Active Ingredients from Chinese Medicine for Combination Cancer Therapy

Abstract

Combination therapy against cancer has gained increasing attention because it can help to target multiple pathways to tackle oncologic progression and improve the limited antitumor effect of single-agent therapy. Chinese medicine has been studied extensively in cancer therapy and proven to be efficacious in many cases due to its wide spectrum of anticancer activities. In this review, we aim to summarize the recent progress of active ingredients from Chinese medicine (AIFCM) in combination with various cancer therapeutic modalities, including chemotherapy, gene therapy, radiotherapy, phototherapy and immunotherapy. In addition to highlighting the potential contribution of AIFCM in combination cancer therapy, we also elucidate the underlying mechanisms behind their synergistic effect and improved anticancer efficacy, thereby encouraging the inclusion of these AIFCM as part of effective armamentarium in fighting intractable cancers. Finally, we present the challenges and future perspectives of AIFCM combination therapy as a feasible and promising strategy for the optimization of cancer treatment and better clinical outcomes.

Keywords: Active ingredients; Chinese medicine; Combination cancer therapy; Nanomedicine.

Figure 1

The mechanism of active ingredients from Chinese medicine (AIFCM) in chemotherapy enhancement by inhibiting tumor proliferation, reversing multi-drug resistance and preventing cancer metastasis. Active ingredients from Chinese medicine: 1. Curcumin; 2. Genistein; 3. Baicalein; 4. Tetrandrine; 5. Triptolide; 6. β-elemene; 7. Paclitaxel; 8. Vincristine; 9. Camptothecin; 10. Arsenic trioxide; 11. Matrine; 12. Resveratrol; 13. Glaucine; 14. Nuciferine; 15. Andrographolide; 16. Ginsenoside; 17. Quercetin.

Figure 2

The combination therapy of curcumin and thioridazine for resistant human head and neck squamous cell carcinoma (AMC-HN4). (A) A scheme showing that the combination therapy downregulated the expression of c-FLIP and Mcl-1 via NOX4-mediated ROS production for restoring apoptosis. The synergistically induced (B) apoptosis and (C) ROS production by curcumin and thioridazine in AMC-HN4 cells. (D) The downregulation of c-FLIP and Mcl-1 induced by the combination therapy in NOX4-dependent manner. Reproduced from with permission from Elsevier.

Figure 3

The function and mechanism of AIFCM enhancing the therapeutic effect of gene therapy, radiotherapy and immunotherapy in combination therapy.

Figure 4

Combination of EGCG and CTGF siRNA for inhibition of resistant breast cancer. (A) Schematic illustration of the combination therapy for inhibiting CTGF-overexpressed breast cancer. (B) The enhanced cytotoxicity by the combined treatment in MDA-MB-231 cells. (C) Downregulation of drug resistance-associated proteins in MDA-MB-231 cells by the combination therapy. (D) The reduced tumor volume on xenografted mice by the combined treatment. Reproduced from with permission from American Chemical Society.

Figure 5

The anticancer mechanism of AIFCM combined with PTT, PDT, or PTT and PDT modalities for tumor therapy.

Figure 6

Combination of photothermal therapy and chemotherapy based on gamabufotalin and indomethacin. (A) A scheme showing the suppression of PTT-induced inflammatory response and chemotherapeutic sensitization effect by gamabufotalin and indomethacin via COX-2/PGE2 pathway. (B) The combination therapy down-regulated the PTT-induced pro-inflammatory cytokines (TNF-α and IL-6) of Hela cells. (C) The combined treatment inhibited the COX-2/PGE2 pathway and IKK/NF-κB pathway, and decreased the Bcl-2/Bax ratio in Hela cells. (D) The in vivo synergistic tumor inhibition by the combined treatment. Reproduced from with permission from Elsevier.

Figure 7

The combination of β-elemene and radiotherapy for radioresistant non-small-cell lung cancer treatment. (A) The illustration of β-elemene overcoming the radioresistance of A549 cells by suppressing the radiation-induced epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) transdifferentiation via the Prx-1/NF-κB/iNOS pathway. (B) The downregulation of EMT makers (N-cadherin and vimentin) and CSC markers (CD133, CD44, and epcam) by β-elemene in radiotherapy. (C) The combination therapy induced DNA damage, increased γ-H2AX (double-strand break marker) expression and decreased Rad51 (double-strand break repair protein) expression in A549 cells. (D) The enhanced therapeutic effect of β-elemene combined with radiotherapy in A549 xenograft mouse model. Reproduced from with permission from Zou et al.

Figure 8

The combination immunotherapy based on astragaloside III and photodynamic therapy (PDT) for the treatment of colon cancer. (A) Schematic illustration of synergistic immunotherapy mediated by the astragaloside III activated NK cells and the PDT activated T cells. (B) The combination therapy significantly reduced the tumor size and weight of CT26-tumor bearing mice. (C) The combined treatment showed improved ROS generation effect in CT26 cells. The synergistic immunotherapy promoted (D) NK cell activation and (E) CT26 cell inhibition effect. Reproduced from with permission from Elsevier.