CAPE was found to act both as radioprotector and radiosensitizer. Depending on the tissue type it can modulate the radiation response by following different mechanisms.
In the present study, we evaluated the radiomodulatory potential of caffeic acid phenethyl ester (CAPE), an active component of traditional herbal medicine propolis. CAPE has been identified as a potent anticancer agent in multiple cancer types and is reported to have the dual role of radioprotection and radiosensitization. However, the radiomodulatory potential of CAPE in prostate cancer (PCa), which eventually becomes radioresistant is not known. Therefore, we studied the effect of cotreatment of CAPE and gamma radiation on androgen-independent DU145 and PC3 cells. The combination treatment sensitized PCa cells to radiation in a dosedependent manner. The radiosensitizing effect of CAPE was observed in both cell lines. CAPE enhanced the level of ionizing radiation (IR)-induced gamma H2AX foci and cell death by apoptosis. The combination treatment also decreased the migration potential of PCa cells. This was confirmed by increased expression of E-cadherin and decrease in vimentin expression. CAPE sensitized PCa cells to radiation in vitro and induced apoptosis, augmented phosphorylation of Akt/mTOR, and hampered cell migration. At the mechanistic level, co-treatment of CAPE and IR inhibited cell growth by decreasing RAD50 and RAD51 proteins involved in DNA repair. This resulted in enhanced DNA damage and cell death. CAPE might represent a promising new adjuvant for the treatment of hormone-refractory radioresistant PCa.
Magnetic nanoparticle (MNP)-mediated magnetic hyperthermia
(MHT)
under an alternating magnetic field (AMF) causes tumor regression via reactive oxygen species (ROS) generation. However, less
therapeutic efficacy has been reported due to the generation of low
levels of ROS in a hypoxic tumor microenvironment. Therefore, improved
treatments are required to generate relatively high levels of ROS
to promote irreversible oxidative damage to the tumor cells. Herein,
we report a magnetothermodynamic (MTD) therapy, as a robust and versatile
approach for cancer treatment, by combining the magnetothermodynamic-related
ROS and heat-related immunological effect in order to overcome the
aforementioned obstacle. The synergistic therapy was achieved by the
development of vitamin k3 (Vk3)-loaded copper zinc ferrite nanoparticles
(Vk3@Si@CuZnIONPs) as an efficient MTD agent. The in vitro results unveiled that enhanced ROS production under the influence
of AMF is a predominant aspect in yielding an assertive anticancer
response. The in vivo antitumor response was assessed
in an ectopic tumor model of A549 lung adenocarcinoma by MTD. The
tumor inhibition rate of 69% was achieved within 20 days of MTD treatment,
exhibiting complete tumor eradication within 30 days. The validation
of antitumor response was marked by severe apoptosis (TUNEL, Caspase-3)
in the Vk3@Si@CuZnIONPs + AMF-treated group. The higher expression
level of heat shock proteins and proinflammatory cytokines (IL-6,
TNF-α, IL-1α, IL-1β) was speculated to play a role
in the activation of immune response for faster tumor regression in
the MTD-treated group. Therefore, by implementing a dual ROS and heat-mediated
immunogenic effect, the antitumor efficiency of future cancer magnetotherapies
will be greatly enhanced.
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