Introduction-
The morbidity and mortality rates of malignant tumors continue to increase, becoming a major threat to human life. Tumor cells often become drug resistant, making it difficult to kill all tumor cells through chemotherapy and limiting curability, inevitably bringing about various side effects. While chemotherapeutic drugs inhibit or kill tumor cells, they also cause damage to normal tissues. These side effects seriously affect the tumor treatment effect and the quality of life of patients. Some phytochemicals like Epigallocatechin gallate (EGCG) have been reported to have chemosensitizing effects and to reduce the development of toxic side effects caused by chemotherapy.
EGCG, one of the most important active components of green tea, accounting for approximately 50–60% of catechin compounds, scavenges free radicals and reduces oxidative damage, which is not toxic to normal cells producing a positive effect on tumor prevention and treatment. In addition, EGCG has been reported to combat the drug resistance of cancer stem cells and enhance the sensitivity of chemotherapeutic drugs, thereby reducing the amount of drugs used, alleviating adverse side effects.
Fig. 1. Advantages of EGCG in adjuvant chemotherapy.
Research-
Enhanced Chemotherapy effects
EGCG on its own has strong anticancer activity, which is amplified when combined with chemotherapeutic agents for synergistic treatment. These mechanisms of action involve reduction of drug resistance in cancer stem cells, enhancement of chemotherapeutic drug sensitivity, induction of cell cycle arrest and apoptosis, inhibition of angiogenesis, and induction of anti-inflammatory and pro-oxidant effects.
Fig. 2. Mechanism of EGCG combined with chemotherapeutic drugs to enhance antitumor efficacy.
Attenuation of drug resistance in cancer stem cells(CSCs)- CSCs maintain self-renewal leading to tumor cells continuing to proliferate. In studies targeting CSCs, EGCG had a positive effect on CSC drug resistance, demonstrating strong inhibition of the growth and stemness of CSCs.
Enhancement of drug sensitivity- The combination of EGCG with chemotherapeutic drugs significantly reduces the IC50 value of chemotherapeutic drugs, while reducing the dosage of drugs can also significantly enhance the effect.
Cell cycle arrest induction- Combination therapy with EGCG and cisplatin induces cell cycle arrest in the G1 phase and enhances apoptosis in biliary tract cancer and NSCLC.
Reduction of Chemotherapy side effects-
Long-term use of chemotherapeutic drugs causes toxic side effects (gastrointestinal disorders, cardiotoxicity, nephrotoxicity, ototoxicity, neurotoxicity) in addition to drug resistance, limiting the effectiveness of the drugs.
Gastrointestinal disorders- Nausea, vomiting, loss of appetite caused due to inflammation of the gastrointestinal mucosa. EGCG ameliorates irinotecan-induced gastrointestinal side effects in mice by reducing oxidative damage
Nephrotoxicity- Cisplatin-induced nephrotoxicity due to an increase in oxidative stress and inflammatory cytokines in the kidney. EGCG reversed these changes, enhancing the activity of renal antioxidant enzymes and glutathione, reducing oxidative stress.
Ototoxicity- Damage to outer hair cells of the cochlea, spiral ganglia and stria vascularis (Cisplatin-induced). Oral administration of EGCG in rats attenuates hearing loss, reduces the loss of outer hair cells of the cochlea.
Limitations of adjuvant chemotherapy
EGCG and some chemotherapeutic drugs have certain antagonistic effect and reduce the effect of chemotherapy. Bortezomib is a proteasome inhibitor used clinically for the treatment of multiple myeloma. The boric acid component of bortezomib reacts with the catechol of EGCG to form cyclic boronic esters (Fig 3), leading to drug inactivation. The low oral bioavailability of EGCG is also a reason to limit its further application.
Fig. 3.A). Chemical structures of bortezomib and EGCG. B). Binding of bortezomib and EGCG. C). Bortezomib, EGCG, and Fe3+ nanomaterials rereleased under acidic conditions.
Nanomodification to enhance the chemotherapy effect
Nanoencapsulation technology has gained wide attention to improve the stability and bioavailability of EGCG. The nanomodification of EGCG with chemotherapeutic drugs not only exerts its own antitumor effect and alleviates the toxic side effects of chemotherapy but also enhances the stability, slows the release and enhances the pharmacokinetic parameters of the binary complex with the introduction of nanomaterials. It also has the advantages of low toxicity, tumor targeting and localization imaging ability.
Fig.4. Multiple beneficial effects of nanomaterials encapsulating chemotherapy drugs and EGCG.
Conclusion-
Although EGCG can enhance the therapeutic effects of chemotherapeutic drugs in many ways, there is still a lack of studies on the mechanism of action of EGCG and further pharmacological optimization at this stage. In conclusion, EGCG is a good adjuvant for chemotherapy; the use of nanotechnology to dual-load EGCG and chemotherapeutic agents for targeted tumor treatment increases the clinical application value of EGCG, highlighting EGCG treatment strategies as a promising research direction.
Reference-
Lin Wang, Penghui Li, Kun Feng,
EGCG adjuvant chemotherapy: Current status and future perspectives,
European Journal of Medicinal Chemistry,
Volume 250,
115197,
ISSN 0223-5234
DOI-
By Debangana Banerjee
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