Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming; Wang, Yujiong

doi:10.3390/cancers4041318

Cited by 28 publications

(22 citation statements)

References 37 publications

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“…The biocompatibility of AZI-liposomes (CL-3, PGL-2 and DPGL-2) was investigated in vitro to determine the possible cytotoxic effects of the liposome constituents and AZI toward human cervical cells (HeLa cells). It was reported that AZI can synergistically enhance the antiproliferative activity of vincristine in cancer cells 54. Furthermore, recent findings demonstrated that free AZI was cytotoxic to human fibroblasts at a concentration of 16 µg/ml (49% viability) and human keratinocytes at 64 µg AZI/ml (55% viability), while entrapment of AZI in liposomes significantly decreased skin cell cytotoxicity 17…”

Section: Resultsmentioning

confidence: 98%

<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

Vanić¹,

Rukavina²,

Manner³

et al. 2019

IJN

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Background Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms. Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC 50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.

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Section: Resultsmentioning

confidence: 98%

<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

Vanić¹,

Rukavina²,

Manner³

et al. 2019

IJN

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“…A CDI value <1, =1 or >1 indicates that the drugs are synergistic, additive or antagonistic, respectively. A CDI value less than 0.7 indicates that the drugs are significantly synergistic [46,47].…”

Section: Methodsmentioning

confidence: 99%

The Synergistic Biologic Activity of Oleanolic and Ursolic Acids in Complex with Hydroxypropyl-γ-Cyclodextrin

et al. 2014

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Oleanolic and ursolic acids are natural triterpenic compounds with pentacyclic cholesterol-like structures which gives them very low water solubility, a significant disadvantage in terms of bioavailability. We previously reported the synthesis of inclusion complexes between these acids and cyclodextrins, as well as their in vivo evaluation on chemically induced skin cancer experimental models. In this study the synergistic activity of the acid mixture included inside hydroxypropyl-gamma-cyclodextrin (HPGCD) was monitored using in vitro tests and in vivo skin cancer models. The coefficient of drug interaction (CDI) was used to characterize the interactions as synergism, additivity or antagonism. Our results revealed an increased antitumor activity for the mixture of the two triterpenic acids, both single and in complex with cyclodextrin, thus proving their complementary biologic activities.

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“…Azithromycin accumulates and undergoes slow release in cells, especially in phagocytes, and thus has higher local concentration and longer half-life than older macrolides (i.e., erythromycin and clarithromycin) [ 1 , 2 ]. Recent studies have indicated that azithromycin could produce potent anti-proliferation effect by inducing apoptosis in HeLa cells and SGC-7901 cancer cells [ 3 ]. Clinical studies have suggested promising efficacy of azithromycin in combination with paclitaxel and cisplatin in stage III–IV NSCLC patients [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Azithromycin enhances anticancer activity of TRAIL by inhibiting autophagy and up‐regulating the protein levels of DR4/5 in colon cancer cells in vitro and in vivo

Qiao

Wang

Shang

et al. 2018

Cancer Communications

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BackgroundAzithromycin is a member of macrolide antibiotics, and has been reported to inhibit the proliferation of cancer cells. However, the underlying mechanisms are not been fully elucidated. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively targets tumor cells without damaging healthy cells. In the present study, we examined whether azithromycin is synergistic with TRAIL, and if so, the underlying mechanisms in colon cancers.MethodsHCT-116, SW480, SW620 and DiFi cells were treated with azithromycin, purified TRAIL, or their combination. A sulforhoddamine B assay was used to examine cell survival. Apoptosis was examined using annexin V-FITC/PI staining, and autophagy was observed by acridine orange staining. Western blot analysis was used to detect protein expression levels. In mechanistic experiments, siRNAs were used to knockdown death receptors (DR4, DR5) and LC-3B. The anticancer effect of azithromycin and TRAIL was also examined in BALB/c nude mice carrying HCT-116 xenografts.ResultsAzithromycin decreased the proliferation of HCT-116 and SW480 cells in a dose-dependent manner. Combination of azithromycin and TRAIL inhibited tumor growth in a manner that could not be explained by additive effects. Azithromycin increased the expressions of DR4, DR5, p62 and LC-3B proteins and potentiated induction of apoptosis by TRAIL. Knockdown of DR4 and DR5 with siRNAs increased cell survival rate and decreased the expression of cleaved-PARP induced by the combination of azithromycin and TRAIL. LC-3B siRNA and CQ potentiated the anti-proliferation activity of TRAIL alone, and increased the expressions of DR4 and DR5.ConclusionThe synergistic antitumor effect of azithromycin and TRAIL mainly relies on the up-regulations of DR4 and DR5, which in turn result from LC-3B-involved autophagy inhibition.Electronic supplementary materialThe online version of this article (10.1186/s40880-018-0309-9) contains supplementary material, which is available to authorized users.

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Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

Cited by 28 publications

References 37 publications

<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

The Synergistic Biologic Activity of Oleanolic and Ursolic Acids in Complex with Hydroxypropyl-γ-Cyclodextrin

Azithromycin enhances anticancer activity of TRAIL by inhibiting autophagy and up‐regulating the protein levels of DR4/5 in colon cancer cells in vitro and in vivo

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