sixteen compounds proved to be antagonistic against diverse microorganisms. For example, ferulic acid, relative ratio of 15.3965% in the ESI (−) mode, as a new broblast growth factor receptor 1 (FGFR1) inhibitor, could inhibit the melanoma growth and angiogenesis using a melanoma model in vivo (60); similarly, 4-Hydroxybenzylalcohol, a promising anti-angiogenic agent, suppressed the vascularization and growth of newly developing CT26.WT tumors in vivo (61); while formononetin and catechin suppressed MCF-7 proliferation through blocking the cell cycle arrest or inducing apoptosis, respectively (62,63); citral in combination with doxorubicin, and glycocholic acid with epirubicin, can dramatically increase the chemosensitivity of doxorubicin in human lymphoma Ramos cells, epirubicin in Caco-2 cells, respectively (64,65). Sorbic acid and Lauric acid with relative ratios of 14.9% and 1.2% in the ESI (+)/(−) modes, respectively, have broadspectrum antagonistic activities against most of the Gram-positive, Gram-negative pathogens and fungi (66,67).…”