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Is Curcumin the Answer to Future Chemotherapy Cocktail?

ABSTRACT: The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure. The continuous use of conventional cancer therapies leads to chemoresistance, and a higher dose of treatment results in even greater toxicities among cancer patients. Therefore, the search for an alternative treatment modality is crucial to break this viscous cycle. This paper explores the suitability of curcumin combination treatment with other cancer therapies to curb cancer growth. We provide a critical insight to the mechanisms of action of curcumin, its role in combination therapy in various cancers, along with the molecular targets involved. Curcumin combination treatments were found to enhance anticancer effects, mediated by the multitargeting of several signalling pathways by curcumin and the co-administered cancer therapies. The preclinical and clinical evidence in curcumin combination therapy is critically analysed, and the future research direction of curcumin combination therapy is discussed.

SUBMITTER: Kong WY

PROVIDER: S-EPMC8303331 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Is Curcumin the Answer to Future Chemotherapy Cocktail?

Kong Wei-Yang WY Ngai Siew Ching SC Goh Bey-Hing BH Lee Learn-Han LH Htar Thet-Thet TT Chuah Lay-Hong LH

Molecules (Basel, Switzerland) 20210717 14

The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure. The continuous use of conventional cancer therapies leads to chemoresistance, and a higher dose of treatment results in even greater toxicities among cancer patients. Therefore, the search for ...[more]

PMID: 34299604

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Project description:Orthopedic device-related infection (ODRI) caused by Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA) biofilm may lead to persist infection and severe inflammatory osteolysis. Previous studies have demonstrated that both isobavachalcone and curcumin possess antimicrobial activity, recent studies also reveal their antiosteoporosis, anti-inflammation, and immunoregulatory effect. Thus, this study aims to investigate whether the combination of isobavachalcone and curcumin can enhance the anti-S. aureus biofilm activity of gentamicin and alleviate inflammatory osteolysis in vivo. EUCAST and a standardized MBEC assay were used to verify the synergy between isobavachalcone and curcumin with gentamicin against planktonic S. aureus and its biofilm in vitro, then the antimicrobial and immunoregulatory effect of cocktail therapy was demonstrated in a femoral ODRI mouse model in vivo by μCT analysis, histopathology, quantification of bacteria in bone and myeloid-derived suppressor cell (MDSC) in bone marrow. We tested on standard MSSA ATCC25923 and MRSA USA300, 5 clinical isolated MSSA, and 2 clinical isolated MRSA strains and found that gentamicin with curcumin (62.5-250 μg/ml) and gentamicin with isobavachalcone (1.56 μg/ml) are synergistic against planktonic MSSA, while gentamicin (128 μg/ml) with curcumin (31.25-62.5, 250-500 μg/ml) and gentamicin (64-128 μg/ml) with isobavachalcone (1.56-12.5 μg/ml) exhibit synergistic effect against MSSA biofilm. Results of further study revealed that cocktail of 128 μg/ml gentamicin together with 125 μg/ml curcumin +6.25 μg/ml isobavachalcone showed promising biofilm eradication effect with synergy against USA300 biofilm in vitro. Daily intraperitoneal administration of 20 mg/kg/day isobavachalcone, 20 mg/kg/day curcumin, and 20 mg/kg/day gentamicin, can reduce inflammatory osteolysis and maintain microarchitecture of trabecular bone during orthopedic device-related MRSA infection in mice. Cocktail therapy also enhanced reduction of MDSC M1 polarization in peri-implant tissue, suppression of MDSC amplification in bone marrow, and Eradication of USA300 biofilm in vivo. Together, these results suggest that the combination of isobavachalcone and curcumin as adjuvants administrated together with gentamicin significantly enhances its antimicrobial effect against S. aureus biofilm, and can also modify topical inflammation in ODRI and protect bone microstructure in vivo, which may serve as a potential treatment strategy, especially for S. aureus induced ODRI.

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Is Curcumin the Answer to Future Chemotherapy Cocktail?

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Is Curcumin the Answer to Future Chemotherapy Cocktail?

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